bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatopulmonary syndrome: a concern for the anesthetist? Pre‐operative evaluation of hypoxemic patients with liver disease
Authors: Mazzeo A. T. , Lucanto T. , Santamaria L. B.
Published: January 2004

Liver cirrhosis and other chronic hepatic diseases are followed in a subset of affected patients by gas exchange abnormalities resulting from a syndrome called hepatopulmonary syndrome (HPS). The structural basis of this clinical entity is an alteration of pulmonary vasculature resulting in abnormal vasodilatation and mismatching of ventilation and perfusion of the lung. Dilatation of the capillary bed near the gas exchange area is the most important factor implicated; it precludes O2 molecules diffusing to the centrum of the dilated vessels to oxygenate venous blood. Contrast (microbubbles) echocardiography and lung perfusion scan are, respectively, the screening tests with the highest sensitivity and specificity for HPS diagnosis. Because of the high morbidity and mortality of HPS, clinicians have been trying to understand the pathophysiology of pulmonary vasodilatation in the hope that the process can be reversed pharmacologically or surgically. An imbalance between production and clearance of vasoactive circulating substances has been implicated in the pathogenesis of HPS with glucagon and nitric oxide among the principal responsible factors. To date various molecules have been implicated for therapy but without definitive positive results. Liver transplantation remains the only real therapy for HPS, and resolution of gas exchange defects outlines the possible functional reversible nature of vascular abnormalities of this syndrome. The need to perform surgery under general anesthesia for hepatic and extrahepatic procedures in patients with HPS is followed by an increased peri‐operative risk. The authors emphasize the role of pre‐operative clinical evaluation for proper patient management during the peri‐operative period.
The angiotensin II receptor blocker candesartan improves survival and mesenteric perfusion in an acute porcine endotoxin model
Authors: Laesser M. , Oi Y. , Ewert S. , Fändriks L. , Åneman A.
Published: January 2004

Background:  Blockade of the angiotensin II type 1 (AT1) receptor has been demonstrated to ameliorate splanchnic hypoperfusion in acute experimental circulatory failure. This study focused on hemodynamic changes and survival in pigs treated with AT1 blockade prior to or during acute endotoxinemia.

Methods:  Escherichia coli lipopolysaccharide endotoxin was infused in anesthetized and mechanically ventilated pigs. Systemic, renal, mesenteric and jejunal mucosal perfusion as well as systemic oxygen and acid‐base balance were monitored. The selective AT1 receptor blocker candesartan was administered prior to as well as during endotoxinemia. Control animals received the saline vehicle.

Results:  Pre‐treatment with candesartan resulted in higher survival rate (83%, 10 out of 12 animals) compared with 50% (6 of 12) in control animals and 27% (3 of 11) in animals treated during endotoxinemia. Pre‐treatment with candesartan resulted in higher cardiac output, mixed venous oxygen saturation, arterial standard base‐excess, portal venous blood flow during endotoxin infusion compared with controls and animals treated during endotoxinemia. No adverse effects were found on neither systemic nor renal circulation.

Conclusion:  The favorable results of AT1 receptor blockade prior to endotoxinemia are lost when blockade is established during endotoxinemia demonstrating the importance of the renin‐angiotensin system and its dynamic involvement in acute endotoxinemic shock.
Seizures in a 77‐year‐old‐woman after a bolus dose of remifentanil
Authors: Nielsen J. , KrØigaard M.
Published: January 2004

Seizures in patients with no history of epilepsy has been associated with administration of remifentanil in two previous case reports. We present a case where a bolus dose of remifentanil (50 micrograms/kg) was followed by a self terminating generalised tonic‐clonic seizure in a patient admitted for acute hip surgery, and no previous history of epilepsy.
Effect of desflurane/remifentanil anaesthesia on glucose metabolism during surgery: a comparison with desflurane/epidural anaesthesia
Authors: Schricker T. , Galeone M. , Wykes L. , Carli F.
Published: January 2004

Background:  The aim of this study was to investigate the effect of general anaesthesia combined with remifentanil or epidural blockade on glucose metabolism during surgery.

Methods:  We randomly assigned patients undergoing elective colorectal surgery to receive either desflurane anaesthesia supplemented with intravenous remifentanil (n = 7) or desflurane anaesthesia supplemented with epidural bupivacaine (n = 7). Plasma concentrations of glucose, lactate, free fatty acids (FFA), insulin, glucagon and cortisol were measured before and after 2 h of surgery. Pre‐ and intraoperative whole body glucose production and glucose clearance, an indicator of glucose uptake, were determined by an isotope dilution technique using [6,6–2H2]glucose.

Results:  In both groups intraoperative glucose production ( P< 0.05) and uptake ( P< 0.05) decreased. Plasma glucose concentrations ( P< 0.05) increased during surgery but did not exceed the normal range (remifentanil group: 5.7 ± 0.7 mmol l−1, epidural group: 5.8 ± 0.4 mmol l−1). The plasma concentrations of lactate, FFA, insulin and glucagon remained unchanged during the operation. The plasma cortisol concentration in both groups increased intraoperatively (P< 0.05).

Conclusion:  Both desflurane/remifentanil and desflurane/epidural anaesthesia decrease the intraoperative rate of whole body glucose production, thereby attenuating the hyperglycaemic response to colorectal surgery.
Are there reliable predictors of postoperative pain?
Authors: Mamie C. , Bernstein M. , Morabia A. , Klopfenstein C. E. , Sloutskis D. , Forster A.
Published: January 2004

Background:  The purpose of this study was to identify the preoperative determinants of severe postoperative pain.

