Dose Of Globulin Research Articles

A Single Centerʼs Experience With Adherence to a Newly Implemented Risk-Stratified Immunosuppression Protocol in Renal Transplant Patients.

Background: Modern immunosuppression protocols for renal transplantation balance the risks of over-immunosuppression, namely infection and drug toxicity, against the risk of rejection. There is limited literature for the optimization of immunosuppression by risk-stratification according to patient risk factors for rejection in renal transplantation. The aim of this study is to evaluate the degree of adherence to a newly implemented risk-stratified protocol. Methods: This is a retrospective single center study of the immunosuppression orders ordered for adult solitary kidney transplants during the risk-stratified (RS) protocol period from 2012 to 2013. Risk-stratification was based on immunological risk (sensitization and age) with total rabbit antithymocyte globulin (ATG) dosing ranging from 1.5 to 6 mg/kg to target an absolute lymphocyte count of less than 100 cells/μL. Results: 53 patients underwent renal transplantation during the RS period. Patient survival was 100% with 98% graft survival. During the initial transplant encounter, 81% of patients received the appropriately risk-stratified dose of ATG with the most common reason for protocol deviation being patients stratified to the incorrect level of immunologic risk. Of the ATG deviations, 50% of patients were dosed below protocol due to infection concerns and 50% were dosed above protocol due to rejection concerns. More than half (56%) of the patients who received an off-protocol dose of ATG were transplanted within the first 3 months of the protocol change. At discharge, the majority of patients were sent home on the protocol doses of prednisone and mycophenolate mofetil (76.9% and 71.7%, respectively). Slightly more than half of the patients were discharged on a dose of tacrolimus equaling 0.05 mg/kg twice daily or greater (52.9%), but the majority of patients had the per protocol-driven tacrolimus goal trough levels at discharge (88.2%). At one month post-transplantation, less than one-third (28%) of patients had tacrolimus trough levels within the designated trough levels. Conclusions: Despite an initial learning curve in the transition period, the implementation of a risk stratified immunosuppression protocol was successful and should translate to decreased infectious complications and excellent outcomes. Outpatient dosing and monitoring of tacrolimus may require further optimization to reach goal levels.

Bilateral lung transplantation for bronchiolitis obliterans after allogeneic bone marrow transplantation: a case report and literature review

To explore the feasibility and efficiency of lung transplantation in the treatment of bronchiolitis obliterans (BO) after allogeneic bone marrow transplantation (allo-BMT). We reported one case of bilateral lung transplantation for BO after allo-BMT and reviewed the related literatures. A 23 year-old man diagnosed as BO after allo-BMT underwent a sequential bilateral lung transplantation through bilateral anterolateral thoracotomy without sternal division. The patient suffered from acute rejection on post-operation day (POD) 2, and cured by mechanical ventilation, large dose of methylprednisolone and gamma globulin. The patient was transferred out of the intensive care unit on POD 14 and discharged from the hospital on POD 43. Chest CT scans and pulmonary function tests showed good performance in 3 and 6 months follow-up period. BO is one of the late common non-infectious pulmonary complication after allo-BMT. For patients who have no response to medication, lung transplantation is the only efficient treatment choice so far, which can prolong survival and improve the quality of life. However, limited by small samples, optimal surgery time and appropriate care of postoperative complications still need accumulation of experience by multicenter and large samples studies.

A high antithymocyte globulin dose increases the risk of relapse after reduced intensity conditioning HSCT with unrelated donors

The study included 110 consecutive patients with hematological malignancies receiving fludarabine-based reduced intensity conditioning (RIC) and hematopoietic stem cell transplantation (HSCT) from matched unrelated donors. The median age was 55 yr (range 11-68) and all but 15 patients received peripheral blood stem cell grafts. Antithymocyte globulin (ATG) (Thymoglobulin, Genzyme) at a total dose of 6 mg/kg (n = 66) or 8 mg/kg (n = 44) was given to all patients according to protocol. The ATG dose did not affect time-to-neutrophil or platelet engraftment. The incidences of acute GVHD grades II-IV were 34% and 18% (p = 0.11) and of chronic GVHD were 40% and 26% (p = 0.46) in patients receiving 6 and 8 mg/kg of ATG, respectively. The five-yr relapse-free survival (RFS) was 61% and 36% (p = 0.14) in patients, given low and high ATG dose, respectively. In patients given low-dose ATG, the incidence of relapse was lower compared to those given high-dose ATG, 19% vs. 41% (p = 0.04). In multivariate analysis, age >50 yr (p < 0.001), absence of acute (p < 0.001) and chronic GVHD (p = 0.001) were correlated to relapse, and low-dose ATG was associated with improved RFS (p < 0.05). A high dose (8 mg/kg) of ATG in RIC HSCT with unrelated donors increased the risk for relapse and reduced the RFS.

