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Background: Acute kidney injury (AKI) is a recognized comorbidity in pediatric diabetic ketoacidosis (DKA), although the exact etiology is unclear. The unique physiology of DKA makes dehydration assessments challenging, and these patients potentially receive excessive amounts of intravenous fluids (IVF). We hypothesized that dehydration is over-estimated in pediatric DKA, leading to over-administration of IVF and hyperchloremia that worsens AKI., Methods: Retrospective cohort of all DKA inpatients at a tertiary pediatric hospital from 2014 to 2019. A total of 145 children were included; reasons for exclusion were pre-existing kidney disease or incomplete medical records. AKI was determined by change in creatinine during admission, and comparison to a calculated baseline value. Linear regression multivariable analysis was used to identify factors associated with AKI. True dehydration was calculated from patients' change in weight, as previously validated. Fluid over-resuscitation was defined as total fluids given above the true dehydration., Results: A total of 19% of patients met KDIGO serum creatinine criteria for AKI on admission. Only 2% had AKI on hospital discharge. True dehydration and high serum urea levels were associated with high serum creatinine levels on admission (p = 0.042; p < 0.001, respectively). Fluid over-resuscitation and hyperchloremia were associated with delayed kidney recovery (p < 0.001). Severity of initial AKI was associated with cerebral edema (p = 0.018)., Conclusions: Dehydration was associated with initial AKI in children with DKA. Persistent AKI and delay to recovery was associated with hyperchloremia and over-resuscitation with IVF, potentially modifiable clinical variables for earlier AKI recovery and reduction in long-term morbidity. This highlights the need to re-address fluid protocols in pediatric DKA., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Introduction: Dialysis is potentially lifesaving in children with acute kidney injury (AKI) or chronic kidney disease (CKD), but availability is limited in low-income countries and lower-middle-income countries (LMICs)., Methods: In the present study, we perform a 4-year study of patients who received peritoneal dialysis (PD) or haemodialysis (HD) at the Paediatric Nephrology Unit of the University College Hospital Ibadan, Nigeria. Subgroup analysis was performed on patients with sepsis or malaria AKI who underwent HD or PD for predictors of in-hospital mortality., Results: A total of 167 children aged 7 days to 18 years, median 7 (interquartile range 3-12) years, (60.5% males) were studied. In total, 129 (77.2%) had AKI, while 38 had CKD. Regarding AKI, 83 children (64.3%) received HD only, 42 underwent PD only, while 4 underwent both HD and PD. Malaria AKI was treated with HD in 43 (51.8%) or PD in 8 (10.5%), while sepsis AKI was treated with HD in 20 (21.4%) or PD in 33 (78.6%). Mortality in AKI was 16.3% overall, 10.8% in children on HD only, and 26.2% in children on PD only. Patients with sepsis AKI had higher mortality compared to patients with malaria AKI (RR 7.96 [1.70-37.37]). Subgroup analysis showed that age, diagnosis, and dialysis modality were not independent risk factors for mortality. The aetiology of CKD was glomerulonephritis in 26 (68.4%): treatment was HD in 36 and PD in 2 with mortality being 26.3%., Conclusions: PD for AKI showed relatively good outcomes in a LMIC. However, funding and support for a formal dialysis program for the management of AKI and CKD are needed., (© 2022 S. Karger AG, Basel.)