Methods:  Potential predictors were assessed using a questionnaire submitted on the day before surgery. Pain at rest, and pain during coughing/mobilization, were measured using visual analog scales on the day of surgery and on the following 2 days. The type of postoperative pain management was not standardized and was prescribed by the anesthesiologist in charge. Multivariate logistic regression models explaining postoperative pain were developed in Group I, comprising 304 consecutive patients undergoing orthopedic or intraperitoneal surgery, and validated in Group II, comprising 145 independent patients.

Results:  Of the 62 variables examined by univariate analysis, only five were found to increase the risk of severe postoperative pain in Group I at rest and six factors during cough/mobilization. In the multivariate model for pain at rest, general anesthesia, expectation of postoperative pain, and chronic sleeping difficulties increased the risk of severe postoperative pain. In Group II, only chronic sleeping difficulties remained (OR: 3.97, 95% Cl: 1.69–9.29). In the multivariate model during cough/mobilization, intraperitoneal surgery, fear of postoperative pain, and having a relative with a history of pain increased the risk of severe postoperative pain in Group I. Intraperitoneal surgery OR 2.45 (95% Cl = 1.01–4.50) and having a relative with a history of pain OR 2.06 (95% Cl = 1.005–4.50) remained in Group II.

Conclusion:  Of the many factors that may influence postoperative pain, chronic sleeping difficulties emerge in this population of patients as the strongest determinant of pain at rest. Intraperitoneal surgery and having a relative with a history of pain are the strongest determinants of pain during cough/mobilization. These findings make physiological sense and deserve more attention by anesthesiologists.
Phagocytosis of opsonized apoptotic cells: roles for ‘old-fashioned’ receptors for antibody and complement
Authors: HART S P , SMITH J R , DRANSFIELD I
Published: January 2004

Efficient phagocytic clearance of apoptotic cells is crucial in many biological processes. A bewildering array of phagocyte receptors have been implicated in apoptotic cell clearance, but there is little convincing evidence that they act directly as apoptotic cell receptors. Alternatively, apoptotic cells may become opsonized, whereby naturally occurring soluble factors (opsonins) bind to the cell surface and initiate phagocytosis. Evidence is accumulating that antibodies and complement proteins opsonize apoptotic cells, leading to phagocytosis mediated by well-defined ‘old-fashioned’ receptors for immunoglobulin-Fc and complement. In this review we summarize the evidence that opsonization is necessary for high capacity clearance of apoptotic cells, which would render putative direct apoptotic cell receptors redundant.
High dose interleukin-12 exacerbatesBordetella pertussisinfection and is associated with suppression of cell-mediated immunity in a murine aerosol challenge model
Authors: CARTER C R D , DAGG B M , WHITMORE K M , KEEBLE J R , ASOKANATHAN C , XING D , WALKER K B
Published: January 2004

The in -vivo clearance of Bordetella pertussis infections in murine models in naive mice and animals vaccinated with whole-cell vaccine is considered to be via a Th-1-dependent mechanism in which interleukin-12 (IL)-12 may play a prominent role. It has also been demonstrated clearly that the treatment of animals with macrophage-derived IL-12 administered with an acellular vaccine can increase the efficacy of this vaccine preparation to levels seen with the whole-cell vaccine. However, the effects of exogenously added IL-12 on immune responses in non-vaccinated B. pertussis-challenged mice remain unclear, with two studies giving contradictory findings. In this study we have treated mice with escalating doses of mIL-12 (0·1–10 µg/mouse) prior to challenge with B. pertussis (using an aerosol challenge model of infection). The ability of mice to clear infection was assessed in IL-12 treated and in phosphate buffered saline (PBS) control animals at days 6 and 13 post-challenge. Lymphoid cells were isolated from spleen and cell-mediated immune responses assessed at days 1, 6 and 13 post-challenge. In addition, the direct effects of high-dose IL-12 on challenged mice was assessed by checking natural killer (NK) activity from isolated lung and spleen lymphoid cells as well as interferon-γ (IFN-γ) generation from isolated cells and serum at day 1 post-challenge. The results from this study show that bacterial colonization of the lungs is actually enhanced following treatment with high-dose IL-12. This is associated with impaired cellular immune responses. The mechanisms associated with the immunosuppressive effects of IL-12 are discussed.
Generation of B220low B cells and production of autoantibodies in mice with experimental amyloidosis: association of primordial T cells with this phenomenon
Authors: KAWABE S , ABE T , KAWAMURA H , GEJYO F , ABO T
Published: January 2004

