The effects of gestational age on neonatal cholestasis: A retrospective cohort study.

BACKGROUND: Reference guidelines for neonatal conjugated hyperbilirubinemia (cholestasis) management use a uniform approach regardless of gestational age (GA). We hypothesize that the clinical pattern of neonatal cholestasis is tightly related to GA. The aim of this study was to describe the effects of GA on neonatal cholestasis. METHODS: A retrospective 4-year cohort study in a 70-bed neonatal care unit. Neonates with conjugated bilirubin≥34.2µmol/L (2 mg/dL) were identified. The incidence, clinical characteristics, etiology, treatment, and prognosis were compared between infants <32 and≥32 weeks GA. RESULTS: Overall incidence of cholestasis was 4% (125/3402). It was >5 times higher and the mean duration was >1.5 times longer in neonates <32 weeks GA (10% versus 1.8%, p <0.01 and 49 versus 31 days, p <0.01, respectively). The onset of cholestasis was later in neonates <32 weeks (22 versus 10 days of life, p <0.001). This later onset of cholestasis was associated with parenteral nutrition, whereas the earlier onset was associated with other causes. Treatment using fish oil lipids was more frequently administrated to infants <32 weeks GA, whereas Ursodeoxycholic acid was administrated more frequently in≥32 weeks GA. Cholestasis resolved during hospitalization in 73% of <32 versus 38% in≥32 weeks GA infants (p <0.01). CONCLUSIONS: The incidence, clinical presentation, etiology, treatment, and clinical evolution of neonatal cholestasis were all significantly affected by GA. Our results support the use of a GA-oriented approach for the management of neonatal cholestasis.

Oxygen and parenteral nutrition two main oxidants for extremely preterm infants: 'It all adds up'.

OBJECTIVES: To assess the effect of early exposure to O2 and parenteral nutrition (PN) on oxidative stress at 36 weeks post-menstrual age (PMA) and on bronchopulmonary dysplasia (BPD) in extremely preterm infants. STUDY DESIGN: A prospective observational study including 116 infants <29 weeks of gestation. Baseline clinical characteristics, FiO2 on day 7, duration of PN and clinical outcomes data were collected. In 39 infants, whole blood glutathione (GSH) and oxidized glutathione (GSSG) at 36 weeks PMA were measured and the redox potential was calculated using Nernst equation. Student's t-test, Chi-square, Spearman correlation, ANOVA, and logistic regression analyses were used as appropriate. P <  0.05 was considered significant. RESULTS: FiO2 ≥25% was associated with higher level of GSSG (0.29 ± 0.04 versus 0.18 ± 0.02 nmol/mg of protein), a more oxidized redox potential (-191 ± 2 versus -198 ± 2 mV) and more BPD (90% versus 45%). PN duration >14 days was also associated with higher level of GSSG (0.26 ± 0.03 versus 0.13 ± 0.02 nmol/mg of protein), a more oxidized redox potential (-193 ± 5 versus -203 ± 2 mV) and more BPD (89% versus 24%). In logistic regression model, each 1% increase in FiO2 and each day increase in PN duration resulted in an increase in the OR for BPD by 1.57 (1.09 -2.28) and 1.17 (1.03 -1.33) respectively. CONCLUSION: Early O2 supplement and PN have additive effects that were associated with prolonged oxidative stress and increased risk of BPD. Strategies targeting judicious use of O2 and decreasing the duration or developing a safer formulation of PN can be targeted to decrease BPD.

Analysis of the effects of iron and vitamin C co-supplementation on oxidative damage, antioxidant response and inflammation in THP-1 macrophages.