Background & Aims: A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is a cell surface sheddase that regulates physiologic processes, including Notch signaling. ADAM10 is expressed in all intestinal epithelial cell types, but the requirement for ADAM10 signaling in crypt homeostasis is not well defined., Methods: We analyzed intestinal tissues from mice with constitutive (Vil-Cre;Adam10(f/f) mice) and conditional (Vil-CreER;Adam10(f/f) and Leucine-rich repeat-containing GPCR5 [Lgr5]-CreER;Adam10(f/f) mice) deletion of ADAM10. We performed cell lineage-tracing experiments in mice that expressed a gain-of-function allele of Notch in the intestine (Rosa26(NICD)), or mice with intestine-specific disruption of Notch (Rosa26(DN-MAML)), to examine the effects of ADAM10 deletion on cell fate specification and intestinal stem cell maintenance., Results: Loss of ADAM10 from developing and adult intestine caused lethality associated with altered intestinal morphology, reduced progenitor cell proliferation, and increased secretory cell differentiation. ADAM10 deletion led to the replacement of intestinal cell progenitors with 2 distinct, post-mitotic, secretory cell lineages: intermediate-like (Paneth/goblet) and enteroendocrine cells. Based on analysis of Rosa26(NICD) and Rosa26(DN-MAML) mice, we determined that ADAM10 controls these cell fate decisions by regulating Notch signaling. Cell lineage-tracing experiments showed that ADAM10 is required for survival of Lgr5(+) crypt-based columnar cells. Our findings indicate that Notch-activated stem cells have a competitive advantage for occupation of the stem cell niche., Conclusions: ADAM10 acts in a cell autonomous manner within the intestinal crypt compartment to regulate Notch signaling. This process is required for progenitor cell lineage specification and crypt-based columnar cell maintenance., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Practice variation is common for nephrotic syndrome (NS) treatment., Methods: A cross-sectional, web-based survey on NS treatment was administered to 58 Canadian pediatric nephrologists with the aim to document existing practice variation and compare practice with the recommendations of the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for NS., Results: Of the 58 nephrologists asked to participate in the survey, 40 (69 %) responded. Among these, 62 % prescribed initial daily glucocorticoid (GC) therapy for 6 weeks, 26 % for 4 weeks by 26 %, and 10 % prescribed 'other'. Alternate-day GC was continued for 6 weeks by 63 % of respondents and for >6 and <6 weeks by 32 and 6 %, respectively. For biopsy-confirmed minimal change disease, 65 and 46 % of respondents chose oral cyclophosphamide for frequently relapsing and steroid-dependent phenotypes, respectively; calcineurin inhibitors or mycophenolate were the second most popular choices. Kidney biopsy was 'always' performed by 16, 39, and 97 % of respondents for frequently relapsing, steroid-dependent, and steroid-resistant patients, respectively. Rituximab had been administered by 60 % of respondents; 22, 56, and 72 % reported that they would consider rituximab for frequently relapsing, steroid-dependent, and steroid-resistant patients, respectively. Most notable differences between practice and Guideline recommendations were first presentation GC duration, GC-sparing agent choices in frequently relapsing and steroid-dependent patients, and biopsy practices., Conclusions: There is substantial Canadian practice variation in NS treatment. Assessment of factors driving variation and strategies to implement Guideline recommendations are needed.

This review summarizes our current understanding of the role of cyclo-oxygenase inhibitors (COXI) in influencing the structural development as well as the function of the developing kidney. COXI administered either during pregnancy or after birth can influence kidney development including nephronogenesis, and can decrease renal perfusion and ultrafiltration potentially leading to acute kidney injury in the newborn period. To date, which COX isoform (COX-1 or COX-2) plays a more important role in during fetal development and influences kidney function early in life is not known, though evidence points to a predominant role for COX-2. Clinical implications of the use of COXI in pregnancy and in the newborn infant are also evaluated herein, with specific reference to the potential effects of COXI on nephronogenesis as well as newborn kidney function.

Children with severe cerebral palsy (CP) often have lower mineral intakes than healthy children. It is unknown if their lower nutrient intakes are adequate to meet their needs. The objective of this study was to examine the sodium, potassium, phosphate, and fluid status of primarily tube-fed nonambulatory children with severe CP. The design consisted of a cross-sectional exploratory study and a clinical trial of sodium supplementation. Nutritional status was determined among primarily tube-fed children (aged 2 to 17 years) with CP based on blood and urine samples, anthropometry, and 3-day food records. Mineral and fluid status was evaluated by a nephrologist blind to nutrient intakes. Twenty children supplied food records, blood samples, and anthropometric measurements, and 16 supplied urine samples. Six (37.5%) of those who provided urine samples were considered possibly dehydrated, as urine osmolality was >600 mmol·kg(-1). Six (60%) of the 10 children with satisfactory fluid status (low urine osmolality) were considered to have a possible dietary sodium deficiency based on a very low urine sodium concentration (<20 mmol·L(-1)). Those considered to have a possible dietary sodium deficiency had a significantly lower sodium intake (48% ± 15% Adequate Intake (AI)) compared with those considered sodium sufficient (73% ± 20% AI) (p = 0.031). One child was considered possibly phosphorus deficient, but none was assessed as likely potassium deficient. The conclusion was that sodium deficiencies were likely prevalent among the children. The findings from this small observational study suggest that sodium intakes for tube-fed children with CP should be maintained near the AI for their age. Hydration status of children receiving hypercaloric formulas should be monitored.