To investigate the immunological state in amyloidosis, mice were twice intraperitoneally injected (2-week interval) with casein emulsified in complete Freund's adjuvant. Two weeks after the treatment, amyloid deposits were detected in the spleen and other organs of these mice. The number of lymphocytes yielded by the liver and spleen increased significantly. The most affected lymphocyte subset was found to be B cells, namely, the total number of B cells increased and unusual B220low B cells were newly generated in the liver and spleen. In other words, not only normal B220high B cells but also unusual B220low B cells were detected in these organs of mice with amyloidosis. In parallel with this phenomenon, autoantibodies against denatured DNA were detected in sera. Since such autoantibodies are known to accompany the functional activation of NKT cells, NKT cell-deficient mice were used for the induction of amyloidosis. Such mice showed less formation of amyloidosis and lower levels of autoantibodies in sera. Athymic nude mice were NKT cell-deficient but NK1·1–TCRint cells were present. These athymic mice showed an intermediate induction of amyloidosis. The cytokine profile seen in mice with amyloidosis was the Th0 type, showing simultaneous production of IL-4 and IFNγ. These results suggest that the generation of B220low B cells and the production of autoantibodies in aid of primordial T cells may be major immunological mechanisms in amyloidosis mice.
Blocking B7 and CD40 co-stimulatory molecules decreases antiviral T cell activity
Authors: VERMEIREN J , CEUPPENS J L , HAEGEL-KRONENBERGER H , DE BOER M , BOON L , VAN GOOL S W
Published: January 2004

Inhibition of co-stimulatory signals for T cells by interrupting CD80/CD86–CD28 and CD40–CD154 interactions is a promising approach to prevent transplant rejection and to induce graft tolerance. However, this tolerizing treatment might affect T cell reactivity towards all the antigens to which the immune system is exposed during treatment. We addressed the question whether such inhibition of co-stimulatory ligands on human antigen presenting cells (APC) would affect T cell reactivity against a virus. This was tested in an in vitro system with freshly isolated human monocytes transduced with adenovirus (ad) containing either murine interferon-γ (mIFN-γ) or green fluorescent protein (GFP) as marker transgene. T cells co-cultured with transduced monocytes proliferated and produced cytokines. These ‘primed’ T cells had strong antiviral activity as they subsequently killed ad/GFP-transduced monocytes and reduced mIFN-γ accumulation in coculture with ad/mIFN-transduced monocytes. However, if priming had occurred in the presence of blocking anti-CD40/CD80/CD86 MoAbs, generation of this antiviral activity was completely prevented. Moreover, T cells primed in the absence of co-stimulatory cells failed to proliferate upon restimulation with adenovirus-transduced monocytes. The results confirm that co-stimulatory signals from APC are required for efficient induction of antiviral T cell activity and point to a potential infectious risk of blocking co-stimulatory signals.
Dietary soy phytoestrogens and ERαsignalling modulate interferon gamma production in response to bacterial infection
Authors: CURRAN E M , JUDY B M , NEWTON L G , LUBAHN D B , ROTTINGHAUS G E , MACDONALD R S , FRANKLIN C , ESTES D M
Published: January 2004

Diets rich in soy phytoestrogens have many potential health benefits but isoflavones such as genistein may suppress cell mediated immune function. The effect of dietary phytoestrogens on the host response to infection has not been extensively examined. Mice were fed a diet containing soy phytoestrogens and infected with Mycobacterium avium to establish a chronic infection and inflammatory response. As phytoestrogens may act through classical oestrogen receptors (ER), mice deficient in ERα signalling and wild type mice were evaluated for a panel of Type 1-associated cytokines (IFNγ, IL-12 and IL-18) in the spleen. IFNγ production in the spleen was increased approximately 4-fold in ERα-deficient mice fed a casein-based diet over wild type mice fed a casein-based diet (P < 0·05), suggesting a role for ERα in suppressing IFNγ production. IL-18 levels in spleens of wild type mice were decreased compared to ERα-deficient mice on a casein diet. Splenic IL-12 and IL-18 levels were not affected in wild type and ERα-deficient mice on the phytoestrogen containing diets, with the exception that whole soy increased IL-12 levels in the tissues of ERα deficient mice. We conclude that ERα and dietary phytoestrogens can influence production of key regulatory cytokines in response to chronic bacterial infection.
Endotoxin stimulates monocyte–endothelial cell interactions in mouse intestinal Peyer's patches and villus mucosa
Authors: ISHII N , TSUZUKI Y , MATSUZAKI K , MIYAZAKI J , OKADA Y , HOKARI R , KAWAGUCHI A , NAGAO S , ITOH K , MIURA S
Published: January 2004

Although monocyte–endothelial cell interactions represent an initial step in controlling the recruitment of monocytes in inflamed tissues, their dynamic processes in microvessels of lymphoid (Peyer's patches) and non-lymphoid (villus) regions in gut-associated lymphoid tissue remain poorly understood. We monitored the migration of fluorescence-labelled monocytes derived from the spleen in intestinal microvessels with or without lipopolysaccharide (LPS) treatment and investigated the role of adhesion molecules, P-selectin, vascular cell adhesion molecule (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). In control mice, there were few interactions between infused monocytes and the endothelium of intestinal microvessels. The monocyte–endothelial interactions (both rolling and adhesion) were significantly increased in intestinal microvessels of LPS-treated mice compared with those in controls. Anti-P-selectin monoclonal antibody (MoAb) significantly suppressed the LPS-induced increase in monocyte rolling in postcapillary venules of Peyer's patches and submucosal venules. Anti-VCAM-1 MoAbs significantly suppressed the LPS-induced increase in monocyte adhesion to postcapillary venules (PCVs) of Peyer's patches, submucosal venules, and villus capillaries. In contrast, anti-ICAM-1 MoAb significantly suppressed the number of adherent monocytes in PCV of Peyer's patches but not in submucosal venules or villus capillaries. These observations demonstrated that LPS treatment resulted in a significant increase in recruitment of monocytes both in microvessels of lymphoid and non-lymphoid regions and that P-selectin, VCAM-1 and ICAM-1 appeared to play important roles in LPS-induced interactions.
Desferrioxamine modulates chemically induced T helper 2-mediated autoimmunity in the rat
Authors: WU Z , HOLWILL S D J , OLIVEIRA D B G
Published: January 2004