Pharmacokinetic and pharmacodynamic studies of two different rabbit antithymocyte globulin dosing regimens: Results of a randomized trial

Rabbit antithymocyte globulin (rATG; Thymoglobulin®) is currently used to prevent acute rejection in kidney transplantation. The dose and regimen of rATG have not been optimized. Moreover, the impact of different treatment regimens on T-cell phenotype reconstitution remains unknown. We conducted a prospective randomized study of 17 renal transplant patients to determine the pharmacokinetics of total and active (bound to human cells) rATG and T-cell phenotype reconstitution after rATG administration. Patients received rATG at a total dose of 6mg/kg, administered either as 1.5mg/kg/day on days 0–3 (Group 1, n=8) or 3mg/kg on days 0 and 3 (Group 2, n=9). All patients received tacrolimus, mycophenolate mofetil and steroids. Blood samples were assayed for total rATG by enzyme linked immunosorbent assay and active rATG by flow cytometry. Maximum concentrations and terminal half-lives were similar between the two groups but at month 3 Group 1 had significantly lower values for total rATG (concentration was 6.2±1.1μg/mL versus 10.2±2.9μg/mL in Group 2, p=0.027) and total rATG dose-normalized AUC (374±83dayg/mL versus 508±149dayg/mL in Group 2, p=0.046). Time to sub-therapeutic levels (<1μg/mL) of active rATG was significantly shorter in Group 1 (18.75±6.9days versus 20±7.5days in Group 2, p<0.001). rATG induced significant depletion followed by slow reconstitution of CD3+, CD4+ and CD8+ cells, with no marked differences between groups. B-cell count was unaffected, whereas CD3−CD56+ NK-cell depletion was observed in both groups. rATG induced a significant decrease in the proportion of naïve CD4+ T-cells, which plateaued after month 1 in Group 1 and after month 6 in Group 2. The proportion of central memory CD4+ T-cells increased to a similar extent in both groups (Group 1: 38±18% at baseline, 74±23% at one year, p=0.009; Group 2: 32±14% at baseline, 65±14% at one year, p=0.001). In conclusion, our results suggest that the dosing regimen for rATG induction influences pharmacokinetic parameters without affecting the quality of immune reconstitution.

A New Rat Model of Orthotopic Hemi-Abdominal Wall Allotransplantation

Introduction: Abdominal wall, the second mostly performed allotransplanted composite tissue, is less studied and lacking appropriate animal models. Its clinical necessities were emphasized in multiple case series to reconstruct large abdominal defects. The technical success is shadowed by problematic immunological and functional outcomes. We aim to establish a reproducible and cost-effective model to study the various treatment regimens, immune profile, and natural history of this specific allotransplant. Methods: Full thickness hemi-abdominal wall flap including the peritoneum is procured from Brown Norway (BN) rats and transplanted to an orthotopic defect on Lewis rats. Five groups were studied:Group 1: Lewis to Lewis syngeneicGroup 2: BN to Lewis controlGroup 3: BN to Lewis with 30 days CyclosporineGroup 4: BN to Lewis with 30 days Cyclosporine plus 4 doses of recipient adipose-derived stem cells (ADSC) intravenouslyGroup 5: BN to Lewis with 30 days Cyclosporine plus 4 doses of recipient ADSC subcutaneouslyGroup 3 to 5 also received one dose of anti-lymphocyte globulin on the day prior to surgery. Vascular imaging and cross sectional vessel biopsy were performed at the time of surgery and on day 60 along with full thickness abdominal wall biopsy. Immune cell profiling with flow cytometry at different time points was studied in all groups. Rejection is defined when de-epithelialization is first observed. Results: The rat abdominal model has near 100% surgical success rate. Syngeneic group showed no rejection. Control group consistently showed rejection on postoperative day 7. However, with cyclosporine treatment, rejection is delayed to day 50. ADSC plus cyclosporine currently showed even longer rejection-free period. No observable difference is yet seen between subcutaneous and intravenous ADSC groups. Interim cytometry results at time of rejection in control group indicated that Th1 cells mediate the rejection of abdominal wall transplant, whereas Th2 cells or IL-10-producing T cells down-regulate the rejection progression. Conclusion: We first developed a reproducible abdominal wall allotransplantation model in rats. Through this new model, we studied different immune modulation regimens, natural history, and immune profile of the allograft.Figure: [HAW]

