Outcome of fetuses with lower urinary tract obstruction and normal amniotic fluid volume in second trimester of pregnancy.

OBJECTIVE: Congenital lower urinary tract obstruction (LUTO) is a rare condition with high perinatal mortality and morbidity when associated with severe oligohydramnios or anhydramnios in the second trimester of pregnancy. Severe pulmonary hypoplasia and end-stage renal disease are the underlying causes of poor neonatal outcome in these cases. However, little is known about the subset of fetal LUTO that is associated with a normal volume of amniotic fluid at midgestation. The objective of the current study was to describe the natural history, underlying causes, survival and postnatal renal function outcomes in pregnancies with fetal LUTO and normal amniotic fluid volume during the second trimester of pregnancy. METHODS: This was a retrospective study of all pregnancies with fetal LUTO and normal amniotic fluid volume in the second trimester that received prenatal and postnatal care at our quaternary care institution between 2013 and 2017. Data on demographic characteristics, fetal interventions, perinatal survival, need for neonatal respiratory support, postnatal renal function and need for dialysis at the age of 1 and 24 months were analyzed. RESULTS: Of the 18 fetuses that met the study criteria, 17 (94.4%) survived the perinatal period. Eleven (61.1%) pregnancies developed oligohydramnios in the third trimester, six of which were eligible for and underwent fetal intervention with vesicoamniotic shunt placement, which was performed successfully in all six cases. Two (11.1%) neonates required respiratory support owing to pulmonary hypoplasia. At the age of 2 years, 14 children had follow-up information available, two (14.3%) of whom had normal renal function, eight (57.1%) had developed some degree of chronic kidney disease (Stage 1-4) and four (28.6%) had developed end-stage renal disease (ESRD), including two who had already manifested ESRD in the neonatal period. CONCLUSIONS: Most fetuses diagnosed prenatally with LUTO that is associated with a normal volume of amniotic fluid at midgestation will have a favorable outcome in terms of perinatal survival and few will need long-term respiratory support. However, these children are still at increased risk for chronic renal disease, ESRD and need for renal replacement therapy. Larger multicenter studies are needed to characterize the prenatal factors associated with postnatal renal function, and to investigate the role of fetal intervention in the group of fetuses that present with late-onset oligohydramnios and evidence of preserved fetal renal function. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Report on The Society for Fetal Urology panel discussion on the selection criteria and intervention for fetal bladder outlet obstruction.

INTRODUCTION: The Society for Fetal Urology panel section at the 2016 Fall Congress featured a multidisciplinary discussion on appropriate patient selection, the conservative versus surgical management, and postnatal renal outcome of fetuses with lower urinary tract obstruction (LUTO). SELECTION CRITERIA FOR INTERVENTION: Rodrigo Ruano shared his experience of prenatal intervention, presenting the outcome of 111 fetuses with severe LUTO treated with vesicoamniotic shunting (VAS) (n = 16), cystoscopy (n = 34) or no intervention (n = 61) in a non-randomized series. Multivariate analysis at the 6-month follow-up suggested a significantly higher probability of survival with fetal intervention versus no intervention. A clear trend for normal renal function was present in the fetal cystoscopy group, but not in the VAS group. In cases in which there was a postnatal diagnosis of posterior urethral valves (n = 57), fetal cystoscopy was effective in improving both the 6-month survival rate and renal function, while VAS was associated with an improvement in the 6-month survival rate. In an attempt to better define which fetuses would benefit from intervention, Michael Braun explained the proposed LUTO classification system that incorporates: (1) fetal urinary biomarkers of renal injury; (2) amniotic fluid levels as a surrogate for the severity of obstruction; and (3) imaging studies to identify signs of renal dysplastic or cystic changes. Intervention was not recommended in patients at low risk of either renal disease or pulmonary hypoplasia (Stage 1). Vesicoamniotic shunting was performed in patients at high risk of either progressive renal injury or pulmonary hypoplasia without evidence of severe pre-existing renal damage (Stage 2). For those patients, who at the time of evaluation had evidence of severe renal disease (Stage 3), fetal intervention was individualized and often based on bladder capacity and bladder refilling after vesicocentesis. He went on to present the nephrologic outcome of fetuses managed over the last 3 years utilizing the selection criteria. Craig Peters supported the concept of selective criteria and discussed the cautious viewpoint, namely: (1) the procedure may be unnecessary, as it is possible for patients to do well, in spite of severe prenatal obstruction; and (2) the risk of giving partial treatment by allowing the baby to survive to delivery with the daunting postnatal journey of renal and pulmonary insufficiency. CONCLUSION: Standardized patient selection utilizing a staging system is undoubtedly the way forward and will enable comparable long-term renal and bladder functional outcome studies.

