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Biomedical subjects

D Sage

Publications and source records attributed to D Sage.

18 recordsLinked to original sources
PubMed2005

Marrow transplants from matched unrelated donors for aplastic anaemia using alemtuzumab, fludarabine and cyclophosphamide based conditioning.

Graft failure, regimen-related toxicity and graft-versus-host disease (GVHD) are the critical barriers to unrelated donor transplants for aplastic anaemia (AA). We investigated the use of a novel conditioning regimen consisting of alemtuzumab (humanized CD52 antibody), fludarabine and cyclophosphamide in seven patients with AA, who underwent bone marrow transplant procedure using matched unrelated donors. The aetiology of AA was acquired (n=3), Fanconi's (n=3) and congenital (n=1). Median age was 13 years (range 8-35). All the donors were fully matched for HLA class I and II antigens using high-resolution typing. All the patients engrafted at a median of 18 days (range 13-35). Two patients died of transplant-related complications: one of adenovirus disease and the other developed extensive chronic GVHD of skin followed by cytomegalovirus (CMV) disease. Three patients developed Grade II acute GVHD disease (GVHD); none had Grade III-IV acute GVHD. Of the six evaluable patients, only one developed chronic GVHD. We conclude that this conditioning regimen for unrelated donor transplants for AA is sufficiently immunosuppressive to allow stable engraftment and appears to have a favourable impact on the incidence and severity of GVHD, warranting further investigation.

Adolescent↗
PubMed2005

Diagnosis of transfusion-associated graft-vs.-host disease: the importance of short tandem repeat analysis.

Transfusion-associated graft-vs.-host disease (TA-GvHD) can occur following transfusion of blood products containing immunocompetent lymphocytes, usually from HLA homozygous donors, into immunocompromised patients sharing one HLA haplotype with the donor. The diagnosis of TA-GvHD may be delayed due to the initial nonspecific clinical features involved. Investigations to detect the presence of donor-derived cells in the blood and/or affected tissues of the recipient are essential to confirm the diagnosis. We report the investigation of suspected TA-GvHD using short tandem repeat (STR) analysis, to detect the presence of donor cells (chimerism), in an immunocompetent patient admitted for coronary artery bypass surgery. Peripheral blood and skin biopsies (from affected and nonaffected sites) from the patient and peripheral blood samples from the implicated donors were taken for HLA typing and STR analysis. STR analysis revealed the presence of donor material in the patient's peripheral blood sample and in DNA extracted from the affected skin biopsy but not the unaffected biopsy, suggesting lymphocytes from this donor were responsible for the development of TA-GvHD. Furthermore, HLA typing results supported the diagnosis of TA-GvHD. These data demonstrate the use of STR and HLA analysis as effective tools in the diagnosis of TA-GvHD.

Aged↗
PubMed2005

Vitamin A is a necessary factor for sympathetic-independent rhythmic activation of mitogen-activated protein kinase in the rat pineal gland.

The circadian clock in the suprachiasmatic nucleus (SCN) controls day-to-day physiology and behavior by sending timing messages to multiple peripheral oscillators. In the pineal gland, a major SCN target, circadian events are believed to be driven exclusively by the rhythmic release of norepinephrine from superior cervical ganglia (SCG) neurons relaying clock messages through a polysynaptic pathway. Here we show in rat an SCN-driven daily rhythm of pineal MAPK activation that is not dependent on the SCG and whose maintenance requires vitamin A as a blood-borne factor. This finding challenges the dogma that SCG-released norepinephrine is an exclusive mediator of SCN-pineal communication and allows the assumption that humoral mechanisms are involved in pineal integration of temporal messages.

Adrenergic Fibers↗
PubMed2002

Autologous recovery following non-myeloablative unrelated donor bone marrow transplantation for severe aplastic anaemia.

We report the outcome of nine unrelated bone marrow transplants performed for acquired severe aplastic anaemia at a single centre. Six patients received transplants from fully matched donors. Three donor/recipient pairs were mismatched, two at a single allele on high resolution typing. Pre-transplant conditioning consisted of cyclophosphamide and in vivo Campath-1 monoclonal antibody. One patient also received total body irradiation (TBI), and another patient with a coexisting paroxysmal nocturnal haemoglobinuria (PNH) clone received additional busulphan. Cyclosporin A was given for 12 months as prophylaxis against graft-versus-host disease (GVHD). Six of nine patients are alive and transfusion independent with a mean follow-up of 24 months (range: 1.5-94). All six patients who received fully matched transplants are alive; the three who received mismatched grafts died. Four long-term survivors developed autologous haematological recovery following rejection of their grafts. Acute GVHD grade II+ occurred in two patients. We highlight the importance of high-resolution HLA typing, including Cw matching in reducing the incidence of graft rejection and GVHD, resulting in improved survival in our patient group. This study also shows that autologous recovery with long-term survival can occur following non-irradiation conditioning regimens.