Follow-up study on the clinical characteristics and treatment effect of the different types of Guillain-Barré syndrome in children

To study the clinical characteristics and effects of immunoglobulin treatment in children with the different types of Guillain-Barré syndrome (GBS). Data of 108 patients hospitalized for GBS were retrospectively analyzed; 75 cases in this group were given acute high dose of gamma globulin (IVIG) 400 mg/(kg·d) intravenously for 5 d. Clinical and electrophysiological data and information on treatment and recovery of the children were collected during the follow-up and were analyzed. According to the clinical and electrophysiologic findings, 32 patients manifested acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 34 had acute motor axonal neuropathy (AMAN), 3 had acute motor and sensory axonal neuropathy (AMSAN), 4 were inexcitable, 2 were unclassified. The clinical progress of the AMAN was faster than the AIDP group. Except for sensory nerve involvement, there was no significant difference in the clinical feature and severity. The mean time of the muscle strength began to recover was (5.59±3.63) days in the AIDP group and (7.21±4.68) days in the AMAN group after IVIG treatment. The time of the AIDP group was shorter than the AMAN group, but the difference was not statistically significant (t=-1.5702, P>0.05). The mean time of the muscle strength increased one grade was (8.88±4.39) days in the AIDP group and (12.67±8.35) days in the AMAN group. The difference was statistically significant (t=-2.3689, P<0.05). No patients in this group died. Follow-up data showed that the complete recovery time was not significantly different (t=0.2041, P>0.05). The clinical progress of the AMAN was faster than the AIDP group. Besides sensory nerve involvement, there was no significant difference in the clinical feature and severity. The AIDP group's clinical recovery was faster than AMAN's after the immunoglobulin treatment. The two groups were not significantly different in long-term prognosis.

Index of Suspicion in the Nursery

Twins are born at 37-5/7 weeks gestation to a 41-year-old G4P2 woman who had unremarkable serology results. The delivery is via cesarean section because of a nonreassuring fetal heart rate. Twin B appears to be acrocyanotic and initially requires positive-pressure ventilation for 30 seconds before being able to maintain her oxygen saturation on her own. Apgar scores are 7 and 8 at 1 and 5 minutes, respectively. She also appears to be “jittery,” and her screening glucose concentration is 24 mg/dL (1.3 mmol/L). She consumes 20 mL of infant formula and a 10% dextrose (D10) infusion is begun at a rate of 60 mL/kg per day. Three hours after birth, a follow-up glucose evaluation measures 30 mg/dL (1.7 mmol/L), prompting administration of a 4-mL/kg bolus of D10 over 20 minutes and increase of the maintenance infusion rate to 100 mL/kg per day. Six hours after birth, glucose measures 80 mg/dL (4.4 mmol/L), and the infusion rate is decreased to 60 mL/kg per day. She is transferred to a hospital that has a neonatal intensive care unit (NICU) for close monitoring. On transfer, the oxygen saturation dips into the upper 80s/lower 90s, and nasal cannula administration of oxygen is initiated. Furthermore, during transfer (8 to 9 hours after birth), the blood glucose value is 44 mg/dL (2.4 mmol/l), so the D10 infusion rate is increased back to 100 mL/kg per day. On arrival at the second hospital, her oxygen saturation is about 85% and glucose is 50 mg/dL (2.8 mmol/L). In the NICU, she receives noninvasive respiratory support as well as 15% dextrose (D15) at a rate of 70 mL/kg per day. Twin A remains stable and continues to receive routine newborn care in the newborn nursery of the first hospital. Two days after birth, twin B continues to have glucose …