Fetal lower urinary tract obstruction: proposal for standardized multidisciplinary prenatal management based on disease severity.

OBJECTIVE: To present a single center experience of a standardized prenatal multidisciplinary management protocol for fetal lower urinary tract obstruction (LUTO) and to propose a classification of fetal LUTO based on disease severity. METHODS: This was a retrospective cohort study of 25 consecutive fetal patients with prenatal diagnosis of primary LUTO. Fetal intervention was offered after evaluation by a multidisciplinary team. Analyses were conducted using Bayesian methodology to determine predictors of survival at 6 months postpartum. Odds ratios (ORs) with 95% credibility intervals are reported. RESULTS: Fifteen (60.0%) of the 25 patients referred for assessment survived to postnatal evaluation. Fetal vesicoamniotic shunt was placed in 14 (56.0%) patients with 12 survivors. Multivariable analysis suggested that fetal intervention (OR, 6.97 (0.88-70.16), Pr(OR > 1) = 96.7%), anhydramnios (OR, 0.12 (0.04-0.35), Pr(OR < 1) = 99.9%), favorable fetal urine analysis (OR, 3.98 (0.63-25.15), Pr(OR > 1) = 92.7%) and absence of renal cortical cysts (OR, 3.9 (0.66-24.2), Pr(OR > 1) = 93.3%) were predictors of survival. CONCLUSIONS: Fetal intervention and fetal renal function were independently associated with postnatal survival of fetuses with LUTO. A classification based on the severity of disease is proposed. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Urological fistulas after fetal cystoscopic laser ablation of posterior urethral valves: surgical technical aspects.

OBJECTIVE: To describe the surgical technical aspects associated with the development of urological fistulas after fetal antegrade cystoscopic laser fulguration of the posterior urethral valves (PUV). METHODS: The perioperative data for all fetal cystoscopies performed between January 2004 and August 2013 at three institutions in the USA, France and Brazil were reviewed, with particular emphasis on surgical technical aspects of the procedure and the complications encountered. RESULTS: A total of 40 fetal cystoscopies were performed at the three institutions. Laser fulguration of the PUV was performed in 23 of these cases, with a survival rate of 60.9% (14/23) and normal renal function in 85.7% (12/14) of these infants. Urological fistulas were diagnosed postnatally in four (10%) newborns. The presence of fistulas was associated with a higher gestational age at diagnosis of PUV (P < 0.01) and with the use of semi-curved rather than curved sheaths (P < 0.01), the use of a diode laser (P < 0.01) and the use of higher laser power and energy (P < 0.01 and P < 0.01, respectively), as well as with less operator experience (P < 0.01) and with absence of fetal anesthesia/immobilization (P = 0.02). CONCLUSION: Urological fistulas are a severe complication of fetal cystoscopic laser fulguration of PUV and are associated with type, energy and power settings of the laser and instrumentation. The use of appropriate technique and proper training of the operator are necessary to perform this fetal intervention safely.

Diversity in the preimmune immunoglobulin repertoire of SHR lines susceptible and resistant to end-organ injury.

