Interleukin 10 (IL10) and transforming growth factor β1 (TGFβ1) gene polymorphisms in persistent IgE-mediated cow's milk allergy

OBJECTIVES:

The aim of this cross-sectional study was to evaluate whether interleukin 10 (IL10) and transforming growth factor β1 (TGFβ1) gene polymorphisms were associated with persistent IgE-mediated cow''s milk allergy in 50 Brazilian children. The diagnostic criteria were anaphylaxis triggered by cow''s milk or a positive double-blind, placebo-controlled food challenge. Tolerance was defined as the absence of a clinical response to a double-blind, placebo-controlled food challenge or cow''s milk exposure.

METHOD:

The genomic DNA of the 50 patients and 224 healthy controls (HCs) was used to investigate five IL10 gene polymorphisms (-3575A/T, -2849A/G, -2763A/C, -1082G/A, -592C/A) and one TGFβ1 polymorphism (-509C/T).

RESULTS:

Among the five IL10 polymorphisms analyzed, homozygosis for the G allele at the -1082 position was significantly higher in the patients compared with the healthy controls (p = 0.027) and in the persistent cow''s milk allergy group compared with the healthy controls (p = 0.001).

CONCLUSIONS:

Homozygosis for the G allele at the IL10 -1082G/A polymorphism is associated with the persistent form of cow''s milk allergy.     

The natural history of cow's milk allergy in north-eastern Poland

PurposeThe rate of cow's milk allergy diminishes with age. There is not enough information concerning geographical trends in persistent cow's milk allergy in children. The objective of the study was to evaluate the prevalence of persistent cow's milk allergy in children previously diagnosed with IgE-mediated cow's milk allergy (CMA).Material/MethodsDiagnosis of cow's milk allergy was established by a medical history of symptoms associated with exposure to cow's milk, positive skin prick tests with cow's milk, the presence of milk-specific IgE, and by a positive double- or single-blind placebo-controlled food challenge with milk confirmed by a positive open-controlled milk challenge. A second oral challenge was performed after at least one year of a milk-free diet and children with a positive oral milk re-challenge were diagnosed as having a persistent CMA.ResultsTwo hundred ninety-one children, 2–14 years of age (mean 5.30±3.16 years, 95% CI, 5.02-5.62 years) completed the study. Persistent CMA was diagnosed in 79 patients (27.1%). Two hundred twelve children (72.9%) outgrew their allergy to cow's milk at a mean age of 5 years after an average time of 16.4±0.8 months on an elimination diet. Eighty percent of children below 3 years of age became milk tolerant. Milk-specific IgE (p=0.018) and history of paternal bronchial asthma and/or rhinitis (p=0.020) were associated with persistence of cow's milk allergy in regression analysis.ConclusionsAn age above 3 years, as well as features of atopy, individual and familial, may be associated with a risk of delayed tolerance to milk in children.     

In Vitro Induction of Allergen-Specific Interleukin-10-Producing Regulatory B Cell Responses by Interferon-γ in Non-Immunoglobulin E-Mediated Milk Allergy

Purpose

Specific oral immunotherapy (SOIT) using interferon-γ (IFN-γ) has been successful as a food allergy treatment. Interleukin-10 (IL-10)-producing regulatory B cells (Br1s) play a role in immune tolerance to food allergens. In addition, IFN-γ shows tolerogenic effects on allergen-induced Br1 responses.

Methods

Eleven patients that were allergic to cow''s milk and 12 milk-tolerant subjects were selected by double-blind placebo-controlled food challenge (DBPCFC) and clinical characteristics. The immunomodulatory effects of IFN-γ on allergen-specific Br1 responses were evaluated in 6 milk allergy patients and 8 milk-tolerant subjects. Peripheral blood mononuclear cells (PBMCs) from subjects were stimulated with casein and/or IFN-γ and analyzed by flow cytometry.