Acute myocardial infarction in a child with myocardial bridge

Myocardial infarction (MI) is rare in children, and Kawasaki disease is now recognized as the main cause for MI. In this report, we present a child with MI caused by myocardial bridge (MB). A 7.5-year-old boy was admitted to Weifang People's Hospital on September 16, 2008 for heart disease. By electrocardiogram, coronary CT angiography, emission computed tomography, and other examinations, he was initially diagnosed as having (1) acute inferior myocardial infarction and extensive anterior myocardial infarction; (2) fulminant myocarditis; or (3) coronary myocardial bridge. He was treated with oxygen, thrombolysis, myocardial nutrition, vitamin C (4.0 g per time), dexamethasone (7.5 mg per time), a large dose of gamma globulin, and interferon. Myocardial enzymes, liver function, C-reactive protein, and troponin-I returned to normal at 21 days after treatment. At 29 days, electrocardiogram indicated that II, III, aVF, V4 - V6 leads had abnormal Q wave, and ST-T changed. The patient was discharged. Myocardial bridge may be one of the causes of MI in children.

70: Rabbit Antithymocyte Globulin Dosing and Complications in Heart Transplant Induction and Rejection

70: Rabbit Antithymocyte Globulin Dosing and Complications in Heart Transplant Induction and Rejection

Therapy of central pontine myelinolysis following living donor liver transplantation: Report of three cases

We analyzed the clinical manifestations and experiences of diagnosing and treating central pontine myelinolysis following living donor liver transplantation. The clinical data of three patients with central pontine myelinolysis following living donor liver transplantation from January 2005 to November 2007 were retrospectively analyzed at the West China Hospital, Sichuan University, China. The three patients developed hyponatremia prior to surgery. Case 1 suffered locked-in syndrome following surgery, and received a large dose of gamma globulin, and subsequently recovered. Case 2 was in a coma for three days, and received hyperbaric chamber treatment. This patient remained in a mild coma for six months following surgery. Case 3 developed consciousness disturbances, gradually went into a coma following surgery, and died due to pulmonary infection. Central pontine myelinolysis is a severe complication in patients following living donor liver transplantation. Large-dose gamma globulin treatment, as well as hyperbaric oxygen, might be effective therapeutic methods.

Genes Expressed by Both Mesangial Cells and Bone Marrow–Derived Cells Underlie Genetic Susceptibility to Crescentic Glomerulonephritis in the Rat

The Wistar-Kyoto (WKY) rat shows marked susceptibility to crescentic glomerulonephritis. In the model of nephrotoxic nephritis (NTN) that is induced by a small dose of nephrotoxic globulin, WKY rats developed crescents in 80 +/- 2% of glomeruli at day 10, whereas no crescents were seen in Lewis rats. This was associated with marked increase in monocyte chemoattractant protein-1 synthesis in WKY glomeruli. It was posited whether susceptibility depended on circulating cells or intrinsic renal cells. Bone marrow (BM) isografts from WKY to WKY or Lewis to Lewis did not affect susceptibility to NTN. When BM was transferred from WKY to Lewis rats, crescents developed in 35 +/- 9% of glomeruli 10 d after induction of NTN, indicating that susceptibility could be transferred by BM cells. However, crescents were also seen in WKY rats that were given Lewis marrow. For assessment of the contribution of intrinsic renal cells, kidneys from WKY or Lewis rats were transplanted into F1 animals. In NTN, the ratio of crescents in the transplanted kidney to the native kidney was significantly higher for WKY-to-F1 than for Lewis-to-F1 transplants, demonstrating that the kidney itself also influences susceptibility. Mesangial cell responses were then examined in the two strains. Mesangial cells that were derived from WKY rats synthesized significantly more monocyte chemoattractant protein-1 basally and after stimulation with heat-aggregated rabbit IgG or TNF-alpha. These results show that susceptibility to NTN in the WKY rat depends on both circulating and intrinsic renal cells and that there are genetic differences between the strains in mesangial responses to inflammatory stimuli.

A randomized prospective study on the use of 2 g-IVIG or 1 g-IVIG as therapy for Kawasaki disease

