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Background: Owing to structural-level, interpersonal-level, and individual-level barriers, Latino men have disproportionately high rates of physical inactivity and experience related chronic diseases. Despite these disparities, few physical activity (PA) interventions are culturally targeted for Latino men., Objective: This study reported the feasibility and acceptability of Hombres Saludables PA intervention for Latino men. We also reported the preliminary efficacy of the intervention on PA change and provided the results of the exploratory moderator and mediator analysis., Methods: We completed a 6-month, single-blind, pilot randomized controlled trial of Hombres Saludables with Latino men aged between 18 and 65 years. Men were randomized to either (1) a theory-driven, individually tailored, internet-based and SMS text message-based, Spanish-language PA intervention arm or (2) a nutrition and wellness attention contact control arm that was also delivered via the web and SMS text message. We assessed the primary study outcomes of feasibility using participant retention and acceptability using postintervention survey and open-ended interview questions. We measured the preliminary efficacy via change in minutes of moderate to vigorous PA per week using ActiGraph wGT3X-BT accelerometry (primary measure) and self-reported minutes per week using 7-day Physical Activity Recall. Participants completed the assessments at study enrollment and after 6 months., Results: The 38 participants were predominantly Dominican (n=8, 21%) or Guatemalan (n=5, 13%), and the mean age was 38.6 (SD 12.43) years. Retention rates were 91% (21/23) for the PA intervention arm and 100% (15/15) for the control arm. Overall, 95% (19/20) of the intervention arm participants reported that the Hombres study was somewhat to very helpful in getting them to be more physically active. Accelerometry results indicated that participants in the intervention group increased their PA from a median of 13 minutes per week at study enrollment to 34 minutes per week at 6 months, whereas the control group participants showed no increases. On the basis of self-reports, the intervention group was more likely to meet the US PA guidelines of 150 minutes per week of moderate to vigorous PA at 6-month follow-up, with 42% (8/19) of the intervention participants meeting the PA guidelines versus 27% (4/15) of the control participants (odds ratio 3.22, 95% CI 0.95-13.69). Exploratory analyses suggested conditional effects on PA outcomes based on baseline stage of motivational readiness, employment, and neighborhood safety., Conclusions: The PA intervention demonstrated feasibility and acceptability. Results of this pilot study indicate that the Hombres Saludables intervention is promising for increasing PA in Latino men and suggest that a fully powered trial is warranted. Our technology-based PA intervention provides a potentially scalable approach that can improve health in a population that is disproportionately affected by low PA and related chronic disease., Trial Registration: ClinicalTrials.gov NCT03196570; https://classic.clinicaltrials.gov/ct2/show/NCT03196570., International Registered Report Identifier (irrid): RR2-10.2196/23690., (©Akilah J Dulin, Shira Dunsiger, Tanya Benitez, Britta Larsen, Bess H Marcus, Gregory Champion, Kim M Gans. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 07.12.2023.)

Subthreshold depressive symptoms are highly prevalent among older adults and are associated with numerous health risks including cognitive decline and decreased physical health. One brain region central to neuroanatomical models of depressive disorders is the anterior cingulate cortex (ACC). The rostral portion of the ACC-comprised of the pregenual ACC and subgenual ACC-is implicated in emotion control and reward processing. The goal of the current study was to examine how functional connectivity in subregions of the rostral ACC relate to depressive symptoms, measured by the Beck Depression Inventory-Second Edition, in an ethnically diverse sample of 28 community-dwelling older adults. Based on meta -analyses of previous studies in primarily young adults with clinical depression, we hypothesized that greater depressive symptoms would be associated with primarily increased resting-state functional connectivity from both the subgenual ACC and pregenual ACC to default mode network regions and the dorsolateral PFC. We instead found that higher depressive symptoms were associated with lower functional connectivity of the ACC to the dorsolateral PFC and regions within the default mode network, including from the subgenual ACC to the dorsolateral PFC and anterior cingulate and from the pregenual ACC to the middle cingulate gyrus. This preliminary study highlights brain alterations at subthreshold levels of depressive symptoms in older adults, which could serve as targets for interventions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies arising from the bone marrow. Despite recent advances in treating these diseases, patients with higher-risk MDS and AML continue to have a poor prognosis with limited survival. It has long been recognized that there is an immune component to the pathogenesis of MDS and AML, but until recently, immune therapies have played a limited role in treating these diseases. Immune suppressive therapy exhibits durable clinical responses in selected patients with MDS, but the question of which patients are most suitable for this treatment remains unclear. Over the past decade, there has been remarkable progress in identifying genomic features of MDS and AML, which has led to an improved discernment of the molecular pathogenesis of these diseases. An improved understanding of immune and inflammatory molecular mechanisms of MDS and AML have also recently revealed novel therapeutic targets. Emerging treatments for MDS and AML include monoclonal antibodies such as immune checkpoint inhibitors, bispecific T-cell-engaging antibodies, antibody drug conjugates, vaccine therapies, and cellular therapeutics including chimeric antigen receptor T-cells and NK cells. In this review, we provide an overview of the current understanding of immune dysregulation in MDS and AML and an update on novel immune therapies for these bone marrow malignancies.