OBJECTIVES: The aims of the study were to test the susceptibility of THP-1 macrophages to develop oxidative stress and to deploy antioxidant defense mechanisms that insure the balance between the pro- and antioxidant molecules. DESIGN AND METHODS: Differentiated THP-1 were incubated in the presence or absence of iron-ascorbate (Fe/As) (100/1000µM) and the antioxidants Trolox, BHT, α-Tocopherol and NAC. RESULTS: Fe/As promoted the production of lipid peroxidation as reflected by the formation of malondialdehyde and H(2)O(2) along with reduced PUFA levels and elevated glutathione disulfide/total glutathione ratio, a reliable index of cellular redox status. THP-1 macrophages developed an increase in cytoplasmic SOD activity due in part to high cytoplasmic SOD1. On the other hand, a decline was noted in mRNA and protein of extra-cellular SOD3, as well as the activity of GSH-peroxidase, GSH-transferase and ATOX-1 expression. CONCLUSIONS: Macrophages activated under conditions of oxidative stress do not adequately deploy a powerful endogenous antioxidant response, a situation that can lead to an enhanced inflammatory response.

Long-term outcome after allo-SCT: close follow-up on a large cohort treated with myeloablative regimens.

We analyzed the late outcomes of 429 long-term survivors post allogeneic hematopoietic SCT (allo-HSCT) who received transplant in our center between 1981 and 2002, and were free of their primary disease for > or =2 years after allo-HSCT. Late recurrent primary malignancy was found in 58 (13.5%) patients and was the primary cause of late death. A total of 37 (8.6%) patients died of non-relapse causes at a median of 5.5 years (range, 2-15.6 years) post allo-HSCT. The major non-relapse causes of death were chronic GVHD (cGVHD), secondary malignancy and infection. The probabilities of OS and EFS were 85% (95% cumulative incidence (CI) (81-89%)) and 79% (95% CI (74-83%)) at 10 years, respectively. Long-term allo-HSCT survivors were evaluated for late complications (median follow-up, 8.6 years (range, 2.3-22.8 years)). cGVHD was diagnosed in 196 (53.1%) survivors. The endocrine and metabolic complications were hypogonadism in 134 (36.3%) patients, osteopenia/osteoporosis in 90 (24.4%), dyslipidemia in 33 (8.9%), hypothyroidism in 28 (7.6%) and diabetes in 28 (7.6%). Hypertension was diagnosed in 79 (21.4%), renal impairment in 70 (19.0%), depression in 40 (10.8%) and sexual dysfunction in 33 (8.9%) survivors. We conclude that in patients who receive allo-HSCT as treatment for hematological malignancy and who are free of their original disease 2 years post transplant, mortality is low and the probability of durable remission is high. Lifelong surveillance is recommended.

Predictors of outcome following myeloablative allo-SCT for therapy-related myelodysplastic syndrome and AML.

Administration of alkylating agents (Alk), topoisomerase II inhibitors (Topo II) and radiotherapy (RT) can result in therapy-related myelodysplastic syndrome or acute myelogenous leukaemia (t-MDS/t-AML), the optimal treatment for which is allo-SCT. A retrospective review was performed of 24 patients who underwent related- or unrelated-donor SCT for t-MDS/t-AML at our institution. Eight patients remain alive and in continuous remission (median follow-up 54 months (range, 12-161)) with estimated 5-year EFS being 30% (95% confidence intervals 16-58%). Corresponding actuarial risks of relapse and non-relapse mortality (NRM) are 39% (19-60%) and 30% (13-50%), respectively. EFS was 40% in Alk/RT-related t-MDS/t-AML and 11% in Topo II-related t-MDS/t-AML (P=0.05), with an increased risk of relapse in the latter (56 vs 29%, respectively (P=0.05)). In multivariate analysis, development of acute GVHD (P=0.009) and Topo II-related t-MDS/t-AML (P=0.018) were associated with inferior EFS. Patients with acute GVHD had an increased risk of NRM (P=0.03) whereas risk of relapse was higher for patients of advanced age (P=0.046) and for patients who underwent bone marrow (vs blood) SCT (P=0.032). Allo-SCT can result in long-term survival for individuals with t-MDS/t-AML although outcome in Topo II-related t-MDS/t-AML patients remains suboptimal.

Allogeneic SCT for relapsed composite and transformed lymphoma using related and unrelated donors: long-term results.