Results

IFN-γ had no effect on total cell counts or the proportion of Br1 cells in PBMCs. IFN-γ stimulation did not change total Br1 cell counts or the percentage of Br1s among CD5(+) B cells in the milk allergy or the milk-tolerant groups. In the milk allergy group, Br1 counts were not different between the control and the casein stimulation but significantly increased in the IFN-γ + casein stimulated cells, and the Br1 fractions were decreased after casein stimulation and recovered in the addition of IFN-γ for stimulation. In the milk-tolerant group, Br1 counts increased in the casein stimulated cells and in the IFN-γ + casein stimulated cells, but the increase was significantly less when IFN-γ was added, and the Br1 fractions were increased after casein stimulation and IFN-γ + casein stimulation, that was not significant when IFN-γ was added.

Conclusions

IFN-γ-induced allergen-specific Br1 responses in the PBMCs of milk allergy patients play a role in milk allergen-specific tolerance induction in vitro. Further investigations into the molecular immunological mechanisms underlying the induction of allergen-specific Br1 responses are needed.     

Prevalence of Immediate-Type Food Allergy in Early Childhood in Seoul

Purpose

There are scanty epidemiologic data on the prevalence of food allergy (FA) among preschool children in Asia. We performed this study to determine the prevalence and causative foods of immediate-type FA in early childhood in Korea.

Methods

A questionnaire-based, cross-sectional study was performed between September and October 2011. Children aged 0-6 years were recruited from 301 public child care centers in Seoul. Parents were asked to complete a questionnaire on FA. Children with FA were classified into "perceived FA, ever," "immediate-type FA, ever," and "immediate-type FA, current" according to the algorithm.

Results

A total of 16,749 children were included in this study. The prevalence of "perceived FA, ever," "immediate-type FA, ever," and "immediate-type FA, current" was 15.1%, 7.0%, and 3.7%, respectively. "Immediate-type FA, current" was reported by 182 (4.9%) out of 3,738 children aged ≤2 years, 262 (3.4%) of 7,648 children aged 3-4 years, and 177 (3.3%) of 5,363 children aged 5-6 years. Hen''s egg (126/621) was the most frequent cause as the individual food item, followed by cow''s milk (82/621) and peanut (58/621). Among the food groups, fruits (114/621), tree nuts (90/621) and crustaceans (85/621) were the most common offending foods. The three leading causes of food-induced anaphylaxis were hen''s egg (22/47), cow''s milk (15/47), and peanut (14/47).

Conclusions

The prevalence of immediate-type FA in early childhood is 3.7%, and is higher in younger children. The most common offending foods differed with age.     

Fetuin-A levels in obesity: differences in relation to metabolic syndrome and correlation with clinical and laboratory variables

Introduction

Fetuin-A is an important player in the enhancement of insulin resistance. There are very limited data available concerning the relationships between fetuin-A, weight status and features of the metabolic syndrome (Met S) in obese Egyptian subjects, and especially in children. The aim of the study was to evaluate fetuin-A serum level in subjects with obesity and its possible association with other laboratory and clinical variables.

Material and methods

A total of 140 obese subjects and 50 controls aged 10-40 years were recruited. Demographic, anthropometric and biochemical features were collected according to a standard protocol. Serum fetuin-A levels were measured using ELISA and the modified Third Report of the National Cholesterol Education Program (NCEP-ATP III) criteria were adopted to diagnose Met S.

Results

A higher level of serum fetuin-A was detected in obese subjects. Met S cases were also significantly associated with higher serum fetuin-A. Fetuin-A correlated significantly with BMI (r = 0.437), systolic (r = 0.228) and diastolic blood pressure (r = 0.295), waist circumference (r = 0.332), insulin resistance calculated by the homeostasis model (HOMA-IR) (r = 0.295) and high-density lipoprotein (HDL) (r = 0.362).