Bone marrow failure is characterized by a disruption of hematopoietic stem cell (HSC) homeostasis and function, which causes decreased blood counts. Germline and somatic mutations within HSCs and immune dysregulation contribute to the pathogenesis of marrow failure. Allogeneic HSC transplant is a potentially curative therapy for marrow failure, although not all patients are candidates for this procedure. Immune suppressive therapy (IST) is an effective treatment for patients with aplastic anemia (AA) and select patients with myelodysplastic syndromes, but some patients fail to respond or relapse after IST. Over the past decade, the oral thrombopoietin receptor agonist eltrombopag has become a therapeutic option for AA in combination with frontline IST, and as a single agent for relapsed and refractory patients after IST. In this review, we highlight current knowledge of thrombopoietin receptor agonist mechanisms of action, and clinical indications and toxicities in patients with marrow failure, including the risk of clonal evolution., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Latino men in the United States report low physical activity (PA) levels and related health conditions (eg, diabetes and obesity). Engaging in regular PA can reduce the risk of chronic diseases and yield many health benefits; however, there is a paucity of interventions developed exclusively for Latino men., Objective: To address the need for culturally relevant PA interventions, this study aims to develop and evaluate Hombres Saludables, a 6-month theory-based, tailored web- and text message-based PA intervention in Spanish for Latino men. This protocol paper describes the study design, intervention, and evaluation methods for Hombres Saludables., Methods: Latino men aged 18-65 years were randomized to either the individually tailored PA internet intervention arm or the nutrition and wellness internet control arm. The PA intervention included 2 check-in phone calls; automated SMS text messages; a pedometer; a 6-month gym membership; access to a private Facebook group; and an interactive website with PA tracking, goal setting, and individually tailored PA content. The primary outcomes were feasibility, acceptability, and efficacy (minutes per week of total moderate-to-vigorous PA assessed via the ActiGraph GT3X+ accelerometer worn at the waist and 7-day physical activity recall at baseline and 6 months). Secondary outcomes examined potential moderators (eg, demographics, acculturation, and environmental variables) and mediators (eg, self-efficacy and cognitive and behavioral processes of change) of treatment effects at 6 months post randomization., Results: This study was funded in September 2016. Initial institutional review board approval was received in February 2017, and focus groups and intervention development were conducted from April 2017 to January 2018. Recruitment for the clinical trial was carried out from February 2018 to July 2019. Baseline data collection was carried out from February 2018 to October 2019, with a total of 43 participants randomized. Follow-up data were collected through April 2020. Data cleaning and analysis are ongoing., Conclusions: We developed and tested protocols for a highly accessible, culturally and linguistically relevant, theory-driven PA intervention for Latino men. Hombres Saludables used an innovative, interactive, web- and text message-based intervention for improving PA among Latino men, an underserved population at risk of low PA and related chronic disease. If the intervention demonstrates feasibility, acceptability, and preliminary efficacy, we will refine and evaluate it in a larger randomized control trial., Trial Registration: Clinicaltrials.gov: NCT03196570; https://clinicaltrials.gov/ct2/show/NCT03196570., International Registered Report Identifier (irrid): DERR1-10.2196/23690., (©Kim M Gans, Akilah Dulin, Vanessa Palomo, Tanya Benitez, Shira Dunsiger, Laura Dionne, Gregory Champion, Rachelle Edgar, Bess Marcus. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 29.01.2021.)

Background: Familial steroid-sensitive nephrotic syndrome (SSNS) is a rare condition. The disease pathophysiology remains elusive. However, bi-allelic mutations in the EMP2 gene were identified, and specific variations in HLA-DQA1 were linked to a high risk of developing the disease., Methods: Clinical data were analyzed in 59 SSNS families. EMP2 gene was sequenced in families with a potential autosomal recessive (AR) inheritance. Exome sequencing was performed in a subset of 13 families with potential AR inheritance. Two variations in HLA-DQA1 were genotyped in the whole cohort., Results: Transmission was compatible with an AR (n = 33) or autosomal dominant (AD, n = 26) inheritance, assuming that familial SSNS is a monogenic trait. Clinical features did not differ between AR and AD groups. All patients, including primary (n = 7) and secondary steroid resistant nephrotic syndrone (SRNS), (n = 13) were sensitive to additional immunosuppressive therapy. Both HLA-DQA1 variations were found to be highly linked to the disease (OR = 4.34 and OR = 4.89; p < 0.001). Exome sequencing did not reveal any pathogenic mutation, neither did EMP2 sequencing., Conclusions: Taken together, these results highlight the clinical and genetic heterogeneity in familial SSNS. Clinical findings sustain an immune origin in all patients, whatever the initial steroid-sensitivity. The absence of a variant shared by two families and the HLA-DQA1 variation enrichments suggest a complex mode of inheritance.

Dent disease classically combines low-molecular-weight proteinuria, hypercalciuria with nephrocalcinosis, and renal failure. Nephrotic range proteinuria, normal calciuria, and hypokalemia have been rarely reported. It is unknown whether the changes in phenotype observed over time are explained by a decrease in glomerular filtration rate (GFR) or whether there is any phenotype-genotype relationship. To answer this we retrospectively analyzed data from 109 male patients with CLCN5 mutations (Dent-1) and 9 patients with mutation of the OCRL gene (Dent-2). In Dent-1 disease, the estimated GFR decreased with age, by 1.0 to 1.6 ml/min per 1.73 m(2)/yr in the absence and presence of nephrocalcinosis, respectively, with no significant difference. Median values of low-molecular-weight proteinuria were in the nephrotic range and remained at the same level even in late renal disease. End-stage renal disease occurred in 12 patients, at a median age of 40 years. Hypercalciuria decreased with glomerular filtration and was absent in 40% of the patients under 30 and 85% of those over the age of 30. Hypophosphatemia did not resolve with age and calcitriol concentrations were in the upper normal range. Kalemia decreased with age, with half of the patients over the age of 18 presenting with hypokalemia. Thus, no phenotype/genotype correlation was observed in this cohort of patients with Dent disease., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Aim: This study aimed to analyze acute renal failure in perinatal asphyxia (PNA) of term newborns in a sub-Saharan urban health center., Patients and Methods: The study was prospective, conducted from 1st June to 30th November 2013 on term newborns hospitalized at the centre hospitalier universitaire pédiatrique Charles-de-Gaulle for PNA. Renal insufficiency (RI) was defined by a serum creatinine greater than or equal to 90 μmol/L., Results: Eighty-five PNA cases were included, or 19.8% of newborns hospitalized in the study period. The sex ratio was 2.1. Thirty-eight newborns (44.7%) had RI. Their creatinine averaged 153.8±96.6 μmol/L. Twenty-six of 38 (68.4%) had brain damage in Sarnat stage 2 and 12 (31.6%) stage 3. Twelve newborns with RI (31.6%) had seizures. Transfontanellar echography revealed an abnormality in 30 cases (78.9%) of RI. Of the 38 newborns with renal failure, albuminuria was found in 21 cases (65.2%) and leukocyturia in 28 cases (73.7%). Renal function improved in 86.1% of cases. Newborns with initially normal serum creatinine had no RI during hospitalization. Six newborns (7.1%) died., Conclusion: This study showed that acute RI is common during PNA most particularly in newborns with severe neurological impairment. In our context, earlier support for women in labor could help prevent PNA and therefore newborn acute RI., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Dent disease is a rare X-linked tubulopathy characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis and/or nephrolithiasis, progressive renal failure, and variable manifestations of other proximal tubule dysfunctions. It often progresses over a few decades to chronic renal insufficiency, and therefore molecular characterization is important to allow appropriate genetic counseling. Two genetic subtypes have been described to date: Dent disease 1 is caused by mutations of the CLCN5 gene, coding for the chloride/proton exchanger ClC-5; and Dent disease 2 by mutations of the OCRL gene, coding for the inositol polyphosphate 5-phosphatase OCRL-1. Herein, we review previously reported mutations (n = 192) and their associated phenotype in 377 male patients with Dent disease 1 and describe phenotype and novel (n = 42) and recurrent mutations (n = 24) in a large cohort of 117 Dent disease 1 patients belonging to 90 families. The novel missense and in-frame mutations described were mapped onto a three-dimensional homology model of the ClC-5 protein. This analysis suggests that these mutations affect the dimerization process, helix stability, or transport. The phenotype of our cohort patients supports and extends the phenotype that has been reported in smaller studies., (© 2015 WILEY PERIODICALS, INC.)