A rise in interleukin (IL) 4-dependent immunoglobulin E (IgE) is a hallmark of the mercuric chloride (HgCl2)-induced Th2-mediated autoimmune syndrome in the Brown Norway (BN) rat, and one of the mediators in allergic asthma in human. Oxidative stress, a potential factor related to the pathogenesis of allergy and asthma, has been shown to up-regulate IL-4 in mast cells and predispose to degranulation in vitro. However, it remains unknown whether oxidative/antioxidative imbalance plays a role in this Th2-driven model of autoimmunity in the rat. Here we show that administration of the non-sulphydryl-containing antioxidant desferrioxamine i.p. and s.c. to BN rats reduces HgCl2-enhanced IL-4 gene expression and inhibits HgCl2-induced Th2-mediated autoimmunity. Desferrioxamine treatment suppresses significantly IgE production and lymphoproliferation, and reduces tissue injury in the form of caecal vasculitis in the HgCl2-induced autoimmune syndrome. These results support a role for oxidative stress in the pathogenesis of the HgCl2-induced Th2-dominated autoimmune syndrome. This finding might have implications for understanding the mechanisms involved in Th2 cell responses as seen in allergy and asthma and thereby aid the development of new therapeutic strategies for these diseases.
Mycobacterial heat shock protein 70 induces interleukin-10 production: immunomodulation of synovial cell cytokine profile and dendritic cell maturation
Authors: DETANICO T , RODRIGUES L , SABRITTO A C , KEISERMANN M , BAUER M E , ZWICKEY H , BONORINO C
Published: January 2004

Cytokines are key modulators of the immune responses that take place in the inflamed synovium of arthritis patients. Consequently, substances that can reverse the inflammatory profile of the inflamed joint are potential tools for clinical management of the disease. Mycobacterial heat shock protein 70 (MTBHSP70) has been found to protect rats from experimentally induced arthritis through the induction of interleukin (IL)-10-producing T cells. In this study, we have demonstrated that MTBHSP70 induces IL-10 production in synoviocytes from arthritis patients and peripheral blood monoculear cells (PBMCs) from both patients and healthy controls. IL-10 production was accompanied by a decrease in tumour necrosis factor (TNF)-α production by synovial cells. Separation studies showed that the target cells were mainly monocytes. Accordingly, we observed that MTBHSP70 delayed maturation of murine bone marrow-derived dendritic cells. Our results suggest that MTBHSP may act on antigen-presenting cells (APCs) to modulate the cytokine response in arthritis and support an anti-inflammatory role for this protein, suggesting that it may be of therapeutic use in the modulation of arthritis.
High levels of type 2 cytokine-producing cells in chronic fatigue syndrome
Authors: SKOWERA A , CLEARE A , BLAIR D , BEVIS L , WESSELY S C , PEAKMAN M
Published: January 2004

The aetiology of chronic fatigue syndrome (CFS) is not known. However, it has been suggested that CFS may be associated with underlying immune activation resulting in a Th2-type response. We measured intracellular production of interferon (IFN)-γ and interleukin (IL)-2; type 1 cytokines), IL-4 (type 2) and IL-10 (regulatory) by both polyclonally stimulated and non-stimulated CD4 and CD8 lymphocytes from patients with CFS and control subjects by flow cytometry. After polyclonal activation we found evidence of a significant bias towards Th2- and Tc2-type immune responses in CFS compared to controls. In contrast, levels of IFN-γ, IL-2 and IL-10-producing cells were similar in both study groups. Non-stimulated cultures revealed significantly higher levels of T cells producing IFN-γ or IL-4 in CFS patients. Concluding, we show evidence for an effector memory cell bias towards type 2 responsiveness in patients with CFS, as well as ongoing type 0 immune activation in unstimulated cultures of peripheral blood cells.
Immune responses to glutamic acid decarboxylase and insulin in patients with gestational diabetes
Authors: FÜCHTENBUSCH M , BONIFACIO E , LAMPASONA V , KNOPFF A , ZIEGLER A-G
Published: January 2004

Pregnancy is a natural state of immunoprotection and tolerance. We studied subjects with gestational diabetes (GDM) to evaluate the influence of pregnancy on the humoral immune response to the autoantigen GAD and to injected insulin. Antibodies against glutamic acid decarboxylase (GADA) subclasses and epitope reactivity were determined in 34 GADA-positive pregnant patients with GDM, in 20 GADA-positive relatives of people with TID and in 25 GADA-positive patients with newly diagnosed TID. Partum levels of insulin antibodies (IA), IgG1- and IgG4-IA were measured in 131 women with GDM treated with human insulin from the time of diabetes diagnosis (including 22 with GADA) and were compared to 19 patients with TID after 3 months of insulin treatment. GADA titre and subclasses were similar among all groups. GADA in GDM patients bound fewer epitopes than GADA in relatives of patients with TID (all epitopes being present in 23%versus 65%, P < 0·01). In particular, antibodies to the minor GADA epitopes GAD6596–249, GAD651–100 and GAD67 were less frequent in patients with GDM compared to relatives (P < 0·01). Antibodies to insulin (IA) were found in 17% of patients with GDM. They were more frequent in GDM patients with GADA compared to GADA-negative patients (41%versus 12%, P < 0·005). IgG1 was the dominant insulin antibody subclass response in both patients with GDM and TID but levels of IgG1-IA and IgG4-IA were significantly lower in patients with GDM compared to patients with TID (P < 0·004). Antibody responses in women with gestational diabetes appear to be dampened and restricted, but without change in subclass usage.
Involvement of interleukin 18 in Crohn's disease: evidence fromin vitroanalysis of human gut inflammatory cells and from experimental colitis models
Authors: MAERTEN P , SHEN C , COLPAERT S , LIU Z , BULLENS D A M , VAN ASSCHE G , PENNINCKX F , GEBOES K , VANHAM G , RUTGEERTS P , CEUPPENS J L
Published: January 2004