Conclusions

Fetuin-A levels were higher in adults and children with obesity and Met S. They were related to insulin resistance and to features of the Met S in cross-sectional analyses. Our study demonstrates a novel association between human fetuin-A and the Met S among obese subject. Therefore, fetuin-A might be a new promising link between obesity and its comorbidities.     

GABA-A receptor genes do not play a role in genetics of Lesch's typology in Caucasian subjects

Introduction

Lesch''s typology differentiates alcoholics into different treatment response subgroups. The effects of ethanol are mediated, to an important extent, via the GABA-ergic system.

Material and methods

We have evaluated the linkage disequilibrium patterns and haplotype frequencies of GABRG1 and GABRA2 genes in 133 alcoholics divided according to Lesch''s typology and in 145 matched controls.

Results

Besides several relationships at a threshold of statistical significance, we found no significant differences in the haplotype distribution of these genes between alcoholics and controls.

Conclusions

Lesch''s typology may not be related with the genotype of alcoholics – at least in terms of genes with an established role in the development of dependency.     

Impact of dietary regimen on the duration of cow's milk allergy: a random allocation study

Background The impact of diet on cow's milk allergy (CMA) duration and whether exposure to residual amounts of cow's milk protein influences the onset of tolerance are unknown. Objective To prospectively assess the dietary factors influencing disease duration in a randomized cohort. Methods We randomly switched the formula of symptomatic patients from the Milan Cow's Milk Allergy Cohort to one of three treatment groups according to the quarterly rotation of rice hydrolysate formula, extensively hydrolysed cow's milk formula and soy‐based formula. In this intention‐to‐treat, randomized analysis, a hazard ratio (HR) estimation model was used to analyse dietary impact on disease duration. Results Seventy‐two children aged a mean of 14.1±8.6 months at diagnosis were followed up for a median of 26 months. Fifty‐one reached tolerance at a mean of 34.1±15.2 months. The mean duration of disease was 40.2±4.8 months with milk hydrolysate, 24.3±3.6 months with rice and 24.3±2.6 months with soy. Dietary choice independently predicted shorter duration of disease [adjusted HRs 3.09 (P=0.007) for rice, 2.54 (P=0.02) for soy, both against milk hydrolysate]. In 50 children not co‐sensitized to soy, diet choice impacted the duration of disease more strongly [adjusted HRs 8.02 (P=0.006) for rice, 6.53 (P=0.015) for soy, both against milk hydrolysate]. Discussion Patients not exposed to cow's milk protein residue achieve cow's milk tolerance earlier than patients who follow an extensively hydrolysed cow's milk diet. This may be due to residual antigenicity in hydrolysed milks. As the effect of dietary intervention is stronger in patients not sensitized to soy, we infer that when atopic disease has progressed to multiple sensitizations, the elimination of allergenic exposure may not be sufficient to reduce the duration of CMA. Cite this as: L. Terracciano, G. R. Bouygue, T. Sarratud, F. Veglia, A. Martelli and A. Fiocchi, Clinical & Experimental Allergy, 2010 (40) 637–642.     

Diagnostic Decision Points of Specific IgE Concentrations in Korean Children With Egg and Cow's Milk Allergies

Purpose

The purpose of this study was to evaluate the utility of specific IgE (sIgE) concentrations for the diagnosis of immediate-type egg and cow''s milk (CM) allergies in Korean children and to determine the optimal cutoff levels.

Methods

In this prospective study, children ≥12 months of age with suspected egg or CM allergy were enrolled. Food allergy was diagnosed by an open oral food challenge (OFC) or through the presence of a convincing history after ingestion of egg or CM. The cutoff levels of sIgE for egg white (EW) and CM were determined by analyzing the receiver operating characteristic curves.