Outcome is poor with conventional therapy for relapsed transformed non-Hodgkin's lymphoma (NHL). Autologous SCT has been successfully employed; however the impact of allogeneic SCT has not been well defined. We therefore studied 40 consecutive patients who received allogeneic SCT for relapsed composite and transformed NHL (25 transformed, 8 composite (same site) and 7 discordant (different sites)) with related (n=25) and unrelated donors (n=15) to evaluate long-term outcome. Conditioning was myeloablative in the majority (39 of 40). Of 40 patients, 11 survive with median follow-up of 25 months. Death occurred in similar proportions due to relapsed NHL (n=14) or treatment-related complications (transplant-related mortality, TRM; n=15). The cumulative incidence of TRM was 36% at 3 years and disease relapse was 42% at 5 years. Probability of 2- and 5-year event-free survival is 36 and 23% with overall survival 39 and 23%. Performance of SCT within 1 year of NHL diagnosis predicted improved outcome. Relapse and TRM remain significant problems in this setting, indicating the need for strategies whereby patients at high risk of transformation should be selected for early SCT, ideally before their actual transformation.

Positive impact of selective outpatient management of high-risk acute myelogenous leukemia on the incidence of septicemia.

BACKGROUND: Curative intent chemotherapy for acute myelogenous leukemia (AML) leads to prolonged severe neutropenia, during which patients are highly susceptible to infection. Traditionally these high-risk patients were treated as inpatients. Our center recently implemented a selective ambulatory management policy for AML patients undergoing chemotherapy. MATERIALS AND METHODS: A retrospective analysis was conducted to assess the occurrence of septicemia in AML patients treated over a 5 years period with curative intent chemotherapy. This review encompasses a change in policy from primarily inpatient care to selective outpatient management coupled with prophylactic antibiotic therapy. RESULTS: A total of 294 patients, receiving 623 cycles of chemotherapy were identified. A significant decrease in septicemia was observed from the inpatient to outpatient cohort (22% to 13% P < 0.05), which correlated with the shift towards outpatient treatment of consolidation cycles. A shift from Gram-negative to Gram-positive organisms as the cause of septicemia was also detected in the outpatient cohort, likely due to the introduction of ciprofloxacin prophylaxis. No significant emerging resistance and no septicemia-related mortality were noted in the outpatient cohort. CONCLUSION: The observed decrease in the incidence of septicemia in the ambulatory cohort adds supportive evidence to the feasibility of selective outpatient management of AML patients with respect to infectious complications.

Placental oxidative stress in a rat model of preeclampsia.

The onset of preeclampsia is associated with increased maternal insult that could affect placental function. By increasing sodium intake (0.9% or 1.8% NaCl in drinking water) during the last week of gestation in the rat, we developed an animal model that shows many characteristics of preeclampsia such as increased blood pressure, decreased circulatory volume and diminished activity of the renin-angiotensin-aldosterone system. The aim of the present study was to determine in this model whether maternal perturbations in pregnancy lead to placental oxidative stress. Sprague-Dawley pregnant rats receiving salted-water were compared to not-supplemented pregnant rats. Markers of oxidative stress, ensuing cell death, and changes in the production of vasoactive substances (prostanoids: thromboxane, TxB(2); and prostacyclin, PGF(1alpha)) and the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha) were measured in the placenta. In tissue from pregnant rats on 1.8% NaCl supplement, 8-iso-PGF(2alpha) levels, TxB(2)/6-keto-PGF(1alpha) ratios, total TNF-alpha RNA expression, as well as the apoptotic index (Bax/Bcl-2 ratio) and endothelial nitric oxide synthase protein expression increase while total glutathione content decreases. These findings demonstrate that maternal insult during gestation induced an imbalance in the oxidative environment in the placenta favouring oxidation. This was accompanied by an increased synthesis of vasoconstrictive substances and TNF-alpha by the placenta as well as the increased rate of placental cell apoptosis.