Background: Reports of long-term incidence trends of endemic diarrhea-associated hemolytic uremic syndrome (D+HUS) are few and inconclusive., Objective: To define and analyze the incidence and outcomes of D+HUS over a period of approximately 25 years in a highly endemic region of southern Alberta., Methods: Annual incidence rates of confirmed cases of D+HUS were compared between two 12-year periods (1980 to 1992 and 1994 to 2006). Differences in therapies used, and some short- and long-term complications observed were also compared between the two periods., Results: The absolute yearly number of D+HUS cases was highly variable. The comparison between the 1980 to 1992, and 1994 to 2006 periods demonstrated a modest 8.8% decrease in the total number of cases. The population-based average annual incidence rates were not significantly different between the two time periods (3.33 cases versus 2.58 cases per 100,000 population per year, respectively; P=0.30). Only supportive care measures were used in the latter period. A mortality rate of lower than 1% in the latter period was one of the lowest ever reported for a large cohort of D+HUS patients., Conclusion: The present long-term retrospective study of D+HUS in a highly endemic area documented a modest decrease in the absolute number of cases but no difference in the average annual incidence over an extended period of time.

Acute kidney injury (AKI) is becoming more prevalent among hospitalized children, its etiologies are shifting, and new treatment modalities are evolving; however, diarrhea-associated hemolytic uremic syndrome (D+HUS) remains the most common primary disease causing AKI in young children. Little has been published about acute renal replacement therapy (ARRT) and its challenges in this population. We describe our single center's experience managing 134 pediatric patients with D+HUS out of whom 58 (43%) required ARRT over the past 16 years. In our cohort, all but one patient were started on peritoneal dialysis (PD). Most patients, 47 (81%), received acute PD on a pediatric inpatient ward. The most common recorded complications in our cohort were peritoneal fluid leaks 13 (22%), peritonitis 11 (20%), and catheter malfunction 5 (9%). Nine patients (16%) needed surgical revision of their PD catheters. There were no bleeding events related to PD despite a mean platelets count of 40.9 (±23.5) × 10(3)/mm(3) and rare use of platelets infusions. Despite its methodological limitations, this paper adds to the limited body of evidence supporting the use of acute PD as the primary ARRT modality in children with D+HUS.

Introduction: Despite technical advances in spinal cord stimulation (SCS), there is a paucity of recent literature regarding SCS for phantom limb pain., Methods: Between January 2003 and May 2008, four patients at M.D. Anderson Cancer Center underwent SCS for intractable phantom limb pain. A retrospective chart review was performed to assess outcomes and complications. A PubMed search was performed to review previously published series regarding the efficacy of SCS for phantom limb pain., Results: Postoperatively, all patients subjectively reported excellent pain relief (>80%). Patients were all followed with the Brief Pain Inventory. Patients 1 to 3 each reported at wo-point decrease in their usual amount of pain using the numerical rating scale. Patient 4's numerical pain scale was unchanged. When using an 11-point scale to assess other symptomology along 10 dimensions, patients 1 to 3 demonstrated a decrease in their total symptom score by 13, 14, and 4 points, respectively. Patient 4 reported an increase by 5 points in his total symptom score. With regard to complications, patient 2 developed an allergic dermatitis to the generator requiring revision with a polyfluoroethylene (GorTex) pouch. Patient 3 developed a surgical site infection after an implantable pulse generator change. Patients 2 to 4 were very satisfied with their stimulator and would choose to undergo implantation again, with patient 1 having an equivocal response., Conclusions: For selected patients who have not obtained adequate relief with medical management, SCS for phantom limb pain can prove an effective intervention.

