Barnabás Rózsai

Urinary cytokine response to asymptomatic bacteriuria in type 1 diabetic children and young adults

Abstract:  It has been reported that urinary interleukin‐6 (IL‐6) and IL‐8 levels are decreased in adult diabetic women with asymptomatic bacteriuria (ASB) when compared with non‐diabetic women with ASB. Such impaired cytokine excretion might play a role in the higher prevalence of ASB among diabetic subjects. The aim of this study was to examine the urinary IL profile in children and young adults with type 1 diabetes mellitus (T1DM) with and without ASB. Midstream clean voiding urine samples were collected and cultured from 133 patients with T1DM (age: 15.6 ± 5.7 yr) and 178 controls (14.1 ± 4.7 yr) for two consecutive days. ASB was diagnosed in the case of ≥105 bacteria/mL. The urinary IL‐6 and IL‐8 concentrations were determined, and the presence of leukocyturia was also recorded. The prevalence of ASB was 16.5% in diabetic subjects and 2.8% in controls (p = 0.001). There was no difference between the diabetic and the control groups in the prevalence of ‘IL‐6‐uria’ (21.9 vs. 18.0%; p = 0.41), but IL‐8 was more frequently detectable in the diabetic group (47.4 vs. 27.5%; p = 0.001). In individuals with ASB, the IL‐8 level was similar in the diabetic (median: 70.0 pg/mg creatinine) and control group (42.3 pg/mg creatinine; p = 0.8). Indeed, the IL‐8 levels were higher in diabetic subjects with ASB as compared with those without it (70.0 vs. <3.1 pg/mg creatinine; p = 0.001), and there was a significant association between the urinary IL‐8 concentration and the bacterial count (p = 0.001). Diabetic patients with leukocyturia had higher IL‐8 concentration than those without it (20.9 vs. <3.1 pg/mg creatinine; p = 0.003). Weak significant correlation was found between urinary IL‐8 and hemoglobin A1c (HbA1c) (r = 0.4; p = 0.002). The sensitivity and specificity of leukocyturia were 50 and 89.9% in the whole population and those of IL‐8 were 74.1 and 67.5%, respectively. In diabetic patients, 36.4% of the bacteriuria were gram‐negative and 63.6% gram‐positive. Our results suggest that diabetic children with ASB mount an IL‐8 response to pathogens, which is comparable to non‐diabetic children with bacteriuria. Thus, early in the natural history of diabetes, there are no significant changes in the IL response of children with ASB, as previously reported in adults.

[Autoimmune comorbidity and microvascular complications in childhood-onset type 1 diabetes after 20 years of diabetes duration: a questionnaire study].

UNLABELLED There are no population-based data on the autoimmune morbidity and vascular complications of young adults with childhood-onset type 1 diabetes in Hungary. AIMS To assess the prevalence of these morbidities after 20 years of diabetes duration. METHOD Postal questionnaire. RESULTS 6.2% of the patients had celiac disease. Diabetes was diagnosed at a significantly earlier age in patients with diabetes and celiac disease as compared to those without celiac diasease. Thyroid autoimmunity was reported in 7.6% of cases. They were significantly older with longer duration of diabetes. Every fifth patients reported retinopathy, one sixth of patients was treated for hypertension. Neuropathy was found in 3.4% and kidney disease in 4.8% of the cases. CONCLUSIONS Apart from retinopathy and hypertension, the prevalence of microvascular complications was relatively low. Considering the limitations of questionnaire studies, laboratory screening is warranted to assess the true prevalence of comorbidities and complications.

Whole-Genome Draft Sequences of Nine Asymptomatic Escherichia coli Bacteriuria Isolates from Diabetic Patients

ABSTRACT Escherichia coli can colonize the urinary bladder without causing a disease response in the host. This asymptomatic bacteriuria (ABU) can protect against recurrent symptomatic urinary tract infection by virulent bacteria. Here, we report the whole-genome sequences of nine E. coli ABU isolates from diabetic patients.

Characterization of Asymptomatic Bacteriuria Escherichia coli Isolates in Search of Alternative Strains for Efficient Bacterial Interference against Uropathogens