Aim: Rituximab is one of nine biologic agents approved for the treatment of rheumatoid arthritis (RA) in Australia. The primary study objective was to analyze the factors that lead to the therapeutic decision to use rituximab in RA., Method: A cross-sectional, retrospective chart review was conducted to identify patients who were treated with rituximab and to evaluate their response to treatment., Results: Factors influencing the prescription of rituximab were identified. The most commonly reported reason for prescribing rituximab was the presence of comorbidities and the presence of seropositive disease. Median rituximab treatment duration was 32.5 months and mean number of treatment cycles was 4.1. Disease activity scores showed significant improvement from baseline to most recent visit. Rituximab treatment was well-tolerated in this group of RA patients., Conclusions: Rituximab was effective in a refractory group of RA patients and appears to be safe in a population with a high prevalence of comorbidities, including malignancy and recurrent infections/bronchiectasis. This study may assist rheumatologists in selecting appropriately targeted therapy in RA., (© 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

GPB are often performed in PRT to detect subclinical acute rejection or IF/TA. Reducing immunosuppression side effects without increasing rejection is a major concern in PRT. We report the results of GPB in children transplanted with a steroid-sparing protocol adapted to immunological risk. Children under 18 yr who received a renal transplantation between April 1, 2009 and May 31, 2012 were included. Immunosuppression consisted of an antibody induction therapy, tacrolimus, and MMF for all recipients. CSs were administered to children under five yr old, or receiving a second allograft. Twenty-eight children were included, 50% were CSs free. GPB were performed between three and six months. IF/TA was documented in seven biopsies; four of these seven children were CS free. One child, with CSs, presented a borderline rejection, and another child, steroid free, with significant inflammatory interstitial infiltrate, considered as a subclinical rejection, was treated with CSs pulses. The median eGFR was stable (74, 67.5, and 82 mL/min/1.73 m² at, respectively, seven days, three months, and one yr). Patient and graft survival were 100%. These results have to be confirmed in a larger cohort, with long-term follow-up., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Antineutrophil cytoplasmic antibodies (ANCA) are usually considered as serological markers of vasculitis (microscopic polyangiitis, granulomatosis with polyangiitis, and Churg-Strauss syndrome), but they have also been described in other diseases. They are rarely observed in children. Therefore, this study aims to describe the clinical spectrum associated with positive ANCA in children., Patients and Methods: All the children below 15 years of age, admitted to the Angers University Hospital between June 2004 and June 2010 presenting with an ANCA-positive test by indirect immunofluorescence were included in this study. The exhaustive list of ANCA-positive children was obtained from the immunology unit. Six antigenic targets were routinely tested by Elisa, i.e., proteinase 3, myeloperoxidase, bactericidal permeability increasing protein, cathepsin G, elastase, and lactoferrin. Clinical and biological data were retrospectively collected., Results: Thirty-seven children were identified with positive ANCA in this 6-year period. None of the antigenic targets tested was found in 21 patients. The most frequent diseases associated were inflammatory bowel disease (n=10), infections (n=6), hematological disease (n=5), and juvenile idiopathic arthritis (JIA) (n=4). Patients with JIA presented with a predominance of antielastase antibodies., Conclusion: In contrast to the findings usually observed in adults, we obtained a wide spectrum of clinical entities associated with positive ANCA in this cohort. In children, the ANCA test has 2 advantages: to diagnose systemic vasculitis and to differentiate inflammatory bowel disease. Patients with JIA seemed to have more frequent antielastase antibodies: in the future, this finding should be further investigated in larger prospective studies., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Urinary tract infection (UTI) is one of the most common infections in children but Haemophilus is rarely involved. In our institution, only 3 children below the age of 15 years presented with UTI due to Haemophilus influenzae between January 2010 and October 2011. These children had typical symptoms of UTI: fever, abdominal pain and dysuria. In all 3 patients, standard urinalysis remained negative, but H. influenzae was found after bacterial growth in special media, i.e., blood agar (or chocolate agar). These patients had abnormalities of the urinary tract. The first patient, a 5-year-old girl, had a right ureteropelvic junction syndrome found after her UTI. The second, a 4-year-old girl, had a bilateral ureteral duplication found after many UTIs. The third, a 2-month-old boy, had a right ureteropelvic junction syndrome that had been diagnosed by prenatal ultrasound. In our hospital, during the study period, the prevalence of UTI caused by Haemophilus was 0.02% of all pediatric UTIs. There are few reports in the literature on UTI caused by Haemophilus in children (<1%): they are frequently associated with urinary tract abnormalities. The bacterium is not able to grow in usual media, so that when there is a clinical UTI with Gram negative bacilli on the direct exam but not found in the culture, an infection with Haemophilus should be discussed, and blood agar used, which is all the more important when there are underlying abnormalities of the urinary tract., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Dent's syndrome is a rare inherited tubulopathy. Factors influencing renal function in this disease are not well known. The aim of our study is to investigate the evolution of the Dent's syndrome in renal plan. The study was retrospective and conducted in 2006, concerning four brothers. The genetic defect was a mutation S244L missense in exon 6 of gene CLCN5. Various parameters were studied. Patients were 8.5 to 21-years-old at the beginning of the follow-up. Two of them had chronic renal insufficiency (CRI) which evolved, at least 7 years of moderate to terminal stage. Tubular signs were made of hypokalemia, hypercalciuria, hypophosphatemia and proteinuria mostly β2 microglobulin. Improvement of these abnormalities was obtained with symptomatic treatment which has not always been well tolerated. A case of beginner nephrocalcinosis was observed. There was size and weight delay at the beginning of patient monitoring. Dent's syndrome may be complicated by CRI. It seems to appear in the second decade of life and hypercalciuria would contribute to it. Our CRI patients had significant bone disease. The hypercalciuria and proteinuria are factors over which we try to act. Clinical trials are needed to evaluate the efficacy of treatment on the reduction of CRI or its progression by reducing these factors in patients with Dent's syndrome., (Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