Results

Out of 273 children, 52 (19.0%) were confirmed to have egg allergy. CM allergy was found in 52 (23.1%) of 225 children. The EW-sIgE concentration indicating a positive predictive value (PPV) of >90% was 28.1 kU/L in children <24 months of age and 22.9 kU/L in those ≥24 months of age. For CM-sIgE, the concentration of 31.4 kU/L in children <24 months of age and 10.1 kU/L in those ≥24 months of age indicated a >90% PPV. EW-sIgE levels of 3.45 kU/L presented a negative predictive value (NPV) of 93.6% in children <24 months of age, while 1.80 kU/L in those ≥24 months of age presented a NPV of 99.2%. The CM-sIgE levels of 0.59 kU/L in children <24 months of age and 0.94 kU/L in those ≥24 months of age showed NPVs of 100% and 96.9%.

Conclusions

Our results indicate that different diagnostic decision points (DDPs) of sIgE levels should be used for the diagnosis of egg or CM allergy in Korean children. The data also suggest that DDPs with high PPV and high NPV are useful for determining whether OFC is required in children with suspected egg or CM allergy.     

Screening for hen's egg and chicken meat specific IgE antibodies in Saudi patients with allergic disorders

Background

Allergy to hen''s egg and meat contributes significantly to the manifestations of food allergy all over the world.

Objectives

This study was performed to assess the presence of hen''s egg and meat specific IgE antibodies among patients investigated for various allergic disorders.

Methods

This is a retrospective study performed at King Khalid University Hosptial, Riyadh. Data from 421 patients with allergic disorders screened for food specific IgE antibodies between January 2009 and March 2011 were analyzed. Sixty (14.25%) patients including 42 males and 18 females with the mean age (sd) of 7.5 (7.4) years were found to have specific IgE antibodies against hen''s egg and chicken meat. There were 56 (93.3%) children and 4 (6.7%) adult patients. Specific IgE antibodies were measured by radioallergosorbent test (RAST) using Pharmacia ImmunoCAP 250 analyzer.

Results

Atopic dermatitis was the most common (55%) clinical condition. Out of the total 60 patients harboring hen''s egg and chicken meat specific IgE antibodies high levels of egg white, yolk and chicken meat specific IgEs were detected in 58 (96.6%), 37 (61.6%) and 6 (10%) patients respectively. Both the egg white and yolk antibodies coexisted in 35 (58.3%) patients.

Conclusion

Sensitization against hen''s egg was higher compared to the chicken meat. Egg white sensitization higher than the egg yolk particularly in Saudi children with food related allergic disorders.     

Usefulness of nBos d 4, 5 and nBos d 8 Specific IgE Antibodies in Cow's Milk Allergic Children

Purpose

The aim of study was to assess the value of recombinants in predicting the degree of symptoms in children with and without anaphylaxis to cow''s milk.

Methods

The study included 79 children (70±40 months) referred to the Allergological Unit of the Pediatric Department between the years 2008-2012. Group A was composed of 17 children (78±49.6 months) with anaphylaxis after ingestion of milk. Group B was composed of 62 children (73.1±38.6 months) without a history of anaphylaxis, but with less severe symptoms (gastrointestinal and/or skin symptoms). All patients from Group B had a positive open challenge with cow''s milk. All patients underwent an allergic evaluation and blood samples were collected to test for IgE to recombinans of milk (nBos d 4, 5, 8).

Results

A significant difference in nBos d 8 emerged with higher levels in Group A (median [IQR]=2.80 [0.91-16.1]) than B (0.65 [0.24-1.67]; P=0.006), whereas there were no statistically significant differences for nBos d 4 and 5. The recombinants'' sum was higher in Group A than B: 8.39 [2.72-41.39] vs 3.04 [1.85-7.31] kUA/L; P=0.044. The recombinant nBos d 8 was superior to the other recombinants in identifying children at risk for anaphylaxis, with an area under the curve of 0.718 (95% CI, 0.57-0.86, P=0.006). Considering a cutoff of 1.8 kUA/L, nBos d 8 had the most favorable sensitivity and specificity ratio (sensitivity=0.65, specificity=0.77) with an odd ratio of 6.02 (95% C.I: 1.89-19.23).