Primary therapy for adults with T-cell lymphoblastic lymphoma with hematopoietic stem-cell transplantation results in favorable outcomes.

BACKGROUND: Controversy exists regarding the role of high-dose therapy followed by stem-cell transplant (SCT) in the treatment of T-cell lymphoblastic lymphoma (T-LBL). We conducted an intention-to-treat analysis of the strategy of SCT as definitive treatment of T-LBL. PATIENTS AND METHODS: From July 1987 to March 2005, 34 adults with T-LBL were diagnosed and treated in British Columbia. Treatment, before planned SCT, consisted of a non-Hodgkin's lymphoma (NHL)/acute lymphoblastic leukemia hybrid chemotherapy protocol (28 patients) or a standard NHL chemotherapy regimen (six patients). RESULTS: Median follow-up of the 23 surviving patients is 51 months (range 13-142 months). Twenty-nine proceeded to SCT (four allogeneic, 25 autologous). For all 34 patients, 4-year overall survival (OS) and event-free survival (EFS) are 72% and 68%, respectively. For patients proceeding to SCT, the 4-year OS and EFS are 79% and 73%, respectively. All patients who received allografts are alive without disease at 38-141 months since diagnosis. For patients who received autografts, the 4-year EFS is 69%. Bone marrow involvement was a significant prognostic factor predicting for a worse survival (P = 0.02). CONCLUSION: A treatment strategy for adults with chemosensitive T-LBL that includes planned consolidation with SCT in first response produces favorable long-term outcome.

Exaggerated vasomotor response to ANG II in rats with fetal programming of hypertension associated with exposure to a low-protein diet during gestation.

The renin-angiotensin system plays a key role in the initiation and maintenance of elevated blood pressure associated with altered intrauterine milieu. The current studies were undertaken to verify whether vascular response to ANG II is increased in adult offspring of low-protein fed dams (LP) compared with control (CTRL) and if so, to examine underlying mechanism(s). ANG II-induced contraction of carotid rings was increased in LP (E(max), the maximum asymptote of the curve, relative to maximal response to KCl 80 mM: 230 +/- 3% LP vs. 201 +/- 2% CTRL, P < 0.05). In both groups, contraction to ANG II was mediated solely by AT1R. Responses to thromboxane A2 analog U-46619 and to KCl 80 mM under step increases in tension were similar between groups. Endothelium depletion enhanced contraction to ANG II in both groups, more so in LP. Blockade of endothelin formation had no effect on response to ANG II, and ANG-(1-7) did not elicit vasomotor response in either group. Superoxide dismutase (SOD) analog Tempol normalized LP without modifying CTRL response to ANG II. Basal levels of superoxide (aortic segments, lucigenin-enhanced chemiluminescence and fluorescent dye hydroethidine) were higher in LP. ANG II further increased superoxide production in LP only, and this was inhibited by coincubation with diphenylene iodonium or apocynin (inhibitor of NADPH oxidase complex). AT1R expression in carotid arteries was increased in LP, whereas SOD expression was unchanged. In conclusion, vasoconstriction to ANG II is exaggerated in this model of developmental programming of hypertension, secondary to enhanced vascular production of superoxide anion by NADPH oxidase with concomitant increase of AT1R expression.

Shifting to outpatient management of acute myeloid leukemia: a prospective experience.

BACKGROUND: We assessed the feasibility of outpatient chemotherapy and supportive care in patients with acute myeloid leukemia (AML). PATIENTS AND METHODS: All patients receiving curative intent chemotherapy between 09/01 and 10/02 and meeting our criteria received supportive care post induction chemotherapy as well as their entire consolidation chemotherapy cycles as outpatients. Patients received antimicrobial prophylaxis; those developing episodes of fever and not meeting the criteria for admission were treated with outpatient intravenous antibiotics. RESULTS: Seventy-one cycles of induction chemotherapy were administered for newly diagnosed or relapsed AML. In 25 cycles the patient was discharged post chemotherapy prior to count recovery. Of these, 14 patients developed one or more febrile episodes as an outpatient and nine (36%) required readmission to hospital. Sixty-seven consolidation cycles were given on an outpatient basis. In 39 cycles there was one or more febrile episodes and in 14 (21%) admission was required. Infections were documented in four cases during induction and in 27 during consolidation. There were no treatment-related deaths. CONCLUSIONS: Outpatient management of AML is safe and feasible using the strategies outlined in this report.