Information from four voluntary reports of hospital-acquired acute hyponatremia leading to the death of otherwise healthy children is highlighted. In this column, we present two cases and information from a recent ISMP Canada Safety Bulletin, as well as two cases reported to ISMP United States. Information is shared to enhance health care practitioners' awareness of the potential for acute hyponatremia and to provide an overview of some of the potential underlying factors.

NPHP is an autosomal recessive chronic tubulointerstitial nephropathy that progresses to ESRD. In the 2006 NAPRTCS report, NPHP was the primary diagnosis in 2.8% of all renal transplant patients. At our pediatric center, that covers a population in which the NPHP1 gene is prevalent, 24% of transplant recipients had a primary diagnosis of NPHP. Since no previous literature reports have documented kidney transplant outcomes in patients with NPHP, a review of the 2006 NAPRTCS database was performed. The results of this review illustrate that patients with NPHP as their underlying kidney disease have a significantly better overall graft survival when compared with all other patients registered in the NAPRTCS database. Sub-analysis demonstrated that this benefit is statistically significant only for LD kidney transplant recipients. CrCl was better in NPHP at all time points from transplant up to five-yr follow-up. Moreover, in NPHP LD transplant recipients the decline of CrCl over five yr was slower compared with non-NPHP LD transplant recipients. Rates of thrombosis, acute, and chronic rejection as well as causes of graft failure were similar in NPHP patients and all other patients. This review demonstrates that NPHP transplant recipients have excellent outcomes that are shown to be better compared with the general pediatric transplant population.

Objective: To test the null hypothesis that no difference in bracket failure characteristics is noted when use of a new ceramic bracket debonding instrument is compared with the use of conventional pliers., Materials and Methods: Thirty maxillary premolars were randomly assigned to one of two groups. In group 1, Clarity collapsible ceramic brackets (3M Unitek, Monrovia, Calif) were debonded with the use of conventional Utility/Weingart (3M Unitek, Monrovia, Calif) pliers. In group 2, Clarity brackets were debonded with a new Debonding Instrument (3M Unitek). For all teeth, the same bracket bonding system was used. Following debonding, teeth and brackets were examined under 10x magnification for assessment of bracket failure (fracture) and of residual adhesive on the enamel surface. Enamel surfaces were visualized with transillumination prior to bonding and after removal of the residual adhesive, so the effect of the debonding forces could be determined., Results: The results of Adhesive Remnant Index comparisons indicated that a statistically significant difference (chi2 = 8.73; P = .013) in bond failure patterns was apparent when the two groups were compared. Brackets debonded with the new instrument showed a greater tendency for the adhesive to be removed from the tooth during debonding., Conclusions: The hypothesis is rejected. Although the incidence of enamel damage following debonding was similar in the two groups, the use of the new Debonding Instrument decreased the incidence of bracket fracture.

This preliminary study explored the cultural socialization processes of 227 African American and European American parents of elementary schoolchildren. The Cultural Value Socialization Scales (K. M. Tyler, A. W. Boykin, C. M. Boelter, & M. L. Dillihunt, 2005) were used to garner parents' reports of their cultural value socialization activities at home. The scales contained written vignettes depicting persons involved in activity that reflected a specific cultural value. Ethnocultural values examined were communalism, verve, movement, and affect, and mainstream cultural values included individualism, competition, bureaucracy, and materialism. Regression analyses reveal that being an African American parent was predictive of competition and materialism scores. Race was not a significant predictor of the remaining cultural value socialization scores. Limitations to the study are discussed., (Copyright (c) 2008 APA, all rights reserved.)