We used next-generation sequencing to identify immunoglobulin heavy chain (IGH) genetic variation in two closely related hypertensive rat lines that differ in susceptibility to end-organ disease (SHR-A3 and SHR-B2). The two SHR lines differ extensively at the IGH locus from the rat reference genome sequence and from each other, creating 306 sequence unique IGH genes. Compared with IGH genes mapped in the rat reference genome sequence, 98 are null gene alleles (31 are null in both SHR lines, 45 are null in SHR-A3 only and 23 are null in SHR-B2 only). Of the 306 divergent gene sequences, 126 result in amino acid substitution and, among these, SHR-A3 and SHR-B2 differ from one another at the amino acid level in 96 segments. Twelve pseudogenes in the rat reference genome sequence had changes displacing the stop codon and creating probable functional genes in either or both SHR-A3 and SHR-B2. A further five alleles that encoded functional rat reference genome sequence genes or open reading frames were converted to pseudogenes in either or both SHR-A3 and SHR-B2. These studies reveal that the preimmune immunoglobulin repertoire is highly divergent among SHR lines differing in end-organ injury susceptibility and this may modify immune mechanisms in hypertensive renal injury.

Activation of the formyl peptide receptor by the HIV-derived peptide T-20 suppresses interleukin-12 p70 production by human monocytes.

It has been proposed that in the early stages of human immunodeficiency (HIV) infection, before the loss of CD4(+) T cells, inhibition of IL-12 production from host antigen-presenting cells plays a critical role in the suppression of T-helper cell type 1 responses. Activation of the G(i)-protein-coupled high-affinity N-formyl peptide receptor by f-met-leu-phe and HIV-derived peptide T-20-suppressed IL-12 p70 production from human monocytes in response to both T-cell-dependent and T-cell-independent stimulation are reported. Activation of the low-affinity N-formyl peptide receptor by the HIV-derived F-peptide suppressed IL-12 production more modestly. This suppression was pertussis toxin sensitive and was selective for IL-12; the production of IL-10, transforming growth factor-beta, and tumor necrosis factor-alpha was unaltered. The production of IL-12 p70 by dendritic cells was unaffected by these peptides despite functional expression of the high-affinity fMLP receptor. These findings provide a potential direct mechanism for HIV-mediated suppression of IL-12 production and suggest a broader role for G-protein-coupled receptors in the regulation of innate immune responses. (Blood. 2001;97:3531-3536)

Regulation of interleukin-12 production by G-protein-coupled receptors.

G-protein-coupled receptors have long been known to play a critical role in the recruitment and migration of leukocytes to areas of inflammation. This review will focus, however, on emerging data that G-protein-coupled receptors can modulate cytokine production by antigen-presenting cells including interleukin-12 and tumor necrosis factor-alpha and may therefore play a significant role in the regulation of innate and acquired immunity.

CD40-CD40L independent Ig gene hypermutation suggests a second B cell diversification pathway in humans.

Somatically mutated IgM(+)-only and IgM(+)IgD(+)CD27(+) B lymphocytes comprise approximately 25% of the human peripheral B cell pool. These cells phenotypically resemble class-switched B cells and have therefore been classified as postgerminal center memory B cells. X-linked hyper IgM patients have a genetic defect characterized by a mutation of the CD40L gene. These patients, who do not express a functional CD40 ligand, cannot switch Ig isotypes and do not form germinal centers and memory B cells. We report here that an IgM(+)IgD(+)CD27(+) B cell subset with somatically mutated Ig receptors is generated in these patients, implying that these cells expand and diversify their Ig receptors in the absence of classical cognate T-B collaboration. The presence of this sole subset in the absence of IgM(+)-only and switched CD27(+) memory B cells suggests that it belongs to a separate diversification pathway.

Salivary epidermal growth factor and intestinal adaptation in male and female mice.