Adolescent↗
PubMed2001

Postnatal maternal deprivation produces long-lasting modifications of the stress response, feeding and stress-related behaviour in the rat.

The hypothalamo-pituitary-adrenal (HPA) axis plays a central role both in the regulation of the stress response, and in the control of feeding behaviour. Sensitivity of the HPA axis to respond to stress varies both during ontogeny and between individuals, and can be altered by neonatal events. The aim of our experiments was to determine whether early events that affect the HPA axis could also induce persistent modifications in food intake (quantitatively and qualitatively), as well as alterations of anxiety-related behaviour. Twenty-four-hour maternal deprivation was introduced at two different periods of HPA maturation, on day 5 (DEP5) or day 14 (DEP14) after birth. Sequential measurements of plasma levels of adrenocorticotropin hormone (ACTH) and corticosterone showed that this deprivation altered the HPA axis of adults; the response to restraint stress was prolonged in DEP5 and a higher ACTH peak appeared in DEP14. The neonatal stress also produced long-lasting modifications of rat behaviour, as DEP14 adults became more anxious. Standard food intake decreased in both groups of deprived rats. Diet preferences also changed, as carbohydrate intake decreased in DEP5 rats. Corticosteroid receptor binding did not vary in the hippocampus of the deprived rats. The modifications of the stress response and the behaviour parameters could be due to the alteration of corticosteroid receptors in the hypothalamic paraventricular nucleus and/or corticotropin-releasing hormone or vasopressin function, but these parameters have yet to be determined. This early stress paradigm altering feeding behaviour could become an interesting model for research into human eating disorders.

Adrenocorticotropic Hormone↗
PubMed2001

Recurrent transfusion-related acute lung injury.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a rare condition that is commonly associated with the transfusion of donor plasma containing WBC antibodies. Biologically active lipids that accumulate during storage of RBCs and platelets may also cause TRALI. There has been only one previously reported case of recurrent TRALI. CASE REPORT: A patient received a transfusion 2 days after undergoing hysterectomy; she developed TRALI after receiving the transfusion. The patient recovered after being on ventilation for 6 days but received an additional transfusion and had a second episode of TRALI, which required further ventilation. RESULTS: Laboratory investigation of the first episode of TRALI suggested the presence of HLA-A2 (N = 1) and granulocyte-specific IgM antibodies (N = 2) in the sera from three of the donors. All three sera reacted in crossmatch studies with the patient's granulocytes and lymphocytes. Lymphocyte-specific IgG antibodies were detected in the patient's serum. There was no evidence to suggest the involvement of WBC antibodies in the second episode of TRALI. Antibody screening of the donors' samples and both forward and reverse crossmatch studies were negative. CONCLUSION: The first episode of TRALI seems to be due to the action of HLA-A2 and granulocyte-specific IgM antibodies. The second episode may have been due to the action of lipid neutrophil-priming agents in the donors' units in association with the patient's underlying pulmonary condition (i.e., recovering from lung injury). TRALI can recur if a patient requires further transfusion support shortly after an initial episode of TRALI.

Acute Disease↗
PubMed2001

Involvement of the suprachiasmatic nucleus in diurnal ACTH and corticosterone responsiveness to stress.

We explored the contribution of the suprachiasmatic nucleus (SCN) in ACTH and corticosterone (CORT) diurnal responsiveness of the rat to restraint stress applied either in the morning (AM) or in the evening (PM). Ablation of the SCN caused the diurnal rhythmicity of the CORT response to disappear but had no effects on AM vs. PM differences in the ACTH response. Stress-response curves in SCN-lesioned rats that had prestress levels of CORT either in the AM range or in the PM range, when compared with those obtained for AM and PM controls, showed that the SCN differentially regulates the stress response depending on the underlying secretory activity of the adrenal cortex. When basal CORT secretion is at its lowest, the SCN inhibits CORT responsiveness to stress by controlling pituitary corticotrophs; but when it is at its highest, it has a permissive action that will bypass the hypophysis and reach the adrenals to adjust the response of the gland to ACTH.