Introduction: The effect of renal transplantation on areal bone mineral density (aBMD) in children has previously been studied. However, most previous reports did not include estimation of volumetric bone mineral density (vBMD) or analyze longitudinal data in these patients. In addition, updated reference standards for aBMD in children have recently been made available., Methods: This retrospective study describes the longitudinal effect of renal transplantation on aBMD and vBMD in a cohort of 40 pediatric kidney transplant recipients. Lumbar spine aBMD measurements were obtained using dual-energy X-ray absorptiometry prior to transplant and yearly thereafter. vBMD values and z-scores were estimated as described in the most recently published references., Results: A significant decrease in average aBMD and vBMD z-scores was observed within 1 year posttransplant, which did not recover during follow-up. The negative effect of transplantation on vBMD was blunted and vBMD z-scores were higher compared to aBMD. Linear mixed-effects model analysis demonstrated that lumbar spine aBMD and vBMD z-scores were inversely related to yearly prednisone dose (g/m2) but this effect was diminished as glomerular filtration rate was increased., Conclusions: Bone mineral density was negatively affected by renal transplantation in this cohort of pediatric patients. Estimation of vBMD appears to be appropriate for interpretation of the BMD changes occurring after renal transplant in children. The inverse relation between BMD z-scores and yearly prednisone dose suggests that ongoing posttransplant corticosteroid therapy may be responsible for the negative effect of transplantation on bone mineral density in this cohort.

Objective: To determine the influence of self-etching primer (SEP) application time on the shear bond strength of orthodontic brackets., Materials and Methods: Forty human molars were cleaned, mounted, and randomly divided into two groups. The same SEP, adhesive, and brackets were used in both groups. Twenty teeth were conditioned following the manufacturers' recommendations by rubbing the SEP on the enamel surface for 3 to 5 seconds. The remaining 20 teeth were conditioned using the same SEP, but the application time was increased to 15 seconds. The teeth were debonded within half an hour following initial bonding using a universal testing machine. After debonding, the amount of residual adhesive remaining on the tooth was determined. Student's t-test was used to compare the shear bond strength (SBS) of the two groups, and the chi2 test was used to compare the Adhesive Remnant Index (ARI) scores for the two adhesive systems., Results: The mean SBS of the brackets bonded to the teeth subjected to the SEP for 3 to 5 seconds was 8.0+/-4.6 MPa and was not significantly different (t=-0.69, P=.494) from the SBS of the brackets bonded using a 15-second SEP application time (x=8.9+/-3.4 MPa). The comparisons of the ARI scores between the two groups (chi2=2.16) indicated that bracket failure mode was not significantly different (P=.340) for both groups, and most failures were at the bracket-adhesive interface., Conclusion: The present findings indicate that increasing the SEP application from 3 to 5 seconds to 15 seconds does not result in a significant increase in SBS.

Hedgehog (Hh) signaling has long been recognized for its role in axial patterning, mesenchymal-epithelial inductive signaling, and growth regulation during fetal development. In many embryonic tissues, Hh functions as a proliferative stimulus. Sonic hedgehog and Indian hedgehog are both expressed by the urothelium of the fetal prostate anlage, where they regulate cell proliferation and differentiation and play a role in prostate ductal budding. Whereas Hh signaling in mouse prostate diminishes during adolescence and is maintained at a low level in the adult, robust Hh signaling is commonly found in the adult human prostate. The reason(s) for robust Hh signaling in the adult human prostate and the actions of Hh signaling on growth and differentiation in the adult are not well understood. However, increased Hh signaling has been associated with prostate cancer and has been shown to accelerate prostate cancer growth. These observations suggest that inappropriate reawakening of this developmental growth signal may play a pivotal role in prostate neoplasia. This review examines the role of Hh signaling during early prostate growth and in its corollary actions during prostate disease, including benign prostate hyperplasia and prostate cancer. The use of Hh inhibitors as a therapeutic modality for androgen-independent treatment of prostate disease is also discussed.