Salivary epidermal growth factor (sEGF) levels are increased in male mice after small bowel resection (SBR) and may be important during intestinal adaptation. Since males have greater sEGF than females, the influence of sex on postresection adaptation was tested. Females had lower sEGF; however, sEGF substantially increased in both sexes after a massive (50%) SBR. Adaptive increases in DNA and protein content, villus height, and crypt depth, as well as crypt cell proliferation rates in the remnant ileum, were not different between males and females. Although significant postresection increases in sEGF were identified, EGF mRNA and protein did not change within the submandibular gland. Glandular kallikrein-13 and ileal EGF receptor expression were greater after SBR in female mice. Intestinal adaptation is equivalent in female and male mice after SBR. Despite lower sEGF, females demonstrated increased expression of a kallikrein responsible for sEGF precursor cleavage as well as amplified ileal EGF receptor expression. These results endorse an important differential response between sexes regarding sEGF mobilization and intestinal receptor availability during adaptation.

Selective suppression of IL-12 production by chemoattractants.

We investigated the ability of chemoattractants to affect IL-12 production by human monocytes and dendritic cells. We found that pretreatment of monocytes with macrophage chemoattractant proteins (MCP-1 to -4), or C5a, but not stromal-derived factor-1, macrophage inflammatory protein-1alpha, RANTES, or eotaxin, inhibited IL-12 p70 production in response to stimulation with Staphylococcus aureus, Cowan strain 1 (SAC), and IFN-gamma. The production of TNF-alpha and IL-10, however, was minimally affected by any of the chemoattractants. The degree of inhibition of IL-12 p70 production by MCP-1 to -4 was donor dependent and was affected by the autocrine inhibitory effects of IL-10. In contrast, C5a profoundly suppressed IL-12 production in an IL-10-independent fashion. Neither TGF-beta1 nor PGE2 was important for the suppression of IL-12 by any of the chemoattractants tested. The accumulation of mRNA for both IL-12 p35 and p40 genes was inhibited by chemokine pretreatment. Interestingly, MCP-1 to -4 and C5a did not suppress IL-12 production by monocyte-derived dendritic cells (DC) stimulated with CD40 ligand and IFN-gamma or by SAC and IFN-gamma, suggesting that these factors may act at the site of inflammation to suppress IL-12 and IFN-gamma production rather than in the lymph node to affect T cell priming. Despite the inability of C5a to inhibit IL-12 production by DCs, the receptor for C5a (CD88) was expressed by these cells, and recombinant C5a induced a Ca2+ flux. Taken together, these results define a range of chemoattractant molecules with the ability to suppress IL-12 production by human monocytes and have broad implications for the regulation of immune responses in vivo.

The perioperative role of the neurosurgical service coordinator.

At one institution, the development of a position of Neurosurgical Service Coordinator was implemented to expedite the neurosurgical procedures in the operating room. The position required a registered nurse experienced in the field of neurosurgical nursing, who could schedule surgical cases, train personnel, manage budgetary requests, and coordinate a department of 10 neurosurgeons performing 1,500 cases annually.

Differences between membranoproliferative glomerulonephritis types I and III in long-term response to an alternate-day prednisone regimen.