This case study describes a patient who developed peanut allergy following lung transplantation. A 54-year-old woman underwent bilateral lung transplantation on June 2009 owing to severe chronic obstructive pulmonary disease. She had no history of food allergy before transplantation. The donor, however, was a 20-year-old man who was fatally injured during an automobile accident; he was allergic to peanuts. At 3 months after transplantation, the lung recipient presented with acute dyspnea and urticaria 15 minutes after consuming food containing peanut derivatives. Pre- and posttransplantation recipient blood samples analyzed for the presence of IgE antibodies specific for peanut allergens confirmed that the allergy had been passively transfered as a consequence of transplantation. Food allergy following solid organ transplantation is thought to be rare, mostly occurring in children. Two mechanisms may explain the observations described for the patient reported in this study: de novo development of peanut allergies after transplantation, or passive transfer of peanut allergies from a peanut-sensitized organ donor. This case report documenting pre- and posttransplantation IgE status in a lung transplantation case suggested that the allergic status of organ donors should be thoroughly assessed before transplantation, and potential allergy transfer risks must be discussed with the transplant team and the patient., (Copyright © 2011 Elsevier Inc. All rights reserved.)

X-ray absorption spectra at the Co L(2,3)-edges were analyzed by means of ligand field multiplet calculations in different states of three photomagnetic CoFe Prussian blue analogues of chemical formula Cs(2)Co(4)[Fe(CN)(6)](3.3) x 11 H(2)O, Rb(2)Co(4)[Fe(CN)(6)](3.3) x 11 H(2)O and Na(2)Co(4)[Fe(CN)(6)](3.3) x 11 H(2)O. These simulations of the experimental spectra allowed the quantification of the crystal field parameter (10Dq). This determination led us (i) to evidence different behaviors of the Co(III)(LS) and Co(II)(HS) ions in the three-dimensional structure related to their electronic configurations, (ii) to propose an approach based on the electronic density distribution along the Co-NC-Fe linkage to account for the energy position of the states implied in the switching properties of the compounds, and (iii) to explain the different photomagnetic properties observed as a function of the size of the inserted alkali cation by competing interactions between the cyanide ion and the transition metal ions within the CoFe cyanide bimetallic network on the one hand and the cyanide ion and the alkali metal ions on the other hand.

Documentation of early human migrations through Island Southeast Asia and Wallacea en route to Australia has always been problematic due to a lack of well-dated human skeletal remains. The best known modern humans are from Niah Cave in Borneo (40-42ka), and from Tabon Cave on the island of Palawan, southwest Philippines (47+/-11ka). The discovery of Homo floresiensis on the island of Flores in eastern Indonesia has also highlighted the possibilities of identifying new hominin species on islands in the region. Here, we report the discovery of a human third metatarsal from Callao Cave in northern Luzon. Direct dating of the specimen using U-series ablation has provided a minimum age estimate of 66.7+/-1ka, making it the oldest known human fossil in the Philippines. Its morphological features, as well as size and shape characteristics, indicate that the Callao metatarsal definitely belongs to the genus Homo. Morphometric analysis of the Callao metatarsal indicates that it has a gracile structure, close to that observed in other small-bodied Homo sapiens. Interestingly, the Callao metatarsal also falls within the morphological and size ranges of Homo habilis and H. floresiensis. Identifying whether the metatarsal represents the earliest record of H. sapiens so far recorded anywhere east of Wallace's Line requires further archaeological research, but its presence on the isolated island of Luzon over 65,000 years ago further demonstrates the abilities of humans to make open ocean crossings in the Late Pleistocene.

Background and Objectives: Neurologic involvement is the most threatening complication of diarrhea-associated hemolytic uremic syndrome (D+HUS)., Design, Setting, Participants, & Measurements: We report a retrospective multicenter series of 52 patients with severe initial neurologic involvement that occurred in the course of D+HUS., Results: Verotoxigenic Escherichia coli infection was documented in 24. All except two patients had acute renal failure that required peritoneal dialysis, hemodialysis, or both techniques. A first group of eight patients remained with normal consciousness; five of them had protracted seizures. A second group of 23 patients had stuporous coma; five of these had protracted severe seizures, and 18 had a neurologic defect including pyramidal syndrome, hemiplegia or hemiparesia, and extrapyramidal syndrome. A third group of 21 patients had severe coma. Plasma exchanges were undertaken in 25 patients, 11 of whom were treated within 24 hours after the first neurologic sign; four died, two survived with severe sequelae, and five were alive without neurologic defect. Magnetic resonance imaging (MRI) for 29 patients showed that (1) every structure of the central nervous system was susceptible to involvement; (2) no correlation seemed to exist between special profile of localization on early MRI and the final prognosis; and (3) MRI did not exhibit any focal lesions in three patients. The overall prognosis of the series was marked by the death of nine patients and severe sequelae in 13., Conclusions: Neurologic involvement is associated with a severe renal disease but does not lead systematically to death or severe disability.