Conclusions

This study suggested 2 phenotypes of allergic children, "high-anaphylaxis-risk" and "milder-risk". These types can be differentiated through measuring the level of IgE to nBos d 8.     

Combined T regulatory cell and Th2 expression profile identifies children with cow's milk allergy

The role of T regulatory cells in spontaneous recovery from cow's milk allergy (CMA) is unclear. We investigated the mRNA expression of 12 T-cell markers and the protein expression of CD4, CD25, CD127, FoxP3 after in vitro β-lactoglobulin stimulation of peripheral blood mononuclear cells from children with persisting CMA (n = 16), early recovery (n = 20) or no atopy (n = 21). Artificial neural networks with exhaustive search for all marker combinations revealed that markers FoxP3, Nfat-C2, IL-16 and GATA-3 distinguished patients with persisting CMA most accurately from other study groups. FoxP3 mRNA expression following β-lactoglobulin stimulation was highest in children with persisting CMA. Also the FoxP3 intensity in CD4⁺ CD25^highCD127^low cells was higher in children with CMA compared with non-atopic children. The expression profile of both Th2- and T regulatory cell-related genes thus reflects the clinical activity of CMA. Tolerance, in contrast, is not characterized by activation of circulating T regulatory cells.     

Expression profile of osteoprotegerin, RANK and RANKL genes in the femoral head of patients with avascular necrosis

Introduction

Femoral head avascular necrosis (AVN) is a recalcitrant disease of the hip that leads to joint destruction. Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kappa-B (RANK) and RANK ligand (RANKL) regulate the balance between osteoclasts–osteoblasts. The expression of these genes affects the maturation and function of osteoblasts–osteoclasts and bone remodeling. In this study, we investigated the molecular pathways leading to AVN by studying the expression profile of OPG, RANK and RANKL genes.

Material and methods

Quantitative Real Time-PCR was performed for evaluation of OPG, RANK and RANKL expression. Analysis was based on parallel evaluation of mRNA and protein levels in normal/necrotic sites of 42 osteonecrotic femoral heads (FHs). OPG and RANKL protein levels were estimated by western blotting.

Results

The OPG mRNA levels were higher (insignificantly) in the necrotic than the normal site (p > 0.05). Although the expression of RANK and RANKL was significantly lower than OPG in both sites, RANK and RANKL mRNA levels were higher in the necrotic part than the normal (p < 0.05). Protein levels of OPG and RANKL showed no remarkable divergence.

Conclusions

Our results indicate that differential expression mechanisms for OPG, RANK and RANKL that could play an important role in the progress of bone remodeling in the necrotic area, disturbing bone homeostasis. This finding may have an effect on the resulting bone destruction and the subsequent collapse of the hip joint.     

Serum interleukin – 4 and tumor necrosis factor alpha concentrations in children with primary acid gastroesophageal reflux and acid gastroesophageal reflux secondary to cow's milk allergy

AimThe possible role of serum interleukin 4 (IL-4) and tumor necrosis factor alpha (TNF- α) in pathogenesis of the reflux symptoms in children with primary acid gastroesophageal reflux (GER) and acid GER secondary to cow's milk allergy (CMA).Material and methodsOut of 264 children, 76 (28.8%) patients with primary GER and 62 (23.5%) patients with GER secondary to CMA (pH – monitoring) serum IL-4 and TNF- α concentrations were assessed before treatment, 1 and 2 years after the initiation of the periodically administered pharmacotherapy.ResultsChildren with primary GER had mean IL-4 concentrations 0.17 ± 0.06 pg/ml before treatment, 0.08 ± 0.07 pg/ ml after 1-year and 0.07 ± 0.06 pg/ml after 2-years of treatment. The mean IL-4 concentrations were 1.07 ± 0.24, 0.5 ± 0.22 and 0.44 ± 0.19 pg/ml respectively in children with GER secondary to CMA.The mean serum TNF- α concentrations was 3.62 ± 1.30 pg/ml before treatment, 2.16 ± 1,35 pg/ ml after 1 year and 1.65 ± 1.16 pg/ml after 2 years of treatment in children with primary GER. In group with GER secondary to CMA mean serum TNF- α concentrations were 4.95 ± 1.88, 2.53 ± 0.80 and 2.02 ± 0.78 pg/ml respectively. Statistical analysis of the concentration of both cytokines showed their differentiation between them and in the study groups.ConclusionsThe highest mean serum IL-4 and TNF-α concentrations were observed in children with GER secondary to CMA and in children in control group (with cow's milk allergy and/or other food allergy diagnosed – CMA/FA) before the treatment administration.     