An imbalance of immunoregulatory factors and/or cells contributes to uncontrolled mucosal T cell activation and inflammation in Crohn's disease (CD). Bioactive interleukin (IL)-18 has been shown to be produced by macrophages in CD lesions. We report here that T cells freshly isolated from inflamed tissue of CD patients (and not T cells from control intestinal tissue) were responsive to IL-18. In the presence of IL-18, these T cells produced more interferon (IFN)-γ and less IL-10. To analyse further the role of IL-18 in this disease, an acute and a chronic model of murine colitis were used. IL-18 mRNA was significantly enhanced in trinitrobenzene sulphonic acid (TNBS) induced colitis, and treatment with IL-18 binding protein (IL-18BPa), which neutralizes IL-18 bioactivity, significantly reduced the severity of colitis. However, IL-18BPa did not affect the course of chronic colitis in CD45RBhighCD4+ T cell reconstituted SCID mice. Production of IFN-γ in lamina propria mononuclear cell cultures from IL-18BPa-treated SCID mice was decreased, but at the same time fewer lamina propria CD4+ T cells harvested from IL-18BPa-treated mice compared to non-treated mice were in apoptosis. We conclude that IL-18 clearly has a modulatory role in the inflammatory cascade of CD and experimental colitis by affecting IFN-γ and IL-10 production, and apoptosis. In view of the divergent effects of IL-18 neutralization in the two different murine colitis models, it is unlikely that IL-18 is at the top of this cascade.
Interleukin-15 production by monocyte-derived dendritic cells and T cell proliferation in HIV-infected patients with discordant response to highly active antiretroviral therapy
Authors: D'ETTORRE G , FORCINA G , ANDREOTTI M , SARMATI L , PALMISANO L , ANDREONI M , VELLA S , MASTROIANNI C M , VULLO V
Published: January 2004

A discordant response to highly active antiretroviral therapy (HAART) occurs when CD4 T cell counts are stable or increased over time despite persistently detectable HIV-RNA levels. In order to identify immunological factors affecting discordant treatment responses, a total of 27 HIV-infected patients were studied: (a) 10 naive patients (mean CD4+ = 101·5 cells/µl; mean HIV-RNA = 4·8 log10 copies/ml); (b) seven responder patients (mean CD4+ = 908·9 cells/µl); and (c) 10 discordant patients (mean CD4+ = 396·1 cells/µl; mean HIV-RNA = 5·4 log10 copies/ml). Five healthy blood donors were included as HIV-seronegative controls. The following parameters were evaluated: interleukin (IL)-15 production by monocyte-derived dendritic cells (MDDC) after stimulation with lypopolysaccaride (LPS) and Candida albicans; recall and HIV-1-specific antigen lymphocyte proliferation (LP). Increased levels of IL-15 production by MDDC after stimulation with LPS and C. albicans were found both in discordant patients and responder patients. Conversely, a strong reduction of IL-15 levels was observed in naive patients. Discordant patients developed positive LP responses to C. albicans and HIV-1 p24. LP in response to C. albicans and HIV-1 p24 was also positive in responder patients. Decreased LP response was found in naive patients. In conclusion, HIV-infected patients with discordant viro-immunological responses to HAART present increased levels of IL-15 production by MDDC and enhanced recall and HIV-1-specific antigen LP responses, suggesting an improvement in indices of immune function.
Paneth cell granule depletion in the human small intestine under infective and nutritional stress
Authors: KELLY P , FEAKINS R , DOMIZIO P , MURPHY J , BEVINS C , WILSON J , MCPHAIL G , POULSOM R , DHALIWAL W
Published: January 2004

Paneth cells are important contributors to the intestinal antimicrobial barrier through synthesis and release of antimicrobial peptides and proteins. Animal studies indicate that Paneth cell numbers, location and granule morphology are altered by infection and zinc status. We examined human tissue to determine whether Paneth cell numbers, distribution or granule morphology are altered in infective, inflammatory and nutritional disorders. Archival sections from infective disorders (giardiasis, cryptosporidiosis, HIV, helminth infection) were compared with active inflammatory conditions (coeliac, Crohn's and graft-versus-host diseases) and histologically normal tissues. A subset of tissues was studied by electron microscopy and TUNEL staining for apoptosis. Human defensin-5 (HD5) peptide and mRNA was analysed by immunohistochemistry, in situ hybridization and quantitative reverse transcription polymerase chain reaction. Sections from a tropical population cohort study were then analysed to determine the relationship of granule depletion to infection, nutritional status and plasma zinc concentration. In HIV-related cryptosporidiosis, but not other disorders, Paneth cells were reduced in number and markedly depleted of granules. Paneth cell granule depletion was associated with reduced HD5 immunoreactivity, but this was not due to apoptosis and there was no reduction in mRNA transcripts. In the tropical population studied, depletion of granules was associated with reduced body mass index, reduced plasma zinc levels and HIV infection. Paneth cell granules in human small intestine may be depleted in response to infective and nutritional stress. We postulate that this is one mechanism through which zinc status influences host susceptibility to intestinal infection.
Toll-like receptor (TLR) 2 and 4 mutations in periodontal disease
Authors: FOLWACZNY M , GLAS J , TÖRÖK H-P , LIMBERSKY O , FOLWACZNY C
Published: January 2004