Primary hyperoxaluria type 1 results from alanine:glyoxylate aminotransferase deficiency. Due to genotype/phenotype heterogeneity in this autosomal recessive disorder, the renal outcome is difficult to predict in these patients and the long-term impact of conservative management in children is unknown. We report here a multicenter retrospective study on the renal outcome in 27 affected children whose biological diagnosis was based on either decreased enzyme activity or identification of mutations in the patient or his siblings. The median age at first symptoms was 2.4 years while that at initiation of conservative treatment was 4.1 years; 6 children were diagnosed upon family screening. The median follow-up was 8.7 years. At diagnosis, 15 patients had an estimated glomerular filtration rate (eGFR) below 90, and 7 children already had stage 2-3 chronic kidney disease. The median baseline eGFR was 74, which rose to 114 with management in the 22 patients who did not require renal replacement therapy. Overall, 20 patients had a stable eGFR, however, 7 exhibited a decline in eGFR of over 20 during the study period. In a Cox regression model, the only variable significantly associated with deterioration of renal function was therapeutic delay with a relative risk of 1.7 per year. Our study strongly suggests that early and aggressive conservative management may preserve renal function of compliant children with this disorder, thereby avoiding dialysis and postponing transplantation.

Current therapy for congenital nephrogenic diabetes insipidus consists of appropriate water intake coupled with decreased urine output obtained by means of a low-sodium diet and a combination of thiazide diuretics with renal prostaglandins inhibitors or amiloride. We report a case of congenital nephrogenic diabetes insipidus that was complicated by paradoxical water intoxication secondary to liberal water intake and the initiation of hydrochlorothiazide and indomethacin combination therapy. This report emphasizes the importance of evaluating the water balance and of a quick response with strict protocols following the initiation of indomethacin and thiazide diuretics in nephrogenic diabetes insipidus.

Purpose: Antibiotic prophylaxis is given to children at risk for urinary tract infection. However, evidence concerning its effectiveness in grade I to III vesicoureteral reflux is lacking. The objective of this study was to determine whether antibiotic prophylaxis reduces the incidence of urinary tract infection in young children with low grade vesicoureteral reflux., Materials and Methods: Children 1 month to 3 years old with grade I to III vesicoureteral reflux were assigned randomly to receive daily cotrimoxazole or no treatment, and followed for 18 months. A urinary tract infection constituted an exit criterion. Infection-free survival rates were calculated using the Kaplan-Meier method and compared using the log rank test., Results: A total of 225 children were enrolled in the study. Distribution of gender, age at inclusion and reflux grade were similar between the 2 groups. There was no significant difference in the occurrence of urinary tract infection between the 2 groups (17% vs 26%, p = 0.2). However, a significant association was found between treatment and patient gender (p = 0.017). Prophylaxis significantly reduced urinary tract infection in boys (p = 0.013), most notably in boys with grade III vesicoureteral reflux (p = 0.042)., Conclusions: These data suggest that antibiotic prophylaxis does not reduce the overall incidence of urinary tract infection in children with low grade vesicoureteral reflux. However, such a strategy may prevent further urinary tract infection in boys with grade III reflux.

Cerebello-oculo-renal syndrome (CORS), also called Joubert syndrome type B, and Meckel (MKS) syndrome belong to the group of developmental autosomal recessive disorders that are associated with primary cilium dysfunction. Using SNP mapping, we identified missense and truncating mutations in RPGRIP1L (KIAA1005) in both CORS and MKS, and we show that inactivation of the mouse ortholog Rpgrip1l (Ftm) recapitulates the cerebral, renal and hepatic defects of CORS and MKS. In addition, we show that RPGRIP1L colocalizes at the basal body and centrosomes with the protein products of both NPHP6 and NPHP4, known genes associated with MKS, CORS and nephronophthisis (a related renal disorder and ciliopathy). In addition, the RPGRIP1L missense mutations found in CORS individuals diminishes the interaction between RPGRIP1L and nephrocystin-4. Our findings show that mutations in RPGRIP1L can cause the multiorgan phenotypic abnormalities found in CORS or MKS, which therefore represent a continuum of the same underlying disorder.

Objectives/hypothesis: The objectives of this study were to 1) quantify the relative importance of established risk factors for congenital hearing loss (HL), 2) identify other risk factors for congenital HL, and 3) create a prognostic system that can predict the chance of an infant having HL., Methods: The authors conducted a retrospective cohort study with validation of a prognostic system. The authors used a medical record review on 1,863 infants admitted to level II and level III nurseries who underwent auditory brainstem reflex (ABR) hearing screening from 1998 to 1999 (derivation cohort). The primary outcome was hearing screening referral (i.e., hearing screening failure) classified as mild to moderate, moderate to severe, and severe to profound loss. To validate the prognostic system, a medical record review of a separate cohort of 437 infants admitted to a level III nursery who underwent ABR hearing screening in 2002 (validation cohort) was performed., Results: In the derivation cohort, 1,513 infants (81%) passed the ABR screen at 30 dB, 77 (4%) had a unilateral referral, 243 (13%) had a bilateral referral, and 30 (1.6%) did not have a complete screening. In multivariable analysis, the following risk factors were clinically and statistically significant: craniofacial abnormalities, cytomegalovirus infection, bronchopulmonary dysplasia (BPD), maternal ethanol use, syndromes, hydrocephalus, and hyperbilirubinemia., Conclusions: Our results reaffirm the importance of several established risk factors for congenital HL, but suggest that BPD is an important predictor in high-risk populations. Whether these risk factors are causal or merely associated in congenital HL remains to be determined.