Myeloablative allografting for chronic lymphocytic leukemia: evidence for a potent graft-versus-leukemia effect associated with graft-versus-host disease.

In all, 30 patients with CLL proceeded to myeloablative allogeneic BMT using related (n=20, 67%) or unrelated (n=10) donors, at the Princess Margaret Hospital (Toronto) (n=20) or the Leukemia/BMT Program of BC (Vancouver) (n=10), from 1989 to 2001. Median (range) interval from diagnosis to BMT was 4.8 (0.3-13) years, median number of prior therapies was three and median age 48 years. The preparative regimen included total body irradiation in 15 (50%). In all, 14 of 30 patients (47%) are alive, with median (range) follow up of 4.3 (2.4-10.5) years. All are in complete remission, two following therapy for post-BMT progression. Actuarial overall (OS) and event-free survival (EFS) at 5 years is 39% (OS 48% for related donor and 20% for unrelated donor BMT); cumulative incidence of nonrelapse mortality (NRM) and relapse is 47 and 19%, respectively. Both acute (RR=0.008, P=0.01) and chronic (RR=0.006, P=0.02) Graft-versus-host disease (GVHD) were associated with markedly decreased risk of relapse. Patients receiving grafts from unrelated donors had increased NRM (RR=3.6, P=0.02) and decreased OS (RR of death=3.4, P=0.002). Allogeneic BMT has resulted in long-term EFS in approximately 40% of patients with CLL. There is evidence for a strong graft-versus-leukemia effect associated with acute and chronic GVHD, resulting in near complete protection from relapse.

Characteristics and outcome of patients developing endocarditis following hematopoietic stem cell transplantation.

Endocarditis is an uncommon complication of hematopoietic stem cell transplantation (HSCT). A retrospective review of 1547 patients who underwent HSCT in Vancouver between January 1986 and December 2001 was performed. In all, 20 cases of endocarditis were identified (1.3% of all patients) with nine patients having received cryopreserved autologous stem cells, six stem cells from a histocompatible sibling and five patients stem cells from an unrelated donor. Five patients had endocarditis diagnosed while alive, a median of 6 months post-HSCT, by transthoracic (four patients) or transesophageal (one patient) echocardiography. The remaining 15 cases of endocarditis were only identified post mortem. The mitral valve was the most frequently involved (10 patients) followed by the aortic valve (six patients); multivalvular disease was noted in five patients. Of the 11 affected allogeneic HSCT patients, 10 had previously developed acute graft-versus-host disease (GVHD). Causative organisms were identified in 11 patients, while nine additional cases were felt to be thrombotic in origin. Of the 20 patients, 19 died with the sole survivor alive 10 years following an aortic valve replacement. Endocarditis is an uncommon complication of HSCT usually involving the cardiac valves on the left side of the heart and is associated with a high mortality rate.

Second malignancy following high-dose therapy and autologous stem cell transplantation: incidence and risk factor analysis.

To establish incidence and risk factors for development of second malignant neoplasms after high-dose chemo/radiotherapy (HDT) and autologous hematopoietic stem cell transplantation (AHSCT), the case files of 800 consecutive patients who underwent AHSCT at our institution between June 1982 and December 2000 were reviewed. In all, 26 patients developed 29 second malignancies (nine myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML), 16 solid tumors and four lymphoproliferative disorders (LPDs)) for a 15-year cumulative incidence of 11% (95% confidence interval (CI), 5-18%). These second tumors occurred at a median of 68 (range 1.5-177) months following AHSCT. The relative risk (RR) compared to the general population of developing a second malignancy following AHSCT was 3.3 (CI 2.2-4.7) P<0.001. The RR of developing MDS/AML, LPD and a solid tumor was 47.2 (CI 21.5-89.5) P<0.001, 8.1 (2.2-20.7) P=0.002 and 1.98 (1.1-3.2) P=0.009, respectively. In multivariate analysis, age >or=35 years at the time of AHSCT (P=0.001) and an interval from diagnosis to AHSCT >or=36 months (P=0.03) were associated with a greater risk of developing a second malignancy. Patients who have undergone HDT and AHSCT are at significant risk for developing a second malignancy and should receive indefinite follow-up.