Adrenocorticotropic Hormone↗
PubMed2000

Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomised trials.

OBJECTIVES: To obtain reliable estimates of the effects of neuraxial blockade with epidural or spinal anaesthesia on postoperative morbidity and mortality. DESIGN: Systematic review of all trials with randomisation to intraoperative neuraxial blockade or not. STUDIES: 141 trials including 9559 patients for which data were available before 1 January 1997. Trials were eligible irrespective of their primary aims, concomitant use of general anaesthesia, publication status, or language. Trials were identified by extensive search methods, and substantial amounts of data were obtained or confirmed by correspondence with trialists. MAIN OUTCOME MEASURES: All cause mortality, deep vein thrombosis, pulmonary embolism, myocardial infarction, transfusion requirements, pneumonia, other infections, respiratory depression, and renal failure. RESULTS: Overall mortality was reduced by about a third in patients allocated to neuraxial blockade (103 deaths/4871 patients versus 144/4688 patients, odds ratio=0.70, 95% confidence interval 0.54 to 0.90, P=0. 006). Neuraxial blockade reduced the odds of deep vein thrombosis by 44%, pulmonary embolism by 55%, transfusion requirements by 50%, pneumonia by 39%, and respiratory depression by 59% (all P<0.001). There were also reductions in myocardial infarction and renal failure. Although there was limited power to assess subgroup effects, the proportional reductions in mortality did not clearly differ by surgical group, type of blockade (epidural or spinal), or in those trials in which neuraxial blockade was combined with general anaesthesia compared with trials in which neuraxial blockade was used alone. CONCLUSIONS: Neuraxial blockade reduces postoperative mortality and other serious complications. The size of some of these benefits remains uncertain, and further research is required to determine whether these effects are due solely to benefits of neuraxial blockade or partly to avoidance of general anaesthesia. Nevertheless, these findings support more widespread use of neuraxial blockade.

Anesthesia, Epidural↗
PubMed2000

Glucocorticoids up-regulate the expression of glial fibrillary acidic protein in the rat suprachiasmatic nucleus.

Immunoreactivity against glial fibrillary acidic protein (GFAP) was used as a dynamic index in adrenalectomized rats subjected or not to corticosterone replacement to investigate whether glucocorticoids may interact with astrocytes in the suprachiasmatic nucleus (SCN), the master component of the central circadian clock. GFAP staining in the SCN was significantly higher in rats having received implants that restored physiological plasma levels of corticosterone within diurnal or nocturnal limits than in non-normalized rats. The effects of corticosterone were similar in the parvocellular portion of the paraventricular nucleus but were opposite in the hippocampus, another major site of negative feed-back regulation of the hypothalamic-pituitary-adrenal axis, where a decreased GFAP staining was observed in discrete regions of the dentate gyrus. This indicates that glucocorticoids may positively or negatively regulate GFAP, depending on the target brain structure. In the SCN, that contains only few if any glucocorticoid receptors, indirect mechanisms that may involve serotoninergic neurons are probably responsible for the effects of corticosterone level. It is proposed that the corticosterone-induced increase in GFAP staining in that nucleus accounts for dynamic changes in neurone-astrocyte interactions that might occur in relation with natural fluctuations of glucocorticoids over the 24 h period.

Adrenalectomy↗
PubMed2000

Circadian binding activity of AP-1, a regulator of the arylalkylamine N-acetyltransferase gene in the rat pineal gland, depends on circadian Fra-2, c-Jun, and Jun-D expression and is regulated by the clock's zeitgebers.

The daily rhythm in circulating melatonin is driven by a circadian rhythm in the expression of the arylalkylamine N:-acetyltransferase gene in the rat pineal gland. Turning off expression of this gene at the end of night is believed to involve inhibitory transcription factors, among which Fos-related antigen 2 (Fra-2) appears as a good candidate. Circadian rhythms in the expression of three proteins of activating protein-1 (AP-1) complexes, namely, Fra-2, c-Jun, and Jun-D, are shown here to account for circadian variations in AP-1 binding activity. Quantitative variations in the Fra-2 component over the circadian cycle were associated with qualitative variations in protein isoforms. Destruction of the suprachiasmatic nucleus resulted in decreased nocturnal AP-1 activity, showing that AP-1 circadian rhythm is driven by this nucleus. Exposure to light during subjective night and administration of a serotonin 5-HT(1A)/5-HT(7) receptor agonist during subjective day, respectively, induced a 50% decrease and a 50% increase in both AP-1 and Fra-2 expression. These effects were impaired by suprachiasmatic nucleus lesions. These data show that pineal AP-1 binding activity, which results from Fra-2 expression, can be modulated by light and serotonin through the suprachiasmatic nucleus according to a "phase dependence" that is characteristic of the rhythm of clock sensitivity to both zeitgebers.