We report here the X-ray magnetic circular dichroism (XMCD) study at the Gd M(4,5)- and L(2,3)-edges of two linear magnetic chains involving Gd(III) cations bridged by nitronyl nitroxide radicals. This spectroscopy directly probes the magnetic moments of the 4f and 5d orbitals of the gadolinium ions. We compare macroscopic magnetic measurements and local XMCD signals. The M(4,5)-edges results are in agreement with the J values extracted from the fits of the SQUID magnetic measurements. The L(2,3)-edges signals show that the electronic density in the Gd 5d orbitals depends on the neighbors of the gadolinium cations. Nevertheless, the 5d orbitals do not seem to play any role in the superexchange pathway between radicals through the metal ion proposed to explain the particular magnetic exchange interactions between the radicals in these chains.

Objectives: The aim of this study was to describe the intensive care unit neonatologists' attitudes about a neonate with terminal or pre-terminal renal failure., Methods: A questionnaire was sent to all French neonatal intensive care units. Physicians were asked to describe their attitude about neonatal chronic renal failure (Would you agree with dialysis and graft for these children?). Physicians were also presented with two clinical observations involving neonates with varying degrees of renal insufficiency and a complicating comorbidity, including neurological abnormality or socioeconomic circumstances., Results: Responses were obtained from 92% of the university neonatal care units. The will to take care of a neonate with end-stage renal failure till the renal graft, varied greatly from a centre to another one. Three (9%) university-teams said they had a strong will to bring the baby from the neonatal period to the time of renal graft. Eleven other centres (32%) did not have any will for accompanying the baby till the renal graft. Eight centres (24%) would be rather favourable to the idea of dialysis and graft, and 12 others (35%) would be rather unfavourable., Conclusion: The results of this study show great differences between French neonatologists when they are faced to newborns with end stage renal failure. Ethical, medical and organisational difficulties are matters of controversy. The epidemiological impact of the perinatal discussion could be a 20% variation of all the renal grafts in children.

In Part 2 of this work, the electronic and local structure of the photoinduced metastable magnetic state of the Prussian blue analogue Rb1.8Co4[Fe(CN)6]3.3-13H2O were characterized. To determine directly the relative orientation of the magnetic moments of Co(II) and Fe(III) ions in the metastable state, and the nature of the exchange interaction between them, we performed X-ray magnetic circular dichroism (XMCD) experiments at the cobalt and iron K edges. We present the first direct experimental evidence of the antiferromagnetic interaction between the cobalt and the iron ions, leading to the ferrimagnetism of the photoinduced metastable state.

Shigellae infect human intestine and cause intense inflammation and destruction of colonic and rectal mucosa. To model the interactions of shigella with human intestine in vivo, we have studied shigella infection in human intestinal xenografts in severe combined immunodeficient mice (SCID-HU-INT mice). Inoculation of shigella into human intestinal xenografts caused severe inflammation and mucosal damage, which was apparent as soon as 4 h following infection. Shigella infection was associated with human intestinal production of interleukin-1B (IL-1B) and IL-8 and a marked neutrophil influx into the graft. Depletion of neutrophils from SCID-HU-INT mice reduced inflammation in the human intestinal xenograft in response to shigella infection but failed to significantly alter tissue damage. However, the number of intracellular bacteria was more than 20-fold higher in the human intestinal xenografts from neutrophil-depleted SCID-HU-INT mice. Infection of human intestinal xenografts with an attenuated vaccine strain of shigella (CVD1203) induced lower levels of IL-1B and IL-8 than wild-type shigella and caused only moderate damage to the intestinal permeability barrier. Our studies establish the SCID-HU-INT mouse as a viable model for studying the interactions between shigella and human intestine and indicate that neutrophils are important for controlling the invasion of human intestine by shigella.

The coexistence of anti-La (SS-B) and anti-Ro (SS-A) autoantibodies in pSS is probably explained by intermolecular spreading of autoimmunity toward different components of the La/Ro ribonucleoprotein (RNP). In order to evaluate the role of the HLA class II phenotype in controlling diversification of this autoantibody response, 80 patients with pSS were typed by polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) at the HLA class II loci DRB1, DQA1 and DQB1. Serum samples were examined for anti-La and anti-Ro by counterimmunoelectrophoresis and by ELISA using purified recombinant La and 60-kD Ro proteins. Patient sera were classified according to the extent of diversification of the anti-La, anti-Ro response including the presence or absence of precipitating anti-La antibodies. Immunogenic characteristics of these stratified groups were then studied. All patients with pSS, with or without autoantibodies to Ro and La, were found to have at least one of the HLA-DRB1 types DR2, DR3 or DR5. The HLA DR3-DQA1*0501-DQB1*02 (DR3-DQ2) haplotype was primarily associated with a diversified La/Ro RNP response containing precipitating autoantibodies to La (P<0.001); whereas the haplotype HLA DR2-DQA1*0102-DQB1*0602 (DR2-DQ1) was associated with a less diversified La/Ro RNP response containing non-precipitating (restricted epitope) anti-La autoantibodies (P<0.001). Anti-La-positive patients lacking both HLA-DR2 and HLA-DR3 all expressed the HLA-DQA1*0501 allele, which was present at increasing frequency with greater diversification of the anti-La/Ro autoantibody response. The association of distinct HLA haplotypes with different degrees of autoantibody diversification in patients with pSS suggests a model of HLA-restricted presentation of La/Ro peptide determinants to autoreactive helper T cells. We propose that non-precipitating anti-La responses are driven by limited intermolecular help from DR2-DQ1-restricted T helper cells recognizing Ro determinants. On the other hand, we speculate that the more diversified, precipitating anti-La responses obtain more efficient cognate T help from DR3-DQ2-restricted T helper cells recognizing La determinants, where HLA-DQA1*0501 may be a critical determinant for antigen presentation.

Mutations in the CLCN5 gene, mapped in Xp11.22, have been recently reported to be associated with X-linked nephrolithiasis, X-linked recessive hypophosphataemic rickets and Dent's disease. We report a missense mutation in exon 6 of the CLCN5 gene. The mutation in this pedigree is S244L, the same mutation as has previously been described in an Italian family showing a similar pathology. However, in the family reported here, affected males have developed neither nephrolithiasis nor nephrocalcinosis. The question arises whether we are dealing with a milder phenotype or whether a more severe pathology will develop with ageing.