Toll-like receptors (TLR) are signal molecules essential for the cellular response to bacterial cell wall components. Different functional effective polymorphisms for the TLR 4 gene (Asp299Gly; Thr399Ile) and for the TLR 2 gene (Arg677Trp, Arg753Gln) have recently been described that are associated with impaired lipopolysaccharide signal transduction. A total of 122 patients with chronic periodontal disease and 122 healthy unrelated controls were genotyped for the Asp299Gly and Thr399Ile polymorphism of the TLR 4 gene and the Arg677Trp and Arg753Gln mutation of the TLR 2 gene. The mutations were identified with polymerase chain reaction followed by restriction fragment length polymorphism (RFLP) analysis. The prevalence of the Asp299Gly and the Thr399Ile mutant allele was 4·1% (10/244) and 4·5% (11/244) among periodontitis patients. For the healthy controls the prevalence was 3·3% (8/244) for the Asp299Gly (P = 0·810) and 3·7% (9/244) for the Thr399Ile mutant allele (P = 0·819). The Arg753Gln mutant allele was found in 2·9% (7/244) of the periodontitis subjects as compared to 4·1% (10/244) in the control group (P = 0·622). The Arg677Trp mutant allele was not found in any of the study subjects. Unlike in ulcerative colitis there was not observed an association between chronic periodontitis and the various mutations of the TLR 2 and 4 gene.
Preventing mother‐to‐child HIV transmission in the new millennium: the challenge of breast feeding
Authors: Kuhn Louise , Stein Zena , Susser Mervyn
Published: January 2004

Short courses of antiretroviral drugs have greatly enhanced the prospect of reducing mother‐to‐child HIV transmission. Yet transmission by breast feeding clouds hopes for this seemingly simple intervention. We revisit mathematical models to assess the competing risks associated with feeding by breast vs. formula. These indicate that, in the less developed world where the HIV epidemic predominates, neither option,unmodified, offers a reasonable choice for HIV‐positive women. Where infant mortality rates are greater than about 40 per 1000 live births, if formula were made available to HIV‐infected women only, the excess number of deaths that would result from formula use would be approximately the same or greater than the number of HIV infections that might be prevented. Only at lower infant mortality rates, less than about 40 per 1000, is the risk greater on the breast.

There are thus no good grounds for the total avoidance of breast feeding under all conditions. Research to develop and test safer infant feeding alternatives is an urgent priority. On the one hand, ways to reduce HIV transmission while preserving breast feeding, as exclusive breast feeding could do, need to be fully tested. On the other hand, ways to reduce non‐HIV morbidity and mortality associated with formula feeding, as educational or sanitary interventions could do, equally need testing. With either approach, a necessary foundation for implementing all the core components of preventing mother‐to‐child HIV transmission is competent counselling for mothers. Innovative approaches are needed to mobilise and train effective counsellors among health care workers and, as appropriate, community members.
Effect of indoor environmental factors on development of atopic symptoms in children followed up to 4 years of age
Authors: Gustafsson Dan , Andersson Kjell
Published: January 2004

The increased prevalence of atopic diseases reported in many Western countries is thought to be caused by changes in living conditions. For a long time attention was focused on indoor environmental factors and early feeding patterns, but during recent years other factors have received more attention. An unselected, Swedish, population‐based cohort of 904 children were followed from the age of 3 months to 4 years. Questionnaires were sent to the mothers of the children when they were 3 months, 18 months and 4 years of age. A blood sample was taken from a subgroup of the children when they were 4 years old which was analysed for IgE specific antibodies to food and inhalant allergens. The prevalences of asthma, allergic eye‐nose reactions, eczema, and food reactions at 4 years of age and a positive blood test were analysed as outcome factors.

Features of housing and early feeding patterns were found to have limited effect on the development of allergies in the children. Presence of older siblings resulted in a decreased tendency to produce IgE antibodies. Early exposure to furry animals seemed to prevent the development of asthma. Children who were frequently infected up to 18 months of age showed an increased prevalence of allergic symptoms at 4 years of age. Children of mothers with a higher prevalence of complaints about indoor factors, or who had increased general symptoms or skin or mucous membrane symptoms ran a greater risk of developing various allergic symptoms. However, these children did not have higher levels of IgE antibodies. The reported allergic symptoms in the children may be due to non‐immunological reactions, although it is also possible that the mothers may have over‐reported such symptoms.
Genetic epidemiology: some special contributions of birth cohorts
Authors: Pembrey Marcus
Published: January 2004