Asymptomatic bacterial colonization of the urinary bladder (asymptomatic bacteriuria, ABU) can prevent bladder colonization by uropathogens and thus symptomatic urinary tract infection (UTI). Deliberate bladder colonization with Escherichia coli ABU isolate 83972 has been shown to outcompete uropathogens and prevent symptomatic UTI by bacterial interference. Many ABU isolates evolved from uropathogenic ancestors and, although attenuated, may still be able to express virulence-associated factors. Our aim was to screen for efficient and safe candidate strains that could be used as alternatives to E. coli 83972 for preventive and therapeutic bladder colonization. To identify ABU E. coli strains with minimal virulence potential but maximal interference efficiency, we compared nine ABU isolates from diabetic patients regarding their virulence- and fitness-associated phenotypes in vitro, their virulence in a murine model of sepsis and their genome content. We identified strains in competitive growth experiments, which successfully interfere with colonization of ABU isolate 83972 or uropathogenic E. coli strain 536. Six isolates were able to outcompete E. coli 83972 and two of them also outcompeted UPEC 536 during growth in urine. Superior competitiveness was not simply a result of better growth abilities in urine, but seems also to involve expression of antagonistic factors. Competitiveness in urine did not correlate with the prevalence of determinants coding for adhesins, iron uptake, toxins, and antagonistic factors. Three ABU strains (isolates 61, 106, and 123) with superior competitiveness relative to ABU model strain 83972 display low in vivo virulence in a murine sepsis model, and susceptibility to antibiotics. They belong to different phylogroups and differ in the presence of ExPEC virulence- and fitness-associated genes. Importantly, they all lack marked cytotoxic activity and exhibit a high LD50 value in the sepsis model. These strains represent promising candidates for a more detailed assessment of relevant fitness traits in urine and their suitability for therapeutic bladder colonization.

X kromoszómához kötött limfoproliferatív betegség (XLP): Az Epstein–Barr-vírus (EBV) találkozása egy ritka génhibával

Absztrakt: Az X kromoszomahoz kotott limfoproliferativ betegseg (XLP) ritka immundeficienciaval jaro szindroma, melyet az SH2D1A gen mutacioja okoz. A betegseget az Epstein–Barr-virusfertőzes aktiv...

Case 3: A neonate with an abdominal mass.

A male neonate was born at 39 wk gestation by vaginal delivery after 16 h of ruptured membranes. His birthweight was 3200 g, and Apgar scores were 9 and 10 at 1 and 5 min, respectively. Findings of the first physical examination revealed no abnormalities. The vaginal culture of the mother was positive for Candida sp. Because of the maternal history and the 16 h of ruptured membranes, a blood sample was drawn from the newborn and marginally elevated C-reactive protein (15.3 mg/l; reference range B/10 mg/l), elevated indirect bilirubin level (15.6 mg/dl, direct fraction 0.58 mg/dl) and normal WBC count (9.8 /10/mm) were found. Ampicillin and phototherapy were therefore initiated. On ‘‘routine’’ ultrasound (US) screening, bilateral adrenal haemorrhage was observed, which was supported by an elevated D-dimer level (2086 mg/l; reference range B/500 mg/l). Despite the ampicillin treatment, CRP elevated further (54 mg/l) and leukocytosis (17.3 /10/mm) also appeared. Antibiotic therapy was therefore changed to cefuroxime. Cultures of blood, cerebrospinal fluid, throat, urine and stool were negative. The baby had no fever and tolerated oral feeding well. Physical examination revealed a transiently palpable abdominal mass in the subcostal region on the right side. Because the serum CRP level was invariably elevated (64 mg/l), the antimicrobial therapy was modified, and a combination of ampicillin, cefotaxime and gentamycin was started. This regime was applied for an 8-d period. However, the size of the right adrenal mass increased further (51 /34 /35 mm), but it had been absorbed on the left side. On the 18th day of life, the baby was transferred to our NICU. US showed a central hyperreflective zone surrounded by an 8 12-mm-thick hypoechogenic area. Blood flow was not observed in the mass. In the 3rd week of life, the antibiotic treatment was terminated. The baby was continuously afebrile and had normal weight gain, although infection markers remained elevated (CRP 112 mg/l, ESR 180 mm/h, WBC 12 /10/mm with 56% neutrophils, 38% lymphocytes and 6% monocytes). Repeated measurements of urinary vanillylmandelic acid (VMA) showed normal levels; however, consequently elevated neuron-specific enolase (NSE) values (26, 30 and 29.6 mg/l; normal value B/12.5 mg/l) were detected. Abdominal CT scan demonstrated a large homogenic mass on the upper part of the right kidney, having a 2 3-mm-thick capsule separating it from the liver and the kidney (Figure 1). The right suprarenal gland was dislocated medially by this mass. After injection contrast medium, the picture was not changed. Because of the possibility of anaerobic infection on the basis of elevated infectious markers, clindamycin therapy was initiated. At this point, the baby was pale and his haemoglobin level had decreased to 7.4 g/dl (haematocrit of 22%), so a blood transfusion was given. The size and homogeneity of the mass did not change during the clindamycin treatment. At 6 wk of age, an operation was carried out to reveal the diagnosis.