Atopy patch tests are useful to predict oral tolerance in children with gastrointestinal symptoms related to non‐IgE‐mediated cow's milk allergy

Atopy patch tests (APTs) have been proposed for the diagnostic approach in children with non‐IgE‐mediated cow's milk allergy and gastrointestinal symptoms. We aimed to investigate the benefit of APTs in predicting oral tolerance in these patients. We prospectively evaluated 172 subjects with a sure diagnosis of non‐IgE‐mediated CMA and gastrointestinal symptoms (97 boys, 56.4%; age, 6.37 m; range, 2–12 m). At diagnosis, 113/172 (65.7%) children had positive APTs to cow's milk proteins (CMP). After 12 months of exclusion, diet APTs were repeated immediately before OFC. APTs significantly correlated (P < 0.001) with the OFC outcome (r 0.579). Diagnostic accuracy was sensitivity of 67.95%, specificity of 88.3%, PPV of 82.81%, NPV of 76.85%, and a +LR of 5.80. APTs are a valuable tool in the follow‐up of children with non‐IgE‐mediated CMA‐related gastrointestinal symptoms by contributing in determining whether an OFC can safely be undertaken.     

Palliative Care in Parkinson's Disease: Role of Cognitive Behavior Therapy

Background:

Parkinson''s disease (PD) is a chronic, progressive, neurodegenerative disorder that leads to the classic features of akinesia (encompassing hypokinesia and bradykinesia), tremor, rigidity and postural instability. Other non-motor complications include depression, fatigue, pain, and sleep disturbances. For the management of these complications, non-pharmacological techniques, such as Cognitive-behavioral therapy (CBT) can be used. This can focus on overt behavior and underlying cognitions and train the patient in coping strategies to obtain better symptom control.

Objectives:

To review studies on CBT as palliative care in PD patients.

Materials and Methods:

A survey was conducted for all available English-language studies by means of a MEDLINE search. Keywords in the searches included Parkinson''s disease, palliative care, and cognitive behavior therapy. All articles that reported the cognitive behavior therapy and palliative care in a group of PD patients regardless of the method used by the researchers were identified and analyzed.

Result and Conclusion:

CBT has a strong evidence base for its use and has proven to be an effective treatment in management of people with chronic pain, fatigue syndrome, depression and sleep disturbances, with efficacy that lasts beyond the duration of treatment. Although PD patients suffer from these complications, there are only a few studies on administration of CBT on them. Considering its effectiveness, CBT can be used as an option for palliative care for PD patients, directed toward improving the patient''s functional status, clinical disability and quality of life. Further studies are required in this area.     

Hypothyroidism,new nodule formation and increase in nodule size in patients who have undergone hemithyroidectomy

Introduction

The current medical literature has conflicting results about factors related to hypothyroidism and nodular recurrences during follow-up of hemithyroidectomized patients. We aimed to evaluate factors that may have a role in new nodule formation, hypothyroidism, increase in thyroid lobe and increase in nodule volumes in these patients with and without Hashimoto''s thyroiditis (HT), and with and without levothyroxine (LT4) use.