Polyuria is not considered an absolute indication for pre-transplant nephrectomy; however, it may complicate post-transplantation fluid management. Bilateral native-kidney laparoscopic nephrectomy was performed at our centre in two patients (four kidneys) 1 month after they had received a living related-donor renal transplant. The indication for nephrectomy was severe post-transplant polyuria secondary to the patient's underlying disease: juvenile nephronophthisis. Both patients had a persistent post-transplant daily urine output of 7-8 l/day and continued to have a variable serum creatinine level, dependent on intravenous hydration, more then 3 weeks after transplantation. Bilateral laparoscopic native-kidney nephrectomy in children has previously been reported. However, to the best of our knowledge, laparoscopic nephrectomy has not been described after kidney transplantation and certainly not in the immediate post-transplantation period. The procedure was well tolerated and did not affect renal graft function. In fact, following the procedure, serum creatinine levels stabilized, while daily fluid requirements decreased to 2.5-3.5 l/day in both patients. We concluded that bilateral native-kidney nephrectomy can be safely performed in paediatric renal transplant recipients in the immediate post-transplantation period. This new approach may allow preemptive transplantation and avoid the need for a transition period on dialysis in patients for whom pre-transplant nephrectomy is not absolutely indicated.

This study examined Ogbu's widely accepted thesis that African American students reject high academic achievement because they perceive its limited utility in a world where their upward mobility is constrained by racial discrimination. Boykin's psychosocial integrity model contends that Black students value high achievement but that discrepancies between their formative cultural experiences and those imposed in school lead them to reject the modes of achievement available in classrooms. Ninety Black children completed a measure of attitudes toward students who achieve via mainstream or African American cultural values. Participants rejected the mainstream achievers and embraced the African American cultural achievers. Moreover, they expected their teachers to embrace the mainstream achievers and reject those who achieved through high-verve behavior. Results suggest that Boykin's thesis is a needed refinement to Ogbu's ideas. They indicate that Black children may reject not high achievement but some of the mainstream cultural values and behaviors on which success in mainstream classrooms is made contingent.

The authors compared the performance of 78 African American 5th-grade students who studied a math-estimation task in one of two learning contexts. Learning contexts differed in the degree to which they afforded the expression of communalism. ANCOVA confirmed that posttest performance was best for students who studied in the high communal-learning context. The findings support A. W. Boykin's (1994) contention that the cultural context of learning can be a critical mediator of children's performance.

This study examined the influence of culture on students' perceptions of academic success. Students read scenarios depicting hypothetical classmates achieving success through the cultural themes of individualism, competition, communalism, or verve. Students reported their social endorsement for the hypothetical classmates. A 2x4 repeated measures analysis, examining the effects of cultural group and cultural theme on students' endorsement, revealed an interaction between the two variables. African American students were significantly more accepting of communal and vervistic high-achieving peers than European American students. European American students endorsed individualistic and competitive high achievers significantly more than African American students. These and other findings suggest that the value students attach to academic success should not be understood in the absence of cultural considerations., (Copyright (c) 2006 APA, all rights reserved.)

The authors of the present study have extended research by D. Marryshow that investigated African American students' attitudes toward 4 high achievers who differed in their approach to high achievement. D. Marryshow (1992) assessed students' social attitudes and perceptions of 4 high achievers with culturally distinct achievement orientations. In the present research, the authors assessed students' academic attitudes and perceptions of the same 4 high achievers. In addition, the present study includes Black children's predictions of their parents' and peers' attitudes toward these high achieving students. The results generally supported the authors' hypothesis that African American children would report a preference for students who achieve via attitudes and behaviors congruent with African American cultural values. The children also predicted that their parents and their Black peers would prefer these same African American culturally oriented high achievers. The findings suggest that Black children who prefer African American cultural modes of achievement may find themselves at odds with classroom demands geared toward learning in the mainstream cultural mode and thus may be at increased risk of academic failure.