A single, 2 g/kg dose of immune globulin (IG), denoted 2 g-intravenous (IV)IG, has become a standard regimen for treating Kawasaki disease (KD) because of its highly preventive effect on coronary arterial lesions (CAL). However, IG is obtained from blood specimens, a drawback to many patients, and is also very expensive. This randomized prospective study reported here was carried out with the aim of developing a treatment regimen that would reduce the total dose of IG. The study tested two protocols (A: 2 g-IVIG; B: 1 g-IVIG) that included the strategy of administering additional IVIG to IVIG-resistant patients based on the criteria we described previously. In protocol A, an additional 2 g-IVIG was administered only once; in protocol B, the first additional IVIG was 1 g-IVIG and the second was 2 g-IVIG. One hundred and nine patients who were admitted before the seventh day of illness and had no CAL at the time of admission were enrolled in the study (protocol A: 54 patients; B: 55 patients). In the protocol A group, 7.4% (4/54) of the patients received 4 g/kg IG. In protocol B, 41.8% (23/55) were treated only with 1 g/kg IG, and 10.9% (6/55) received 4 g/kg IG. No significant differences were observed between the patients of the two subgroups receiving 4 g/kg IG in each protocol group. Discriminate analysis also suggested that 52.4% of the patients in the protocol A group could be treated only with 1 g/kg IG. On the other hand, no significant difference was observed in the incidence of aneurysms between patients in the protocol A group (1/54) and those in the protocol B group (4/55). Our protocol based on 1 g-IVIG, including additional IVIG, was assessed to be an effective treatment and to provide a considerably useful means to reduce the total dose of IG.

Persistent Fetal Hemoglobin in Maternal Circulation Complicating the Diagnosis of Fetomaternal Hemorrhage

Transplacental hemorrhage can be life threatening to a fetus and has important maternal treatment implications. In contrast, hereditary persistence of fetal hemoglobin is a condition that has little consequence. The Kleihauer-Betke test, which is routinely used to document transplacental hemorrhage, will be positive in either case. We report two cases in which maternal persistence of fetal hemoglobin was unknown and led to the erroneous diagnosis of fetomaternal hemorrhage. These cases highlight both the limitations of the Kleihauer-Betke test and the role of flow cytometry in diagnosing fetomaternal hemorrhage. The use of flow cytometry can clarify Kleihauer-Betke test results when there is known maternal persistence of fetal hemoglobin and can more precisely quantify a fetomaternal hemorrhage for accurate Rh immune globulin dosing.

CD8 + T cell dose affects development of acute graft-vs-host disease following reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation

Acute graft-vs-host disease (aGVHD) remains an important cause of morbidity after reduced-intensity conditioning (RIC) allogeneic transplantation (allo-SCT). It has been shown that antithymocyte globulin (ATG) dose infused during RIC is a major determinant for the likelihood of developing aGVHD. The ATG modulation on aGVHD is likely related to in vivo T-cell depletion. We therefore investigated the relationship between the cellular composition of the allograft and clinical outcome in 57 patients who received allogeneic peripheral blood stem cells from HLA-identical siblings following an ATG-based RIC. In a multivariate analysis, the CD8+ T cell dose infused was the only parameter associated with the risk of aGVHD (p=0.031; RR=1.96; 95% CI, 1.1-3.6). When looking at the extremes, patients experiencing grade III-IV aGVHD received a median of 143 x 10(6)/kg CD8+ T cells, while patients without aGVHD received a median of 96 x 10(6)/kg CD8+ T cells (p=0.021). None of the different cell subtypes contained in the allograft was associated with a significant probability of developing chronic GVHD. Patients with grade II aGVHD who received an intermediate dose of CD8+ T cells (median, 111 x 10(6)/kg) had a significantly better overall survival in comparison to patients with grade 0-I or grade III-IV aGVHD (p=0.009). In comparison to myeloablative allo-SCT, these results demonstrate that a cautious monitoring of the number of cells infused, at least in the context of ATG-based RIC, may represent an important predictive indicator of early transplant-related events and outcome after RIC allo-SCT.

CD8 T cell dose impacts acute graft-versus-host disease after reduced intensity conditioning (RIC) for allogeneic stem cell transplantation