Material and methods

We enrolled 140 patients from five different hospitals in Ankara and evaluated their thyroid tests, autoantibody titre results and ultrasonographic findings longitudinally between two visits with a minimum 6-month interval.

Results

In patients with HT there was no significant difference between the two visits but in patients without HT, thyroid stimulating hormone (TSH) levels and nodule volume were higher, and free T4 levels were lower in the second visit. Similarly, in patients with LT4 treatment there was no difference in TSH, free T4 levels, or lobe or nodule size between the two visits, but the patients without LT4 had free T4 levels lower in the second visit. Regression analysis revealed a relationship between first visit TSH levels and hypothyroidism during follow-up.

Conclusions

Patients who have undergone hemithyroidectomy without LT4 treatment and without HT diagnosis should be followed up more carefully for thyroid tests, new nodule formation and increase in nodule size. The TSH levels at the beginning of the follow-up may be helpful to estimate hypothyroidism in hemithyroidectomized patients.     

Predictors of bone disease in Egyptian prepubertal children with β-thalassaemia major

Introduction

Thalassaemic osteopathy is a multifactorial disorder and limited information exists about bone accrual and bone mineral density (BMD) in prepubertal thalassaemic children. The study aimed to investigate some potential genetic and biochemical bone markers as possible early predictors of BMD variations in children with β-thalassaemia major (TM) before puberty.

Material and methods

Thirt-one prepubertal children with β-TM, and 43 matched controls were subjected to BMD assessment by dual energy X-ray absorptiometry (DEXA). Vitamin D receptor (VDR) gene polymorphisms (Bsm1, Fok1) and the biochemical bone markers serum osteocalcin and propeptide I procollagen (CPIP) and urinary deoxypyridinoline (DPD) excretion were assessed.

Results

Bone mineral density was reduced in 25% of thalassaemics at the spine and 15.4% at the hip region. Significantly higher levels of urinary DPD and lower serum osteocalcin and CPIP levels were found in the studied thalassaemic children compared to controls (p < 0.001). A significant negative correlation was present between BMD in spine and hip and the patients’ age (r = −0.6367, p = 0.0002 and r = −0.616, p = 0.00079, respectively). There was a significant reduction in BMD in males compared to females. Reduced BMD was more frequent in male patients with genotypes bb and Ff but not in females. Bone mineral density was not related to the studied biochemical bone markers, mean pre-transfusion haemoglobin or serum ferritin.

Conclusions

Routine BMD screening with DEXA is proposed to be a sensitive predictor for early bone changes, particularly at the lumbar spine. DR gene polymorphisms of Bsm1 and Fok1 polymorphisms may be determinants of BMD in Egyptian prepubertal male thalassemics     

Coats' disease in Tanzania: first case report and literature review

Background

Coats'' disease is an exudative retinal detachment with vascular telangiectasis occurring mostly in male children, the age group most affected by retinoblastoma.

Objectives

Compare the differential diagnoses of Coats'' diseaseEstablish recommendation to early disease detection.

Materials and Methods

A 3-year-old female child was referred to Muhimbili National Hospital (MNH), Tanzania, in September 2011. She had presented at the peripheral hospital with gradual onset of left eye leukocoria for 1 year and pain for 2 months. B-scan showed a mass in the left eye. A clinical diagnosis of retinoblastoma was made. Left eye enucleation was performed; the patient was referred to MNH, with the enucleated specimen.

Results

Brain and orbits scan revealed no residual tumour. The globe measured 2x1.8 cm, the optic nerve stump measured 3 mm. A whitish mass filled the vitreous, with complete retinal detachment. Microscopy showed retinal gliosis, detachment with sub retinal PAS positive exudates, vacuolation and cholesterol clefts. Foreign body giant cells were present; telangiectatic thin-walled blood vessels were identified. Clinico-pathological findings were of stage 4 Coats'' disease.