We report an intestinal pseudo-obstruction syndrome occurring in a 6-month-old infant girl suffering from acquired major and persistent abdominal distension, which 2 months later required ileostomy. Histologic examination of samples of the small intestine showed considerable inflammatory reaction in the muscular layers of the intestinal wall. Steroid therapy, begun as soon as the histologic results were known, resulted in recovery. In a similar case, reported previously, steroid therapy used after the lesions had already caused fibrosis and atrophy of the intestinal wall, proved ineffective. This particular form of pseudo-obstruction is classified as "idiopathic myositis of the small intestine." It is important to identify the condition because an early course of steroid therapy, before the appearance of fibrotic lesions, could improve the prognosis.

Unlabelled: Malformative uropathies diagnosed in utero are increasing in number. This work describes the decision strategy adopted in Angers concerning the neonatal handling of those abnormalities., Patients and Methods: One hundred children born between 1988 and 1990, with prenatally suspected fetal uropathy, were included in the study and followed for a period of 3 years. In every case, an ultrasound scan was performed at birth. In cases with persistent abnormality, a voiding cystourethrography was done in the first week of life. An intravenous urograph and/or a nuclear renography were performed during the second month of life., Results: Twenty-nine children were normal. Seventy-one were affected by 126 isolated or related uropathies; the most frequent ones were the ureteropelvic junction obstruction syndrome (48), ureterovesical junction obstruction (18) and multicystic kidneys (13). A vesicoureteral reflux was associated in 22% of cases. The diagnosis was perfectly correlated with the prenatal diagnosis in 50% of cases. Fourteen of the normal children had a later ultrasound scan control, between 2 and 9 months; later on, three of them showed a moderate ureteropelvic junction obstruction syndrome. Amongst the 48 ureteropelvic junction obstruction syndromes, 22% have been operated on. The others obstructive uropathies remained stable or spontaneously improved., Discussion: These results require us to discuss as matter of priority the large number of spontaneously regressive prenatal hydronephrosis and the necessity to establish a consensus for the pre and postnatal pathological thresholds of the anteroposterior pelvic diameter, the interest in carrying out a voiding cystography after the birth when dilatation is confirmed, the interest of nuclear renography for the diagnosis and follow-up of obstructive uropathies and the absence of urgency for surgery., Conclusion: We propose a decision tree specifying the action to take when facing the diagnosis of a prenatal hydronephrosis. It could be a part of the reflection for the medical teams handling these uropathies is the aim of a consensual attitude which is now essential.

Background/aims: Several reports suggest that duodenogastroesophageal reflux may produce esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. The purpose of this study was to understand better the relationship of pH (< 4 and > 7), duodenogastroesophageal reflux, and fasting bile acid concentrations in producing esophageal damage., Methods: Using a spectrophotometric technique to measure bile reflux, four groups were studied: healthy subjects, reflux patients, patients with Barrett's esophagus, and patients with esophageal symptoms after partial gastrectomy., Results: Simultaneous 24-hour pH and bile monitoring of distal esophagus found close association between total percent of time pH < 4 and duodenogastroesophageal reflux (r = 0.78; P < 0.001) but a poor relationship (r = -0.06) with total percent of time pH > 7, suggesting that the term alkaline reflux is a misnomer. Duodenogastroesophageal reflux increased significantly with the severity of reflux disease, being greatest in patients with Barrett's esophagus and comparable with that in patients with partial gastrectomy. Fasting bile acid concentrations did not distinguish patients with Barrett's esophagus from those with reflux. Rather, increased quantity of acid reflux was the single factor most characterizing patients with Barrett's esophagus. Omeprazole (20 mg twice daily) normalized acid reflux parameters (13.8% +/- 1.6% to 0.8% +/- 0.6%) and significantly (P < 0.001) decreased duodenogastroesophageal reflux (32.8% +/- 6.9% to 4.7% +/- 1.7%)., Conclusions: Acid reflux is the primary factor in the development of Barrett's esophagus. Bile reflux parallels acid reflux and, at best, may have a synergistic role. Aggressive acid suppression with omeprazole markedly decreases both.

Objective: To conduct a retrospective analysis of one center's experience with treating achalasia over 4 yr with skilled gastroenterologists using primarily the Rigiflex balloon dilator and with a senior surgeon performing Heller myotomies., Methods: Newly diagnosed cases of achalasia were identified by a computer search of hospital records. Charts were reviewed for the presence/severity of dysphagia, regurgitation, heartburn, and chest pain. Weight loss was also recorded. Esophageal manometries and barium swallows were reviewed. Choice of treatment was made freely by patients. With an a priori definition of success, follow-up was conducted by telephone interviews., Results: A total of 45 achalasia patients (mean age, 46 yr; 32 females, 13 males) were identified with a symptoms-frequency as follows: dysphagia, 100%; regurgitation, 78%; heartburn, 50%; and chest pain, 42%. Mean weight loss was 17.5 pounds. Primary treatment was pneumatic dilation in 36 patients and surgery in nine patients. In a total of 45 pneumatic dilations, three (6.6%) were complicated by perforation. Five (14%) patients required repeat dilation. Mean duration of follow-up for pneumatic dilation and surgery was 27 months and 20.8 months, respectively. The overall excellent-good success rates were: pneumatic dilation 88% and surgery 89%. In comparing the efficacy of pneumatic dilation versus surgery, all symptoms were improved significantly (p < 0.01) in both groups, except heartburn, which increased postmyotomy., Conclusions: If both procedures are available by skilled operators, pneumatic dilation and surgery are equally effective in the treatment of achalasia.

