A common complication of prosthetic heart valves is thrombosis. Although the incidence of prosthetic valve thrombosis (PVT) in the tricuspid position is high, there are not enough data on the management of it, in contrast to left-sided PVT. Here, we describe three cases of tricuspid PVT with three different management approaches: thrombolytic therapy; close observation with oral anticoagulants; and surgery. The first case was a woman who suffered from recurrent PVT, for which we successfully used Tenecteplase for second and third episodes. We employed Tenecteplase in this case for the first time in the therapy of tricuspid PVT. The second case had fixed leaflets in open position while being symptomless. At six months' follow-up, with the patient having taken oral anticoagulants, the motion of the leaflets was restricted and she was symptomfree. The last case was a woman who had a large thrombus in the right atrium immediately after mitral and tricuspid valvular replacement. The patient underwent re-replacement surgery and a new biological valve was implanted in the tricuspid position. Also, we review the literature on the pathology, signs and symptoms, diagnosis, and management of tricuspid PVT.

Purpose:

To evaluate the spectrum of organisms causing endophthalmitis and their resistance pattern to standard antimicrobial agents.

Materials and Methods:

Medical records of culture positive eyes treated at Rassoul Akram Hospital for endophthalmitis during the past 5 years were reviewed. Specimens were obtained during pars plana vitrectomy or vitreous tap.

Results:

Sixty-five isolates including 36 (55.4%) gram-positive organisms, 28 gram-negative organisms (43.1%), and 1 (1.5%) fungus were studied. The most common organism identified was Coagulase-negative staphylococcus in 16 eyes (24.6%). Among the antibiotics available for intravitreal injection, the least antibiotic resistance was for vancomycin in gram-positive organisms and amikacin and ceftazidime in gram-negative isolates.

Conclusions:

Gram-positive isolates were the most prevalent organisms; however, a high isolation rate for gram-negative organisms was obtained. Considering that no single antibiotic provides coverage for all of the organisms, a combination therapy using vancomycin/amikacin or vancomycin/ceftazidime seems to be useful as the initial empiric treatment of suspected bacterial endophthalmitis.

Objective To examine reliability and validity data for the Family Interaction Macro-coding System (FIMS) with adolescents with spina bifida (SB), adolescents with type 1 diabetes mellitus (T1DM), and healthy adolescents and their families. Methods Sixty-eight families of children with SB, 58 families of adolescents with T1DM, and 68 families in a healthy comparison group completed family interaction tasks and self-report questionnaires. Trained coders rated family interactions using the FIMS. Results Acceptable interrater and scale reliabilities were obtained for FIMS items and subscales. Observed FIMS parental acceptance, parental behavioral control, parental psychological control, family cohesion, and family conflict scores demonstrated convergent validity with conceptually similar self-report measures. Conclusions Preliminary evidence supports the use of the FIMS with families of youths with SB and T1DM and healthy youths. Future research on overall family functioning may be enhanced by use of the FIMS.

OBJECTIVE

We evaluated the prevalence of endothelial dysfunction as measured by flow-mediated dilatation (FMD) of the brachial artery and carotid intima-media thickness (c-IMT) in relationship to vascular inflammatory biomarkers in preadolescent children with type 1 diabetes.

RESEARCH DESIGN AND METHODS

We studied 21 type 1 diabetic children (aged 8.3 ± 0.3 years with diabetes duration of 4.3 ± 0.4 years) and 15 group-matched healthy siblings (aged 7.6 ± 0.3 years). Fasting plasma glucose (FPG), lipid profile, HbA1c, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, homocysteine, and erythrocyte (red blood cell [RBC]) folate were evaluated in all subjects. Each subject underwent c-IMT and brachial artery FMD percentage (FMD%) measurements using high-resolution vascular ultrasound.

RESULTS

Type 1 diabetic children had higher FPG (173.4 ± 7.9 mg/dL vs. 81.40 ± 1.7 mg/dL; P < 0.0001), HbA1c (8.0 ± 0.2% vs. 5.0 ± 0.1%; P < 0.0001), and hs-CRP (1.8 ± 0.3 vs. 0.70 ± 0.2; P = 0.017) than control children without significant differences in BMI, homocysteine, and fibrinogen levels; RBC folate content; and c-IMT between the groups. Children with type 1 diabetes had lower FMD% than control children (7.1 ± 0.8% vs. 9.8 ± 1.1%; P = 0.04), whereas c-IMT did not differ between groups.

CONCLUSIONS

Preadolescent children with type 1 diabetes and mean diabetes duration of 4 years displayed evidence of low-intensity vascular inflammation and attenuated FMD measurements. These data suggest that endothelial dysfunction and systemic inflammation, known harbingers of future cardiovascular risk, are present even in preadolescent children.