Background: Graft survival in children who undergo kidney transplantation is lower than that in adults. The objective of the study was to review the experience of the first 22 years of operation of the regional pediatric kidney transplantation unit for Atlantic Canada, based at the IWK-Grace Health Centre, Halifax, and to use the results to improve graft survival., Methods: All cases of kidney transplantation performed at the centre from 1971 to 1992 were reviewed and the data compiled with the use of a predetermined database outline. Data for first transplants were analysed and compared with those in North American databases. Of the 40 graft failures, 19 (48%) occurred within the first 3 months after transplantation, a rate similar to that at other centres. The overall survival rates tended to be slightly lower than those of international databases. The introduction of cyclosporine A as an immunosuppressant, in 1985, did not provide the expected marked improvement in survival. Infection frequently accompanied acute rejection, and there was a delay in treatment of infections and rejection after discharge home. On the basis of these preliminary findings, several program changes were made: 1) a sequential immunosuppression protocol was implemented, 2) the intensity of the medical surveillance was increased for the first 3 months after transplantation, with aggressive treatment of infections and rejections, 3) a dedicated pediatric transplantation team was established as a subset of the adult team and 4) pediatric-specific selection criteria for cadaver donors were formulated. After these changes were implemented, data were collected and analysed up to June 30, 1997., Results: Graft survival rates at 1, 2 and 5 years improved dramatically. After the beginning of 1993, there were only 2 graft losses among 22 transplants. Only one of these occurred in the first 3 months, and it was due to recurrent disease. Twenty-four rejection episodes occurred (10 in the first 3 months after transplantation), but all were reversed easily with high-dose steroid therapy., Interpretation: Sequential immunosuppression with close medical surveillance and early aggressive treatment of infection and rejection contribute to a marked improvement in kidney graft survival in children.

The proportion of memory cells expressing the Pgp-1 surface marker, and subsets of T cells expressing L3T4 (CD4+ helper cells), Lyt-2 (CD8+ suppressor/cytotoxic cells), LFA-1 (lymphocyte function-associated antigen-1), and interleukin-2 receptors (IL-2R) on the cell surface in the spleen, regional lymph nodes (PLN), mesenteric LN (MLN), bronchial or mediastinal LN (BLN), Peyer's patches (PP), thymus, and bone marrow (BM) was studied in C57BL/6J mice of varying ages. Monoclonal antibodies (Mabs) IM7.8.1, FD4, GK1.5, 3.155, and FD441.8 were used to measure Pgp-1, IL-2R, L3T4 Lyt-2, and LFA-1 expressions, respectively. Optimal dose and kinetic studies were determined. The percentages of positive cells were determined by monoclonal antibody staining and flow cytometry or immunofluorescence microscopy. Using flow cytometric analysis, we found significant age-associated increases in the percentages of Pgp-1+ cells in the MLN as compared with a slight, but not significant, increase in the spleen. There were significant age-related increases in the percentages of Lyt-2+ cells in the spleen with no change in the MLN. The percentages of cells with the other phenotypic markers, L3T4, LFA-1, and IL-2R did not change with age in the spleen or MLN. Using immunofluorescence microscopy, the percentages of Thy-1.2+, Lyt-1+, and Lyt-2+ cells in different anatomical immune tissues did not change with age, except in the BLN and PP where there were significant age-related declines of the percentages of Thy-1.2+ and Lyt-2+ cells in the BLN, and of Lyt-1+ cells in the PP. These results indicate elevated levels of Pgp-1+ memory senescent cells in the MLN and these age-related shifts or changes in T lymphocyte subsets with age could contribute to the conserved immune responsiveness of senescent mucosal T lymphocytes.

The age-related tissue distribution of natural killer (NK) cell activity in murine muscular dystrophy was investigated. Lymphoid tissues including the spleen, thymus, mediastinal (or bronchial) lymph nodes (BLN), mesenteric lymph nodes (MLN), inguinal/popliteal lymph nodes (PLN1), and axillary/brachial lymph nodes (PLN2) were obtained from various aged normal (+/+) and dystrophic (dy2J/dy2J) C57BL/6J mice. Cell suspensions were incubated with 51Cr-labeled YAC-1 lymphoma target cells in a 4-hr 51Cr-release assay. The data indicated that dystrophic mice, at all ages studied, had elevated levels of NK activity in the spleen, BLN, MLN, PLN1, and PLN2 as compared with the normal age- and sex-matched control group. The NK activity in the thymocyte population from dystrophic mice at 2 weeks of age was found to be negligible, while at 8 weeks of age it was two-fold higher than that for the normal control group. In addition, dystrophic mice had an age-related decline in NK activity in all tissues after 10 weeks of age but the activity was still elevated at 40 weeks of age as compared with the normal control group. Target cell binding studies revealed that the number of conjugate-forming cells in thymocytes from 8-week-old dystrophic mice were found to be significantly higher than that found in normal mouse thymocytes using NK-sensitive YAC-1 tumor target cells. The number of cells bound per YAC-1 target cell ranged from 1 to 3 for dystrophic mouse thymocytes as compared with 1 to 2 for the normal control group. Thus, the data indicate an elevated NK activity in all lymphoid tissues studied from dystrophic mice of different ages. In addition, the thymus from dystrophic mice at 8 weeks of age contains an enhanced number of conjugate-forming NK cells and NK activity.