Background/aims: Although dysphagia in patients with peptic stricture is attributed to a decreased luminal diameter, coexistent esophagitis may be an equally important cause. The goals of this study were to determine whether medical healing of esophagitis in patients with stricture improves dysphagia and decreases dilatation need and to compare the efficacy and cost-effectiveness of omeprazole versus H2-receptor antagonists (H2RA)., Methods: Thirty-four dysphagic patients with peptic stricture and erosive esophagitis were dilated and randomized to omeprazole 20 mg every day versus H2RA (ranitidine 150 mg twice daily or famotidine 20 mg twice daily). Patients received further dilatations only if dysphagia frequency was greater than or equal to once per week. At 3 and 6 months, patients were assessed for esophagitis healing, dysphagia relief, and bougienage requirements. Cost-effectiveness of omeprazole and H2RA was determined., Results: Patients with healed esophagitis at 3 and 6 months were more likely to dysphagia-free and to require fewer dilatations than patients with persistent esophagitis. At 6 months, omeprazole produced a significantly (P < 0.01) higher rate of esophagitis healing, dysphagia relief, and fewer dilatations compared with H2RA. Omeprazole was also 40%-50% more cost-effective., Conclusions: Esophagitis healing improves dysphagia and decreases dilatation need in patients with peptic stricture. Omeprazole heals esophagitis and relieves dysphagia more efficaciously than H2RA while decreasing costs to patients.

Erythromycin, a possible motilin agonist, is a potent gastrokinetic agent that may increase the lower esophageal sphincter pressure. Therefore, we assessed the effects of erythromycin in two dosages (250 and 500 mg per os four times a day) on esophageal pH and pressure profiles in reflux patients using prolonged ambulatory monitoring systems. Studies were blinded, placebo-controlled with randomized crossover design. Patients took each drug for three days prior to studies, with erythromycin serum levels obtained the day of esophageal studies. Erythromycin 250 mg four times a day had no effect on esophageal contraction pressures or peristalsis during the day or meal periods. In the supine position, however, erythromycin significantly (P = 0.012) decreased esophageal contraction velocity and showed a strong trend (P = 0.059) towards increasing the percentage of peristaltic waves. Despite these potentially beneficial effects on esophageal clearance, no significant difference in acid exposure times during 24-hr pH studies were observed between placebo and low-dose erythromycin. High-dose erythromycin (500 mg four times a day) was associated with drug levels in the typical antibiotic efficacy range (normal 1-3 micrograms/ml; patients 1.7-7.0 micrograms/ml), but, here again, there was no significant difference in all acid reflux parameters between placebo and erythromycin phases. Therefore, "standard" doses of erythromycin have no important clinical effects on esophageal pressures or acid reflux parameters.

A case of hypothalamic dysfunction in a girl with a twelve-year follow-up is reported. Onset occurred at the age of three with severe obesity, hypothermia, hypersomnia, and lethargy. Somatotropic, gonadotropic, and thyrotropic hormones were low, whereas prolactin was increased. Imaging techniques failed to disclose any lesion of the hypothalamus or pituitary. Clomipramine improved the vegetative disorders. The literature on clinical and hormonal disorders of hypothalamic dysfunction is reviewed.

To test the hypothesis that early steroid pulsing augments the efficacy and decreases the toxicity of chrysotherapy 40 patients with rheumatoid arthritis were studied in a double blind, placebo controlled study. During the first three months of gold treatment group 1 received monthly intravenous methylprednisolone pulsing (steroid group) while group 2 received placebo (placebo group). All patients were assessed clinically and serologically over a 24 week period. Twelve patients were withdrawn before completion of the study and all but one of the remaining 28 patients reported clinical and serological improvements. Two patients in the steroid group were withdrawn owing to gold induced side effects while four were withdrawn in the placebo group. These small numbers were not significantly different. Minor side effects occurred more commonly in the placebo group. The clinical response was clearly better in the steroid group with statistical significance almost being achieved. In an endeavour to obtain a significant conclusion further patients will now be entered into this study.

Inherited adenine phosphoribosyltransferase (APRT) has a recessive transmission. When it is very important, adenine can't be restored into nucleic acids pool and will changed into 2,8-dihydroxyadenine (2,8-DHA) by xanthine oxidase. To date in all countries but Japan, 2,8-DHA urolithiasis is observed only into homozygotic subjects with complete APRT deficiency Commonly, its onset is observed in childhood often dramatically. The authors report two new pediatric cases into new french families. First a 8 years old boy with spontaneous elimination of two lithiasis after right lumbar pain. Secondly an infant (nineteen months) who has presented an acute renal failure with anuria. Bilateral lithiasis included into pyelourectal junctions have been pulled out by bilateral surgical pyelotomy. In each case, lithiasis were radiolucent and diagnosis made by ultrasonography. The uric acid metabolism was normal and it is the infra red spectrophotometric study of stones that had recognised the 2,8-DHA component. In the second case, bilateral residual lithiasis have been broken by piezoelectric extra-corporeal lithotripsy with good tolerance and favorable result. The two children received preventive treatment. After 36 and 19 months they have no recurrence. In the literature, the frequency of 2,8-DHA lithiasis is very more low than the theoretical of homozygotics in population (1/100,000). The common confusion with uric lithiasis is one possible explanation. So spectrophotometric study of radiolucent stones was meant to be realised when uric metabolism is not disturbed.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors report eight cases of severe neonatal infections with Coxsackie and Echo virus. Meningo-encephalitis, aseptic meningitis, myocarditis and sepsis-like state were the most frequent presenting conditions. A high mortality rate was associated with meningo-encephalitis and low birth weight.

To investigate the capacity of bacterial filters to prevent complications of the central venous nutrition in neonates, 100 percutaneous central catheters were placed in 94 neonates: 50 catheters was used with a bacterial filter and 50 without filter. No significant difference appeared between the 2 groups for the frequency of complications. Complications should be avoided with a rigorous technique in the maintenance.

A study was done of 15 children and adolescents, aged 2.5 to 17.5 years, who were treated by continuous ambulatory peritoneal dialysis (CAPD) for 6 to 24 months. Plasma albumin concentration decreased from 34.4 +/- 4.8 g/liter at the onset of therapy to 31.3 +/- 5.3 g/liter after 19 to 24 months. Children less than 6 years old had lower albumin levels (29.4 +/- 1.7 g/liter) than did the older group (36.3 +/- 4.2 g/liter). The lower plasma albumin was related to peritoneal protein loss but not to protein intake. Plasma free amino acid concentrations were not significantly modified. No changes occurred in the oral glucose tolerance test during the course of CAPD. Plasma cholesterol and triglycerides were abnormally high for age, with a correlation seen between cholesterolemia and peritoneal protein loss.