Phytoremediation refers to the use of plants for extraction and detoxification of pollutants, providing a new and powerful weapon against a polluted environment. In some plants, such as Thlaspi spp, heavy metal ATPases are involved in overall metal ion homeostasis and hyperaccumulation. P1B-ATPases pump a wide range of cations, especially heavy metals, across membranes against their electrochemical gradients. Determination of the protein characteristics of P1B-ATPases in hyperaccumulator plants provides a new opportuntity for engineering of phytoremediating plants. In this study, using diverse weighting and modeling approaches, 2644 protein characteristics of primary, secondary, and tertiary structures of P1B-ATPases in hyperaccumulator and nonhyperaccumulator plants were extracted and compared to identify differences between proteins in hyperaccumulator and nonhyperaccumulator pumps. Although the protein characteristics were variable in their weighting, tree and rule induction models; glycine count, frequency of glutamine-valine, and valine-phenylalanine count were the most important attributes highlighted by 10, five, and four models, respectively. In addition, a precise model was built to discriminate P1B-ATPases in different organisms based on their structural protein features. Moreover, reliable models for prediction of the hyperaccumulating activity of unknown P1B-ATPase pumps were developed. Uncovering important structural features of hyperaccumulator pumps in this study has provided the knowledge required for future modification and engineering of these pumps by techniques such as site-directed mutagenesis.

Objective

Sickle cell disease (SCD) is a common hereditary disease in Iran. In developed countries, newborn screening programs have been established to ensure early diagnosis, but in most developing countries, screening is not performed and the diagnosis is often delayed. The aim of the present work was to investigate the clinical presentation of SCD in Iran and comparison of its hematologic indices with normal children.

Methods

The study included 44 pediatric patients (26 boys and 18 girls) with sickle cell anemia (SS), 27 sickle /β°-thalassemia (Sβ°), and 21 sickle /β+-thalassemia (Sβ+). Fifty seven healthy individuals matched with the patients were randomly selected as controls.

Findings

Mean age at diagnosis in SS group was 4.3 years. At the time of diagnosis all patients were anemic, 89% complained of painful crises. Hemoglobin(Hb) concentration, red blood cell (RBC) count and Hb×RBC product in SS group was significantly lower than in control group (P<0.001), mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) showed no significant differences. Hb×RBC product below 45 and MCH/RBC above 7 have the best sensitivity and specificity for differenting SS group and the control normal group (91 and 98% for Hb×RBC and 89 and 100% for MCH/RBC respectively). Mean age at diagnosis in Sβ+ group was higher than in SS and Sβ° groups (7.45 year vs 4.26 and 4.25 year) (P<0.001). In addition, Sβ° and Sβ+ groups had significantly lower MCV, MCH, and Hb×RBC indices compared with control group.

Conclusion

We suggest that in an anemic patient with history of pain crises, normochrome normocytic anemia, Hb×RBC <45 and MCH/RBC ≥7, SCD should be considered and the patient evaluated accordingly to confirm the diagnosis.

Introduction

Several studies have confirmed the increasing rate of type 1 diabetes mellitus (T1DM) in children and the link with increasing BMI at diagnosis termed the ‘accelerator hypothesis’. Our objective was to assess whether changing incidence of type 1 diabetes in a group of children and adolescent from the Midwest United States was associated with changes in BMI.

Methods

Data from 1618 (52.1% M/47.9% F) newly-diagnosed children and adolescents (<19 years) with T1DM, admitted to Children's Hospital of Wisconsin (CHW) between January 1995 and December 2004, was analyzed in relationship to body mass index (BMI) standard deviation score (SDS).

Results

An overall, 10-year cumulative incidence of 27.92 per 100,000 (19.12 to 41.72/100,000) was observed, with an average yearly cumulative incidence of 2.39%. The increase was largest in the younger age groups, 0–4, 5–9, and 10–14 having an average yearly increase of 2.4, 2.3, and 3.0%, respectively, corresponding to a relative 10-year increase of 25.3, 33.8, and 38.0%, respectively. Age at diagnosis was inversely correlated with BMI SDS (p<0.001) and remained significant for both males and females.

Conclusions

Annual incidence of T1DM increased two-fold at CHW over the 10-year study period. The majority of the increase was observed in the youngest age groups, which also appeared to be the heaviest. This research adds to the growing literature supporting the hypothesis that excess weight gain during childhood may be a risk factor for early manifestation of T1DM.

Background

Type 1 diabetes (T1D) is a T-cell mediated autoimmune disease targeting the insulin-producing pancreatic β cells. Naturally occurring FOXP3+CD4+CD25high regulatory T cells (Tregs) play an important role in dominant tolerance, suppressing autoreactive CD4+ effector T cell activity. Previously, in both recent-onset T1D patients and β cell antibody-positive at-risk individuals, we observed increased apoptosis and decreased function of polyclonal Tregs in the periphery. Our objective here was to elucidate the genes and signaling pathways triggering apoptosis in Tregs from T1D subjects.