6633 Background: We previously reported that the incidence of acute GVHD (aGVHD) was significantly associated with the antithymocyte globulin (ATG) dose (Sangstat*) infused during RIC using fludarabine, busulfan and ATG. The impact of ATG is likely related to a dose-dependent in vivo T cell depletion. Here, we investigated whether a correlation exists between graft composition and transplant-related events. Methods: 71 consecutive pts from a single center receiving HLA-identical RIC allogeneic transplantation, were analyzed. Median age was 50 y. (18–60), diagnosis: 34 myeloid malignancies (48%) and 37 lymphoid malignancies (52%). 51 pts (72%) were high risk. 38 pts (53%) received a low ATG dose (2.5 mg/Kg), while 33 received the highest dose (7.5 or 10 mg/Kg). 40 pts (56%) received PBSC and 31 (44%) received BM. All pts received CsA alone for GVHD prophylaxis. Results: 42 pts had aGVHD [13 grade I (18%), 12 grade II (17%) and 17 grade III-IV (24%)]. Chronic GVHD (cGVHD) occurred in 36 [8 limited (11%) and 28 extensive (39%)] out of 55 evaluable pts. Univariate analysis showed that stem cell source, ATG dose, CD4+, CD8+, CD19+ and CD56+ cells infused, significantly influenced the risk of aGVHD. In multivariate analysis, CD8+ T cell dose (>69x10e6/Kg) was the only parameter significantly associated with the risk of aGVHD (P=0.0002; RR=3.5; 95%CI, 1.8–6.7). The impact of CD8+ cell dose on aGVHD could be also confirmed if restricting the analysis to PBSC recipients (P=0.02). In contrast, in multivariate analysis, the risk of cGVHD was not statistically associated with lymphoid subsets, but was associated with grade II-IV aGVHD (RR=2.5; 95%CI, 1.2–5.0) and stem cell source (PBSC; RR=2.35; 95%CI, 1.1–5.0), suggesting that other cell subtypes (e.g. dendritic cells…) might contribute to long term imune reactions. With a median FU of 31 m (5–58), 37 pts are alive with OS being significantly higher in pts experiencing aGVHD and/or cGHVD as compared to pts without GVHD (P=0.004). Conclusions: These results suggest that graft manipulation may have a significant impact on the probability of a favorable outcome after RIC transplantation. No significant financial relationships to disclose.

Influence of antithymocyte globulin dose on outcome in cytomegalovirus-seropositive recipients of partially T cell-depleted stem cell grafts from matched-unrelated donors.

The adverse impact of positive-recipient Cytomegalovirus (CMV) serostatus on the outcome of matched-unrelated donor (MUD) grafts has been stressed. We evaluated whether CMV-seropositive MUD recipients transplanted after 1999 still showed inferior outcome compared with CMV-seronegative recipients. Two important changes in transplantation procedure were introduced in 1999: (1) reduction of antithymocyte globulin dose, (2) introduction of sequence-based typing of HLA-DRB1. Thirty-six patients received partial T cell-depleted grafts before 1999, and 44 after 1999. CMV-seropositive patients transplanted before 1999 showed a highly significant inferior outcome compared with seronegative recipients. In contrast, no difference in outcome was observed between the two groups of patients transplanted after 1999.

Fetal-Maternal Hemorrhage Detection in Ontario

The results from fetal-maternal hemorrhage (FMH) detection and quantitation external quality assessment surveys conducted in Ontario indicate that the rosette test had a sensitivity and specificity for an FMH of more than 10 mL of 1.0 and 0.75, respectively, compared with 0.96 and 0.92, respectively, for acid elution. With FMH quantitation, the percentage error of the mean from the target FMH was 20% or more in 7 of 8 surveys, and coefficients of variation ranged from 39.5% to 71.8%. Inadequate Rh o (D) immune globulin prophylaxis could have occurred in 19.4% of the challenges with an FMH of more than 10 mL. The rosette and acid elution techniques are both effective for the detection or exclusion of FMH, but acid elution lacks adequate accuracy and precision for reliable FMH quantitation. Furthermore, a strategy of prescribing an extra 1,500-IU Rh o (D) immune globulin dose, in addition to the dose required to treat the volume of fetal blood detected, is an effective strategy to overcome the limitations of FMH quantitation by acid elution. Hemolytic disease of the newborn (HDN) is the result of maternal antibodies causing destruction of antigen-positive erythrocytes in the fetus. The most serious form of HDN is caused by maternal alloantibodies directed against the D antigen of the Rh blood group system. In this scenario, Rh– mothers are alloimmunized during a previous pregnancy with an Rh+ fetus. HDN occurs in subsequent pregnancies involving an Rh+ fetus when maternal anti-D crosses the

Endogenous glucocorticoids modulate experimental anti-glomerular basement membrane glomerulonephritis.