In the present study, we examined the changes that occur with age in anti-idiotype-blocked, hapten-augmentable PFC in the mucosal-associated lymph nodes (MLN and BLN) and spleen of various strains of mice. 2-month-old 129/J, AKR/J, and C57L/J mice had a high percentage of hapten-augmentable PFC in their spleen, MLN, and BLN; however, by 6-11 months these values had declined considerably in the spleen, while mucosal values remained high. In contrast, 2-month-old C57BL/6J, DBA/2J, and C3H/HeJ mice had a low percentage of hapten-augmentable PFC in their spleen, MLN, and BLN; but by 6-11 months these values had increased considerably in the spleen, while mucosal values remained low. CBA/J and SJL/J mice maintained high and low levels, respectively, of hapten-augmentable PFC in their spleens, MLN, and BLN over the age span. NZB/BinJ mice were found to be low producers in the spleen, but high in the MLN and BLN at 2 and 6 months of age. These data indicate that there are strain differences in the development of auto-anti-idiotypic antibody regulation with age.

Several lines of evidence support the notion that the mucosal-associated lymphoid system differs from the systemic. It is possible that the mucosal lymphoid system may also differ from the systemic system with regard to immune competence with age. Our findings in these studies indicate a lack of age-associated immune dysfunction in the mucosal-associated lymph nodes: that is, mesenteric and mediastinal lymph node PFC responses of old mice that revealed no decline in magnitude were found to be highly heterogeneous with regard to antibody affinity and revealed no appreciable anti-idiotype-blocked, hapten-augmentable plaque-forming cells. By contrast, the number of splenic and, as well, draining peripheral lymph node IgM, IgG, and IgA anti-TNP PFC responses to TNP-BGG was found to decrease with age with a preferential loss of high affinity plaque-forming cells. This decline in immune activity in the systemic tissues coincided with the increased appearance of anti-idiotype-blocked, hapten-augmentable plaque-forming cells. This differential effect of aging on immune responses in vivo of mucosal and systemic lymphoid tissues imply a site preference for an age-related decline in immune function, and a division of the immune system into regulatory compartments during the normal immune response to antigen in old mice. The present demonstration of a differential effect of aging on immune function in vivo raises an important issue with regard to age-related host defense mechanisms. For example, it would seem reasonable to predict that if immune function totally wanes with age, old individuals would be greatly susceptible to disease and infection. On the contrary, host defense mechanisms relevant to infection show minimal alterations in healthy aged individuals. Thus, we believe that mucosal immunity may play a very important role in host defenses in elderly individuals.

A rapid method for the analysis of antigen-specific human serum antibodies is described. After isoelectric focusing on thin agarose gels, serum proteins are transferred to nitrocellulose paper by capillary blotting. The kinetics of transfer indicated that ca. 90% of 125I-labelled isolated human immunoglobulins (IgG, IgA and IgM) are transferred to the nitrocellulose paper within 10 min. Probing of the nitrocellulose blot with 125I-labelled tetanus toxoid antigen followed by autoradiography reveals the total serum anti-tetanus toxoid antibody repertoire, including high molecular weight IgM. This procedure is rapid (results can be obtained in less than 12 h), sensitive and should prove very useful for detailed studies and analysis of antibody repertoires in body fluids and extracts