Conclusion

Coats'' disease is an important differential diagnosis of retinoblastoma. Delay to detect Coats'' disease leads to vision loss which necessitates eye enucleation as was in this child.     

Can Fecal Calprotectin Level Be Used as a Markers of Inflammation in the Diagnosis and Follow-Up of Cow's Milk Protein Allergy?

Purpose

Calprotectin is a cytosolic protein with immunomodulatory, antimicrobial, and antiproliferative actions. The concentration of calprotectin increases in infection, inflammation, and malignancy. We determined if calprotectin can be used as a marker for the diagnosis and follow-up of bowel inflammation in cow''s milk protein allergy (CMPA).

Methods

In total, 32 patients newly diagnosed with CMPA were included (24 IgE-mediated, 8 non-IgE-mediated). In all subjects, a complete blood count, total IgE, cow''s milk-specific IgE, and fecal calprotectin (FC) were assessed before and after a cow''s milk protein (CMP) elimination diet was started. The results were compared with those of 39 healthy children.

Results

The mean FC value before the CMP elimination diet was 516±311 µg/g in the 32 patients with CMPA and 296±94 µg/g in the control group (P=0.011). The mean FC value after the diet in these patients was 254±169 µg/g, which was significantly different from the mean value before the CMP elimination diet (P<0.001). When we compared FC levels before the CMP elimination diet in the IgE-mediated group with the control group, we found no significant statistical difference (P=0.142). The mean FC value before the CMP elimination diet was 886±278 µg/g in the non-IgE-mediated group and 296±94 µg/g in the control group; this difference was statistically significant (P<0.001). In the IgE-mediated and non-IgE-mediated groups, FC values after CMP elimination diet were 218±90 µg/g and 359±288 µg/g, respectively, and FC values before CMP elimination diet were 392±209 µg/g and 886±278 µg/g, respectively; these differences were statistically significant (P=0.001 and P=0.025, respectively).

Conclusions

FC levels may be a useful marker for follow-up treatment and recurrence determination in CMPA.     

Etanercept Promotes Bone Formation via Suppression of Dickkopf-1 Expression in Rats with Collagen-Induced Arthritis

Background

Various clinical reports suggest etanercept (ETN) has some efficacy in bone formation in rheumatoid arthritis (RA). To examine this effect, we investigated the gene expression of cytokines relevant to osteoblast/osteoclast differentiation, and evaluated histomorphometric findings in mature rats with collagen-induced arthritis (CIA).

Methods

Total RNA was extracted from knee joints with CIA after ETN or placebo administration. Subsequently, realtime-PCR was carried out to quantify the mRNAs encoding Wnt-1, Dickkopf-1 (DKK-1), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegelin (OPG) and TNF (tumor necrosis factor)-alpha. In histomorphometric analysis, the infiltrating pannus volume and pannus surface, and the following items in contact with pannus surface were measured: osteoclast number, osteoid surface, osteoid volume and labeling surface. These were evaluated in the distal femur with CIA with or without ETN administration.

Results

TNF-alpha, RANKL and OPG mRNA expressions, linked to osteoclastogenesis, were not significantly different with or without ETN administration. ETN administration significantly increased Wnt-1 mRNA expression, the osteoblast promoter, and decreased DKK-1 mRNA expression, the Wnt signal inhibitor. In histomorphometric analysis, pannus volume, pannus surface and osteoclast number, parameters of bone destruction, were not significantly different among groups. Osteoid volume, osteoid surface and labeling surface, parameters of bone formation, increased significantly with ETN administration.

Conclusion

Our results suggest that ETN suppresses DDK-1 expression, and, as a result, Wnt expression is promoted and osteoblastogenesis becomes more active, independent of the regulation of osteoclast activity. Marked bone formation is attributed to the fact that ETN directly promotes osteoblastogenesis, not as a result of suppressing osteoclastogenesis.