Membranoproliferative glomerulonephritis (MPGN) is classified as type I, II, or III based on ultrastructural alterations in the glomerular basement membrane. Whereas type II has long been recognized as clinically and pathologically unique, types I and III are often difficult to distinguish and have not been separated in most clinical studies. We compared the course and long-term outcome of patients with types I and III MPGN followed up at this institution since 1960. During this period, 21 patients with type I and 25 patients with type III were followed up for a minimum of 5 years. Patients with types I and III MPGN did not differ in age at apparent onset, age at diagnosis, or interval from apparent onset of symptoms to diagnosis (biopsy). They had similar initial serum C3 and serum albumin levels. Patients with type I had a significantly lower initial mean estimated glomerular filtration rate (GFR(est)) compared with those with type III (99.1 +/- 35.9 versus 131.6 +/- 36. 1 mL/min/1.73 m(2); P < 0.01). Type and duration of therapy, length of follow-up, and frequency of complications of therapy did not differ between groups. There was, however, a significant difference in duration of hypocomplementemia. After 1 year of an alternate-day prednisone regimen, 90% of the type I patients normalized their serum C3 levels compared with less than 50% of type III patients (P < 0.01). After 3 years of therapy, only 5% of type I patients were hypocomplementemic compared with 33% of type III patients (P < 0.02). In addition, disease relapse occurred in six type III patients (24%) compared with no type I patients. At last follow-up, type I patients had a slight improvement in mean GFR(est) (+6.3 +/- 48.4 mL/min/1.73 m(2)), whereas type III patients had a 25% decrease in mean GFR(est) (-34.8 +/- 47.6 mL/min/1.73 m(2); P < 0.01). Residual urinary abnormalities were significantly more frequent in patients with type III than type I MPGN. Hematuria persisted in 72% versus 38% (P < 0.05) and proteinuria in 28% versus 0% (P < 0.01) of those with types III and I, respectively. These results give clear evidence of significant differences in the clinical progression of the two types and their response to the alternate-day prednisone regimen. Whereas the outcome of patients with type I MPGN treated with alternate-day prednisone was generally good, similarly treated patients with type III experienced significant reductions in renal function, slower improvement in serum C3 levels, more persistent urinary abnormalities, and more frequent relapses.

Cholera toxin suppresses interleukin (IL)-12 production and IL-12 receptor beta1 and beta2 chain expression.

Cholera toxin (CT) is a potent mucosal vaccine adjuvant, which has been shown to induce T helper cell type 2 (Th2) responses in systemic and mucosal tissues. We report that CT inhibits the production of interleukin (IL)-12, a major Th2 counterregulatory cytokine. IL-12 p70 production by stimulated human monocytes was inhibited by CT in a dose-dependent manner. This suppression occurred at the level of gene transcription, was maximal at low concentrations of CT, and was dependent on the A subunit of the toxin, since purified CT B subunit had minimal effect. CT also inhibited the production of IL-12 p70 by monocyte-derived dendritic cells, as well as the production of tumor necrosis factor alpha, but not IL-10, IL-6, or transforming growth factor (TGF)-beta1, by stimulated monocytes. The effects of CT were not due to autocrine production of IL-10, TGF-beta1, or prostaglandin E2. CT inhibited the production of IFN-gamma by anti-CD3-stimulated human peripheral blood mononuclear cell, due in part to suppression of IL-12 production, but also to the inhibition of expression of the beta1 and beta2 chains of the IL-12 receptor on T cells. In vivo, mice given CT before systemic challenge with lipopolysaccharide had markedly reduced serum levels of IL-12 p40 and interferon gamma. These data demonstrate two novel mechanisms by which CT can inhibit Th1 immune responses, and help explain the ability of mucosally administered CT to enhance Th2-dependent immune responses.

Continuous venovenous hemodiafiltration in the treatment of acute hyperammonemia.

Acute hyperammonemia is an emergent cause of central nervous system dysfunction for which renal replacement therapy is advocated. We report the successful use of continuous venovenous hemodiafiltration in this metabolic emergency, and report the calculated ammonia clearances for both continuous venovenous hemofiltration and hemodiafiltration.

Nephrotic syndrome accompanying familial hemophagocytic syndrome.