The influence of endogenous glucocorticoids (GC) on glomerular injury was studied in a rat model of heterologous anti-glomerular basement membrane (GBM) glomerulonephritis (GN). Sprague-Dawley rats underwent adrenalectomy (ADX) or sham-operation 3 days prior to i.v. administration of both nephritogenic (100 microgram/g) and subnephritogenic (50 microgram/g) doses of sheep anti-rat GBM globulin. Administration of a subnephritogenic dose of anti-GBM globulin resulted in GN in adrenalectomized animals only. Similarly, ADX performed prior to administration of anti-GBM in the nephritogenic dose range resulted in exacerbation of GN compared with sham-operated animals (24 h protein excretion: 190.8 +/- 32.8 versus 42.5 +/- 2.6 mg/24 h; P < 0.005). In ADX animals receiving subnephritogenic doses of anti-GBM injury was manifested by abnormal proteinuria (62.7 +/- 5.8 mg/24 h), accumulation of neutrophils which peaked at 6 h (7.2 +/- 1.37 neutrophils per glomerular cross-section (neut/gcs)) and macrophage accumulation in glomeruli at 24 h (6.8 +/- 1.2 macrophages/gcs). Sham-adrenalectomized animals given the same dose of anti-GBM globulin developed minimal or no glomerular injury: urinary protein excretion (8.7 +/- 1.5 mg/24 h, P < 0.001); neutrophils (0.2 +/- 0.04 neutrophils/gcs, P < 0.001); macrophages (1.2 +/- 0.5 macrophages/gcs, P < 0.001). The increased cellular recruitment to glomeruli in adrenalectomized animals was associated with glomerular endothelial P-selectin expression. P-selectin expression was not detected in sham-operated rats after anti-GBM injection. Complement deposition in glomeruli was minimal in both groups. Physiologic GC replacement of ADX rats receiving subnephritogenic-dose anti-GBM reversed the observed susceptibility to GN development, with urinary protein excretion (7.8 +/- 1.12, P < 0.005) and no detectable P-selectin expression or leucocyte accumulation in glomeruli. These results suggest that endogenous GC modulate heterologous anti-GBM nephritis in rats and that this may be attributable, in part, to regulation of P-selectin expression.

Assessing the time of first onset of viremia, antigenemia, and dnaemia and the time to clearing during ganciclovir therapy fascilitates prediction of cytomegalovirus (CMV) disease vs. CMV syndrome in renal allograft recipients

The risk factors associated with CMV DNAemia are not well known after haploidentical stem cell transplantation (SCT).This study investigated the risk factors and prognosis for CMV DNAemia among CMV seromatched donors and recipients (D+/R+).A retrospective study of patients undergoing haploidentical stem cell transplantation (SCT) between January 2010 and January 2012 was conducted. Cox regression analysis was performed to identify the risk factors for CMV DNAemia. These possible factors included recipient/donor age, recipient/donor gender, gender disparity, recipient HBsAg serostatus, diagnosis, risk stratification, anti-thymocyte globulin (ATG) dose (6 mg/kg,10 mg/kg), early neutrophil engraftment (≤12 days, >12 days), absolute lymphocyte count on day 30 (ALC30) and the occurrence of acute GVHD before CMV DNAemia.The total number of patients was 248 with median age of 31 years (range, 14–56). The cumulative incidence of CMV DNAemia (146/248) was 59.5%. CMV DNAemia was first detected after a median of +35 days (range,12–82). Seventeen patients (17/146, 11.6%) developed CMV disease. Multivariate analysis identified HBsAg seropositivity (P = 0.002, hazard ratio (HR) = 1.833; 95%CI = 1.257–2.673) and the occurrence of acute GVHD before CMV DNAemia (P = 0.014; HR = 1.520; 95%CI = 1.088–2.124) as risk factors for CMV DNAemia. CMV DNAemia was associated with subsequent II-IV acute graft-versus-host disease (GVHD) (P = 0.014), III-IV aGVHD (P = 0.013) and chronic GVHD (P = 0.008). Totally, CMV DNAemia was found to be a poor prognostic factor in terms of non-relapse mortality (NRM) (P = 0.003, HR = 2.730; 95%CI = 1.406–5.197), and overall survival (OS) (P = 0.045, HR = 1.654; 95%CI = 1.012–2.701).Our data showed HBsAg seropositivity was associated with an increased risk of cytomegalovirus DNAemia. Detection of CMV DNAemia proved to be a poor prognostic factor for haploidentical patients.

The Pediatric Infectious Disease Journal® Newsletter

The Pediatric Infectious Disease Journal® Newsletter