Birth cohorts that collect detailed phenotypic and environmental information, particularly if multigenerational, have an important contribution to make as we seek to understand the genetic and environmental determinants of common disease. Provided such multigenerational population cohorts are unselected by disease, trait or exposure, they can also contribute important information that is needed for optimal statistical analysis in genetic epidemiology generally. One example of this added value is an assessment, at specified loci, of whether or not there is distortion of the expected Mendelian 50 : 50 transmission of alleles to study subjects (e.g. due to differential loss of embryos of one genotype). Another example is to test for heterosis, i.e. whether heterozygotes have a greater or lesser effect than either homozygote. Finally, phenome scans (a fixed format analysis of the associations between a genotype of interest and thousands of outcome variables from the cohort database) could be used as a screening tool to test whether certain classes of genetic variation have more impact than others on human health and development, and so inform genotyping strategies generally.
The Belgrade childhood diabetes study: prenatal and social associations for type 1 diabetes
Authors: Šipetić Sandra , Vlajinac Hristina , Kocev Nikola , Saji´ Silvija
Published: January 2004

The aim of this study was to investigate whether prenatal and social factors are associated with the development of type 1 diabetes. A case‐control study was conducted in Belgrade during the period 1994–97. A total of 105 children ≤ 16 years old with recently onset of diabetes and 210 control children, individually matched by age (± 1 year), sex and place of residence, were included in the study. In the analysis using multivariable logistic regression, the following factors were significantly related to type 1 diabetes: poor socio‐economic status (Odds ratio = 4.18, 95% confidence interval [2.01, 8.72]); higher education of father (1.53, [1.16, 2.03]); complications during pregnancy (3.39, [1.64, 7.00]); ultrasound scan during pregnancy (0.40, [0.20, 0.79]); gestational age > 41 weeks (11.11, [1.80, 68.52]); mother's consumption of foods containing nitrosamines during pregnancy (3.14, [1.68, 5.87]); and consumption of alcohol by father (4.54, [2.34, 8.79]).
Changes in mean airway pressure during HFOV influences cardiac output in neonates and infants
Authors: Gullberg N. , Winberg P. , Selldén H.
Published: January 2004

Background:  Changes in mean airway pressure affect cardiac output during conventional positive pressure ventilation. The effect of high‐frequency oscillation ventilation (HFOV) on cardiac output is less studied.

Methods:  A prospective study in a university hospital pediatric intensive care unit. Fourteen patients aged <1 year and weighing <10 kg who were on HFOV were included. All patients had been on HFOV for >12 h and were considered to be in a stable condition. In the study group (n = 9) the mean proximal airway pressure (Paw) was increased and decreased by +5 and −3 cmH2O, respectively, from baseline in each patient. Measurements were made at each level including baseline settings between each change. In a control group (n = 5) no changes in ventilatory parameters were made. Cardiac output was assessed with echocardiography and the Doppler technique at each level of Paw and at similar intervals in the control group.

Results:  Cardiac output changed significantly when Paw was changed in the study group (P = 0.02), with the greatest change at the highest Paw at −11% (range: −19 to −9) compared with baseline. We found no significant changes over time in the control group.

Conclusion:  This study shows that CO is affected by changes in mean airway pressure during HFOV in concordance with the known effects of mean airway pressure during conventional positive pressure ventilation. The mean changes are smaller than expected compared with earlier studies of conventional mechanical ventilation. Further studies are needed to better understand these relationships.
Improved folate status in children and adolescents during voluntary fortification of food with folate
Authors: Wiltshire EJ , Couper JJ
Published: January 2004

Objective:  To assess longitudinal changes in folate status in South Australian children and adolescents during fortification of food with folic acid.

Methods:  Sixty‐nine children and adolescents (age 12.8 ± 2.3 years), 47 with diabetes and 22 healthy controls, had their folate status assessed at the beginning of 1999 and again after a mean 1.1 ± 0.23 years. Intake of folate at baseline was assessed with a quantitative food frequency questionnaire.

Results:  Baseline red cell folate (mean ± standard deviation (SD)) was 756 ± 294.5 nmol/L and remained constant at follow up at 736 ± 299 nmol/L (P = 0.55) in the whole group. Serum folate increased from 24.4 ± 6.3 nmol/L to 27.2 ± 8.8 nmol/L (P = 0.002). Children with diabetes showed a significant increase in serum folate (from 26.3 ± 5.7−30.1 ± 7.9, P < 0.001) and stable red cell folate (835.8 ± 278.6 and 808.6 ± 296.7, P = 0.51) between baseline and the second samples, while controls showed stable serum (20.4 ± 5.7 and 21.1 ± 7.7, P = 0.7) and red cell folate (586.6 ± 255.9 and 579.8 ± 240.1, P = 0.92). A third sample collected in 17 subjects after a further 9 ± 1.3 months showed a further increase in serum and red cell folate. Mean folate intake at baseline was 301 ± 129 µg/day, below the mean recommended for prevention of neural tube defects.

Conclusions:  Voluntary fortification of food with folate is associated with improved folate status in South Australian children and adolescents, but may not be sufficient at current levels to provide maximal protection against neural tube defects at a population level.
Cephalosporin resistant urinary tract infections in young children
Authors: Mehr SS , Powell CVE , Curtis N
Published: January 2004

Objective:  To describe the antibiotic resistance pattern of bacteria causing urinary tract infection (UTI) in a cohort of Australian children under 6 years of age.

Methods:  Data were collected over a 12‐month period from children under 6 years of age with a provisional diagnosis of UTI made in the Emergency Department of Sunshine Hospital, Victoria.