PURPOSE: We describe the first reported case of familial hemophagocytic syndrome (FHS) with concurrent minimal change nephrotic syndrome (MCNS). PATIENTS AND METHODS: This is a case report of a 30-month-old girl who presented to Children's Memorial Hospital with pancytopenia and heavy proteinuria. RESULTS: This patient presented with anemia, neutropenia, thrombocytopenia, hypertriglyceridemia, and proteinuria. A brother died at 2 months of age with similar findings. A bone marrow biopsy demonstrated histiocyte proliferation with marked erythrophagocytosis, consistent with FHS. Treatment was begun with corticosteroids and VP-16. The patient developed worsening peripheral edema and hypoalbuminemia, with heavy proteinuria. After 1 month of therapy with persistence of heavy proteinuria, a renal biopsy was performed, the results of which were consistent with MCNS. CONCLUSION: This is the first reported case of FHS with coincident MCNS.

Further studies using X-ray fluorescence to sample lead contaminated carpeted surfaces.

The sampling of carpeted surfaces to test for lead contamination primarily focuses upon vacuum techniques. Vacuum sampling techniques, however, require time-consuming, expensive laboratory analysis of the dusts obtained and are unable to determine total lead load on the carpet. X-ray fluorescence (XRF) analysis is an on-site, inexpensive, non-destructive, quick technique for predicting metals levels in a variety of media, such as water, soil, filter paper and painted surfaces. A 1992 study of the feasibility of XRF to analyze for lead and soil loadings on carpeted surfaces indicated that XRF can detect lead at a low enough level to warrant further study. This paper expands this earlier study and developes lead and soil loading calibration curves for three different carpet types based upon XRF lead L-beta peak areas and XRF iron and barium K-alpha peak and background areas. Results indicate that variation in the data can be reduced through modifications of the XRF analysis technique, thus reducing the statistically determined detection level, and that carpet type does affect the calibration. Detection levels of approximately 70 mg/m(2) for lead and 5 g/m(2) for soil were obtained. Overall, good agreement was found between results of this study and the earlier one. XRF shows excellent potential for quantitative analysis of lead on carpeted surfaces.

The use of X-ray fluorescence to detect lead contamination of carpeted surfaces.

The recognition of the hazards to young children of low-level lead intoxication and the widespread distribution of lead in the urban environment have resulted in massive federal, state, and local lead awareness and abatement programs. Two of the most significant exposure routes of lead to young children are the soils and dusts found within the child's home. Most state and federal lead abatement programs deal with lead-based paint contamination but often do not address the issue of soft-surface contamination, such as that of carpets, furniture, and draperies. Carpets can be a reservoir of contaminated soils and dusts; currently, there exists no standard method to test carpeted surfaces for lead contamination.This paper describes a study that uses X-ray fluorescence (XRF) to test carpeted surfaces for lead contamination. XRF technology is the standard technology used in lead-based paint testing and is known to be an accurate technique to test for lead in soils. This study uses a controlled laboratory atmosphere to evaluate this technology; the objectives are to determine: (1) a lower limit of detection for the instrument; and (2) whether soil loading levels can be differentiated by XRF using trace elements also present in the soil. Results indicate that XRF can easily differentiate soil loading levels (g soil/m(2) carpet). The lower limit of detection of soil lead concentration on the carpet is a function of both soil lead concentration and soil loading; therefore, lead loading (mg Pb/m(2)) is a better indicator of detection limit than soil lead concentration. Lead loading detection levels from 108-258 mg Pb/m(2) were obtained, as compared to a level of 10 000 mg/m(2) (1 mg/cm(2)) for lead on painted surfaces as required by theLead-Based Paint Poisoning Prevention Act.XRF technology has the potential to be a fast, inexpensive screening technique for the evaluation of lead contamination on carpeted surfaces.

[Acute petroleum poisoning in infants in Gabon]. / Les intoxications aigues par le pétrole chez l'enfant au Gabon.

Acute intoxications with petroleum are frequent in children: we have seen 36 cases in a year in the General Hospital, Port-Gentil (Gabon), service of pediatrics. Pulmonary lesions are aggravated by vomitus; radiological signs appear after half an hour, interest the right side and are characterized by an interstitial syndrome. Evolution is always good with antibiotherapy. Prevention consists in health education.