Analysis of Variance↗
PubMed1999

A comparison of the impact of hospital reform on medical subcultures in some Australian and New Zealand hospitals.

This article examines similarities and differences in the way that hospital staff in Australia and New Zealand are evaluating efforts to improve quality, clinical effectiveness and service integration, and to strengthen clinical accountability. We draw on data from a cross-national study of hospital staff in Australia and New Zealand. The results highlight the way in which respondents' views about reform are influenced by the interplay of two factors: the impact of respondents' occupational backgrounds (our findings point to differences in the profession-based subcultures of medicine, nursing and general management and the way that these are reflected in respondents' assessments of particular aspects of reform); and the way that the impact of professional subcultures may be mitigated by differences between the systems in which respondents were located, including differences between the programs of reform that have been pursued in each country. The implications of these findings are discussed.

Australia↗
PubMed1996

Attitudes and practices of New Zealand anaesthetists with regard to epidural and subarachnoid anaesthesia.

A survey was conducted among 259 New Zealand specialist anaesthetists to assess attitudes and practices with regard to epidural or subarachnoid anaesthesia (ESA). Ninety-four per cent replied and virtually all of the respondents indicated that they performed ESA at some time. ESA was used by most anaesthetists for most patients undergoing major hip or knee surgery, abdomino-perineal resection, cystectomy, caesarean section or transurethral resection of the prostate, ESA was used is about half of patients undergoing abdominal aortic aneurysm repair, femoro-popliteal bypass or thoracotomy and there was marked variation between anaesthetists in the frequency of using ESA for these procedures. There was broad consensus about the importance of a number of factors that might influence the decision to employ ESA; in particular that systemic sepsis and prolonged bleeding time were important contraindications and that patient preference and chronic lung disease were important indications. However respondents were equally divided as to whether they felt that recent myocardial infarction or congestive heart failure constituted indications or contraindications to ESA.

Anesthesia, Epidural↗
PubMed1993

Covalent linking of haptens, proteins and nucleic acids to a modified polystyrene support.

Biological molecules of various molecular weights were successfully linked to polystyrene microtitration plates bearing carbonyl and hydroxyl reactive groups. Cross-linking of proteins, nucleic acids and haptens was carried out with water soluble carbodiimide. The covalent nature of the binding reaction was demonstrated by the immunodetection of a hapten linked to the surface through a disulphide spacer arm and its subsequent release by cleavage of the bridge. The amount of protein fixed per surface unit could be correlated to molecular weight. Nanograms of biotinylated nucleic acids and synthetic polynucleotides could also be retained on the solid support.

Enzyme-Linked Immunosorbent Assay↗
PubMed1989

[Rapid collection of swine lymphocyte subpopulations in large quantity].

Lymphocyte subpopulations derived from different pig organs (blood, spleen, mesenteric lymph nodes) were separated by a simple, rapid and cheap panning technique, using either normal or ozone treated Petri dishes with bovine serum albumin. Slg+ lymphocytes could thus be obtained with a purity of up to 95% by adhesion onto Corning plastic dishes. The purified cells retained their proliferative activity with regard to lectins. The subpopulation including PT4 and PT8 was then separated by another panning on ozone-treated plastic dishes with a purity of 80-90%.

Animals↗
PubMed1981

Intradermal drug testing following anaphylactoid reactions during anaesthesia.

Intradermal testing of intravenous anaesthetic drugs was performed on 34 patients following acute anaphylactoid reactions during anaesthesia. Twenty-three patients had positive skin tests and 18 of these were positive for a single drug. Muscle relaxants were the drugs implicated most commonly. Intradermal testing is safe and provides useful and often specific positive information, but false-negative results probably occur.

Adolescent↗
PubMedDate not supplied

The unequal equation.

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Health Services Accessibility↗