Principal Findings

Gene expression profiles of unstimulated Tregs from recent-onset T1D (n = 12) and healthy control subjects (n = 15) were generated. Statistical analysis was performed using a Bayesian approach that is highly efficient in determining differentially expressed genes with low number of replicate samples in each of the two phenotypic groups. Microarray analysis showed that several cytokine/chemokine receptor genes, HLA genes, GIMAP family genes and cell adhesion genes were downregulated in Tregs from T1D subjects, relative to control subjects. Several downstream target genes of the AKT and p53 pathways were also upregulated in T1D subjects, relative to controls. Further, expression signatures and increased apoptosis in Tregs from T1D subjects partially mirrored the response of healthy Tregs under conditions of IL-2 deprivation. CD4+ effector T-cells from T1D subjects showed a marked reduction in IL-2 secretion. This could indicate that prior to and during the onset of disease, Tregs in T1D may be caught up in a relatively deficient cytokine milieu.

Conclusions

In summary, expression signatures in Tregs from T1D subjects reflect a cellular response that leads to increased sensitivity to apoptosis, partially due to cytokine deprivation. Further characterization of these signaling cascades should enable the detection of genes that can be targeted for restoring Treg function in subjects predisposed to T1D.

Scorpion envenomations are a public health problem in many countries. Scorpions are second only to snakes in causing human fatalities from envenomation. Species of scorpions capable of inflicting fatal stings are living in North and South Africa, the Middle East, India, America, Trinidad, and Tobago. Hemiscorpius lepturus (from the Hemiscorpiidae family) is the most medically important scorpion in Iran which accounts for 92% of all hospitalized scorpion sting cases. The venom from H. lepturus is primarily a cytotoxic agent and has hemolytic, nephrotoxic, and to some extent, hepatotoxic activities. We found a combination of microangiopatic hemolytic anemia, thrombocytopenia, and acute renal failure in a seven year-old female child who was referred to us with a 12 h history of bloody urine following a H. lepturus sting. Her blood smear showed fragmented erythrocytes and burr cells, leading us to a diagnosis of hemolytic uremic syndrome (HUS). This report highlights the importance of acceptable prophylaxis and therapeutic protocols for HUS in these patients.

Background

In experimental models, Type 1 diabetes T1D can be prevented by adoptive transfer of CD4+CD25+ FoxP3+ suppressor or regulatory T cells. Recent studies have found a suppression defect of CD4+CD25+high T cells in human disease. In this study we measure apoptosis of CD4+CD25+high T cells to see if it could contribute to reduced suppressive activity of these cells.

Methods and Findings

T-cell apoptosis was evaluated in children and adolescent 35 females/40 males subjects comprising recent-onset and long-standing T1D subjects and their first-degree relatives, who are at variable risk to develop T1D. YOPRO1/7AAD and intracellular staining of the active form of caspase 3 were used to evaluate apoptosis. Isolated CD4+CD25+high and CD4+CD25− T cells were co-cultured in a suppression assay to assess the function of the former cells. We found that recent-onset T1D subjects show increased apoptosis of CD4+CD25+high T cells when compared to both control and long-standing T1D subjects p<0.0001 for both groups. Subjects at high risk for developing T1D 2–3Ab+ve show a similar trend p<0.02 and p<0.01, respectively. On the contrary, in long-standing T1D and T2D subjects, CD4+CD25+high T cell apoptosis is at the same level as in control subjects p = NS. Simultaneous intracellular staining of the active form of caspase 3 and FoxP3 confirmed recent-onset FoxP3+ve CD4+CD25+high T cells committed to apoptosis at a higher percentage 15.3±2.2 compared to FoxP3+ve CD4+CD25+high T cells in control subjects 6.1±1.7 p<0.002. Compared to control subjects, both recent-onset T1D and high at-risk subjects had significantly decreased function of CD4+CD25+high T cells p = 0.0007 and p = 0.007, respectively.

Conclusions

There is a higher level of ongoing apoptosis in CD4+CD25+high T cells in recent-onset T1D subjects and in subjects at high risk for the disease. This high level of CD4+CD25+high T-cell apoptosis could be a contributing factor to markedly decreased suppressive potential of these cells in recent-onset T1D subjects.

Background: Growth impairment during childhood and adolescence is a common problem faced by patients with an early onset of Crohn's disease.

Aims: To establish how the final adult height is affected in patients with early onset of symptoms of Crohn's disease.

Methods: Information on height, parental height, and disease history was obtained from 135 patients with Crohn's disease who reached their adult height (men 22–40 years, women 18–40 years) using a questionnaire and by outpatient measurement of height where possible. Subsequently, adult heights were expressed as standard deviation scores, with and without correction for the expected target height.

Results: Patients with onset of disease before puberty were shorter compared with patients with onset in adulthood (p<0.01). This difference was not statistically significant when adult heights were corrected for parental height. Also, height standard deviation scores for those patients with onset of disease before puberty were significantly lower than those with onset of disease during puberty (p<0.05) but after correction for parental height the difference was not significant. The site of disease had no influence on adult height. Patients who had used corticosteroids during puberty were significantly shorter than patients who had not (p=0.005). This was also true when corrected for target height (p=0.007).

Conclusions: Although there was a trend indicating a deficit in adult height in patients with an early onset of Crohn's disease, once adjustment was made for parental height, this difference was not significant. Use of corticosteroids in puberty resulted in lower adult height.