Results:  During the study period 100 culture‐proven UTI were identified in 97 children. Three children had two episodes. Out of the 100 episodes, 39% were male, 56% were under 12 months of age at presentation and 61% were managed as outpatients. Clinical features were non‐specific in the majority of cases. Hydronephrosis and vesicoureteric reflux was detected in 5.5% and 28.6%, respectively, of children with their first investigated UTI. A single bacterial isolate was cultured from 97 urines and two from three samples. Escherichia coli (n = 90) and Proteus mirabilis (n = 5) were the most common isolates. In vitro resistance to ampicillin/amoxycillin was found in 52% of isolates, to trimethoprim in 14% and to cephalothin/cephalexin in 24%. This resistance rate to first generation cephalosporins is the highest reported to date in adult or paediatric UTI in Australia.

Conclusions:  Ampicillin/amoxycillin or cephalothin/cephalexin may not be the optimal choice of antibiotic for the empiric treatment of UTI in this and possibly other paediatric populations.
Cerebral sinus venous thrombosis in children
Authors: Barnes C , Newall F , Furmedge J , Mackay M , Monagle P
Published: January 2004

Objective:  Cerebral sinus venous thrombosis (cerebral SVT) is rare in children. Information on clinical characteristics, radiological findings and outcome is emerging.

Methods:  Cases of cerebral SVT diagnosed between 1995 and 2001 were identified by a computer‐assisted search using International Classification of Disease codes. Medical records were reviewed to collect information on clinical presentation, investigations, treatment and outcome.

Results:  Sixteen cases of cerebral SVT were identified. All cases presented in association with head and neck pathology. The majority of cases presented with symptoms of raised intracranial pressure and focal neurological signs. Magnetic resonance imaging identified all cases of cerebral SVT whilst CT scanning failed to demonstrate the diagnosis in two cases. Management with anticoagulation was associated with radiological resolution of the thrombosis and normal neurological outcome. Long‐term follow up demonstrated neurological deficits in greater than 40% of patients.

Conclusion:  Cerebral SVT in children is associated with significant residual neurological morbidity. Prospective studies to identify predictors of outcome and effective management interventions are required.
A comparison between optimal and actuarial health care costs of adolescents with diabetes
Authors: Cameron FJ , Widdison J , Boyce D , Gebert R
Published: January 2004

Objective:  To assess actuarial cost and cost of optimal standards of care for adolescents with type 1 diabetes in a tertiary, hospital‐based care setting. To also assess actuarial costs of diabetic adolescents in psychosocial crisis.

Methods:  Contact diaries were maintained over a 1‐year period (June 1999−June 2000). Contacts recorded included both structured and non‐structured clinical encounters with contact times recorded. In addition, optimal or ‘ideal’ hospital‐based support and contact times for adolescents were estimated and recorded in minutes per year. Three illustrative cases of adolescents in psychosocial crisis were also assessed in terms of actuarial health care professional contact times. Costs were then calculated according to Victorian hospital pay structures per professional for 1999−2000.

Results:  The mean and median actuarial costs of caring for patients aged between 10 and 19 years were $A1307 per year and $A515 per year, respectively. The cost of optimal care for an adolescent was estimated at $A2817 per year after the first year of diagnosis. The costs per year of the three adolescents in crisis ranged from $A10 137 per year to $A30 524 per year.

Conclusions:  Cost benefits may be seen in the short term by reducing the number of adolescents who end up in psychosocial crisis. Current actuarial costs of diabetic care for adolescents falls short of an optimal standard of care. Diabetic adolescents who fall into psychosocial crisis consume a disproportionate share of a limited clinical resource.
Constitutive dependence in finite‐element modelling of crack closure during fatigue
Authors: ANDERSSON H. , PERSSON C. , HANSSON T. , MELIN S. , JÄRVSTRÅT N.
Published: January 2004

The influence of choice of constitutive relation on the prediction of crack‐opening stress for fatigue cracks using the finite‐element method is investigated and compared with experimental results. Two different experimentally obtained stress–strain relations for IN718 at 550 °C were used for fitting material parameters to the linear kinematic and the Bodner–Partom viscoplastic constitutive models. In addition, one reference material description and one Bodner–Partom with parameters fitted to both types of experiment was used, i.e., in total six constitutive descriptions. Experimental values for crack‐opening stress were found by the potential drop method for the two load cases analyzed. Two different load cases, load control and displacement control, have been examined. It turns out that the correlation between experimental and analytical crack‐opening stress vary significantly with material description, opening criteria in the simulation and load case. The investigation shows that care must be taken when choosing material description and opening criteria for crack propagation simulations.
Prediction of ductile fracture using isotropic and kinematic hardening rules including void nucleation
Authors: RAGAB A. R.
Published: January 2004

A formulation combining kinematic translation and isotropic expansion for a yield surface based on Gurson–Tvergaard function is used to describe void growth. By adopting a criterion of internal necking of the ligaments between voids, fracture strains for tensile bars made of conventional alloys and powder metal compacts—with micromechanical parameters mostly identified from experiments—are predicted according to kinematic, isotropic and mixed hardening models. Fracture strains predicted by the kinematic‐hardening model are in closer agreement with experiments whereas those estimated according to isotropic‐hardening model are overestimated. The consideration of either step‐like or continuous void nucleation models indicates its great influence on fracture strains and emphasizes a further need to quantify the statistical parameters involved in these models.