Acute myelogenous leukemia complicated by acute necrotizing ulcerative gingivitis due to Aspergillus terreus.

Infections caused by Aspergillus terreus are rare but have been associated with a poor outcome in immunocompromised patients due to frequent resistance to conventional antifungal therapy. This report describes a case of a woman who developed acute necrotizing ulcerative gingivitis (ANUG) due to A. terreus during induction chemotherapy for acute myelogenous leukemia. She initially failed to respond to treatment with amphotericin B but the infection resolved following the introduction of oral itraconazole. Opportunistic infections caused by A. terreus are an emerging problem and can be associated with a high mortality rate. Early microbiological diagnosis is critical since resistance to amphotericin B is likely and itraconazole appears to be an effective treatment for this infection.

Fulminant tumour lysis syndrome in acute myelogenous leukaemia with inv(16)(p13;q22).

Tumour lysis syndrome (TLS) is caused by rapid breakdown of malignant cells resulting in electrolyte disturbances and acute renal failure. TLS has rarely been described in patients with acute myelogenous leukaemia (AML). Between November 1997 and July 2001, 114 consecutive adult AML patients aged <60 yr received induction chemotherapy consisting of cytosine arabinoside 1.5 g m(-2) q 12 h x 12 doses and daunorubicin 45 mg m(-2) d(-1) x 3 doses. During induction chemotherapy (CT), seven patients (6.1%, 95% CI 2.5-12.2) developed fulminant TLS, resulting in acute renal failure; five of these seven patients had inversion of chromosome 16 [inv(16)(p13;q22)], and one patient had a biological equivalent [t(16,16)(p13;q22)]. Four of the TLS patients underwent leukapheresis for a presenting white blood cell (WBC) count > 100 x 10(9) L(-1) prior to commencing chemotherapy, and six patients subsequently required haemodialysis for a median of 2 (range 1-8) wk. One TLS patient died of intracerebral hemorrhage on day 10 and another patient of multiorgan failure on day 17. Of the other five patients, all entered a complete remission (CR) and recovered normal renal function. Four patients remain in continuous CR [median follow-up 20 (range 12-25) months]. One patient relapsed at 12 months and again developed TLS on re-induction. In univariate analysis, TLS patients were more likely to have an elevated presentation and pre-chemotherapy WBC counts, elevated serum creatinine, and uric acid levels at presentation, as well as an inv(16). In multivariate analysis, only serum creatinine and inv(16) remained statistically significant (P < 0.001 for each). Patients with an inv(16) are a unique AML subgroup at high risk for fulminant TLS.

Changes in adolescents' conflict responses associated with consecutive presentation of hypothetical conflict situations.

The advantages of using hypothetical situations are one reason they have been widely used to examine adolescents' responses to conflict situations. One frequently used research protocol involves presenting several conflict scenarios to participants during a single session. However, in real-life situations multiple conflicts rarely occur within short periods of time, and the nature of this presentation may be associated with changes in adolescents' reports of conflict behaviors. Trend analyses of emotional, conflict goal, and conflict tactic responses from grade 8, 10, 12, and college students to consecutively presented conflict situations showed that responses were associated with presentation of the hypothetical situations. Findings revealed an increase in reports of assertive conflict behaviors and a decrease in reports of constructive conflict behaviors with successive situation presentation. Results from the current study suggest that researchers must consider trends in responses when examining findings from successive situation presentation methodologies because adolescent reports of conflict behavior may change as situation presentation proceeds.

Photoprotection of solutions of parenteral nutrition decreases the infused load as well as the urinary excretion of peroxides in premature infants.

Light exposure and multivitamins are contributing factors to the generation of peroxides in solutions of parenteral nutrition. This article verifies if peroxides infused with parenteral nutrition are of biological significance in neonates. The mechanisms responsible for the generation of peroxides in total parenteral nutrition solutions are reviewed. The consequences of infused peroxides on an index of oxidant stress and on levels of a central antioxidant are evaluated in an animal model. The effect of photoprotection of parenteral nutrition on a biological marker of redox imbalance is evaluated in the urine of premature infants. Parenteral multivitamins produce a drop in glutathione and an oxidant stress similar to peroxides in the lungs of newborn guinea pigs. Infused peroxides elicited an increased urinary peroxide excretion in infants receiving parenteral nutrition exposed to light. Photoprotection reduced levels of infused and excreted peroxides. The results suggest that peroxides infused with total parenteral nutrition are not fully quenched by premature infants.

Parenteral multivitamin supplementation induces both oxidant and antioxidant responses in the liver of newborn guinea pigs.

BACKGROUND: The multivitamin solution is a major component of photo-induced generation of peroxides in parenteral nutrition. The aim of this study was to determine whether the parenteral multivitamin preparation induces in the liver a peroxide-induced oxidant challenge or an antioxidant protection associated with the antiradical components of the solution. METHODS: Newborn guinea pigs were infused with dextrose supplemented with peroxides (250 micromol/L H2O2 or 350 micromol/L tert-butylhydroperoxide) or with a multivitamin preparation (MVP, 1% vol/vol). After 4 days, total glutathione and a free radical-sensitive eicosanoid marker (prostaglandin I2 [PGI2]/total prostaglandins) were measured in livers. RESULTS: There was a significant decrease in the PGI2/total prostaglandin ratio (mean +/- SEM) [dextrose: 0.068 +/- 0.007 vs. (dextrose + H2O2: 0.048 +/- 0.001, dextrose + TBH: 0.043 +/- 0.001)] and glutathione concentrations decreased [dextrose: 55 +/- 7 vs. (dextrose + H2O2: 37 +/- 7, dextrose + TBH: 18 +/- 7 nmol/mg protein)] after infusion of peroxides. Despite the peroxide load in the multivitamin solution, it did not alter the measured variables as prostanoid ratio remained at control concentrations (dextrose: 0.066 +/- 0.008 vs. dextrose + MVP: 0.065 +/- 0.006), as did glutathione levels (dextrose: 52 +/- 6 vs. dextrose + MVP: 45 +/- 7 nmol/mg prot). CONCLUSION: In the liver of guinea pig pups, infused peroxides cause oxidation of membrane-derived prostanoids. The decrease in glutathione in response to administration of peroxides suggests consumption rather than a response to a free radical attack. Despite the oxidant load associated with peroxides generated in MVP, the multivitamin preparation protected membranes as the prostanoid ratio, and glutathione levels remained at control levels.

Peer conflict avoidance: associations with loneliness, social anxiety, and social avoidance.

Failure to resolve peer conflict is associated with children's reports of loneliness, social anxiety, and social avoidance. Although these relationships are well established, researchers have not examined the association between the avoidance of peer conflict and various adjustment characteristics. The current study examined the association between avoidance of conflict and measures of loneliness, social anxiety, and social avoidance for 59 pupils in Grade 4 (31 boys and 28 girls) and 47 in Grade 8 (22 boys and 25 girls). Volunteers indicated that conflict avoidance based on autonomy, e.g., independence issues, and interpersonal issues, e.g., closeness and cohesion, was associated with scores on loneliness for boys and girls, respectively. Conflict avoidance for emotional and physical well-being and fear of punishment was associated with increased reports of loneliness and social anxiety for children in Grade 4.