Fat-Soluble Antioxidant Vitamins,Iron Overload and Chronic Malnutrition in β-Thalassemia Major

Objective

To assess the antioxidant vitamins A (retinol) and E (α-tocopherol) levels, iron status and growth retardation in children with β-thalassemia major in Odisha, an eastern state of India.

Methods

Forty three children aged 1–15 y diagnosed with β-thalassemia major (28 males and 15 females) and 42 age-matched healthy controls (22 males and 20 females) were studied. β-thalassemia was detected by using Bio-rad variant assay. Measurement of blood hemoglobin (Hb), hematocrit, serum vitamins (A and E) and ferritin was carried out by standard methods.

Results

Mean hemoglobin (6.60?±?1.84 vs. 11.8?±?2.29 g/dL, p?<?0.01), serum retinol (28.0?±?17.67 vs. 54.4?±?36.56 μg/dL, p?<?0.001) and α-tocopherol (0.2?±?0.34 vs. 1.1?±?0.82 mg/dL, p?<?0.001) were significantly lower in children with thalassemia compared with control group, however, serum ferritin (storage iron) was elevated in thalassemia patients (553.7?±?176.80 vs. 57.3?±?40.73 ng/mL, p?<?0.001). Vitamin E had significantly correlated with hemoglobin and hematocrit values in the patients. Growth retardation in terms of stunting (79 % vs. 24 %, p?<?0.0001) and thinness (32.6 % vs. 9.5 %, p?<?0.05) was significantly higher in thalassemic children compared with normal children.

Conclusions

This study shows that children with β-thalas-semia major are in a state of oxidative stress of hyperfer-ritinemia with deprived antioxidant vitamins (A and E) and poor growth status suggesting a possible need for reduction in iron overload and additional antioxidant supplementation.     

Major Causes of Hospital Admission in Beta Thalassemia Major Patients in Southern Iran

Objective

Beta thalassemia major is a prevalent hereditary disease in Mediterranean region especially Iran. Early blood transfusion is necessary for most of the patients and frequent transfusion can cause various medical problems for the patients. The aim of this study was to find major causes of hospital admission in beta thalassemia major patients to reach the accurate preventive and therapeutic plans for these patients.

Methods

Four hundred twenty six patients were admitted to the Nemazee Hospital (the main University referral Hospital Center affiliated to Shiraz University of Medical Sciences in Fars Province, southern Iran) during 3 years period (January 2007 to January 2010). A questionnaire was filled containing age, gender, hemoglobin level, frequency of blood transfusions, deferoxamine injection, cause of hospital admission and hospital course.

Findings

The mean age of patients was 11.28 years. The mean serum ferritin level was 1820±749 µg/lit. Two hundred fifty five (59.75%) patients were male and 171 (40.25%) patients were female. The top five most prevalent causes of hospital admission were splenectomy (21.8%), infections (19.9%), congestive heart failure (19.0%), diabetes mellitus (13.4%), and Liver biopsy (11.5%). (P=0.0002)

Conclusion

Results of this study revealed that infections and complications due to iron overload are major causes of hospital admission in beta thalassemia major patients.     

Influence of infection on iron profile in severely malnourished children

Objective

To study the iron profile and find out an accurate diagnostic tool which reflects iron status in different types of infection in severely malnourished children aged 12 months to 71 months.

Methods

Hundred and Eight (108) children of whom 72 children were infected and 36 non infected severely malnourished children according to WHO criteria in the age group of 12–71 months were interrogated. 36 healthy control in the same age group were also interrogated.

Results

Mean serum iron, total iron binding capacity (TIBC), ferritin concentration in normal children were significantly higher (P<0.001) than non-infected severely malnourished children. On the other hand mean serum ferritin concentration was significantly higher (P<0.001) in infected group than non-infected group but still lower than normal. Mean serum TIBC concentration significantly reduced in severely malnourished children than normal children but no significant difference was observed between non-infected and infected group. Mean serum iron, and transferrin saturation were significantly reduced (P<0.05) in parasitic infestation.

Conclusion

Severely malnourished children had reduced mean serum iron profile. Parasitic infestation influenced the marked reduction of mean serum iron concentration and transferrin saturation level. Mean serum iron concentration was reduced in acute respiratory infection(ARI) and parasitic infestation than other infections. Serum ferritin concentration was elevated in all types of infection as acute phase protein but still lower than normal. So Iron, TIBC and Transferin saturation <16% constitute good evidence for iron deficiency in both infected and non-infected severely malnourished children.     

Serum Hepcidin as a Diagnostic Marker of Severe Iron Overload in Beta-thalassemia Major

Objectives

To investigate potential usefulness of serum hepcidin in the diagnosis of iron overload in children with β-thalassemia.

Methods

A study was conducted on 30 thalassemia major (TM), 30 thalassemia intermedia (TI) and 60 healthy children as controls. Serum hepcidin was measured by Human Hepcidin, ELISA Kit.

Results

β-thalassemia patients had a higher serum hepcidin compared to the controls (p < 0.001). TM group had higher hepcidin and ferritin compared to the TI group (p = 0.034; < 0.001, respectively). Among controls, hepcidin did not correlate with age (r = 0.225, p = 0.084). Among β-thalassemia patients, it correlated positively with age (r = 0.4; p = 0.001), disease duration (r = 0.5; p < 0.001), transfusion frequency (r = 0.35; p = 0.007), total number of transfusions (r = 0.4; p = 0.003), and ferritin (r = 0.3; p = 0.027). Total hemoglobin and serum ferritin were significantly related to hepcidin, which tended to increase by 0.514 ng/ml with each 1 g/dl rise in hemoglobin (p = 0.023) and by 0.002 ng/ml with each 1 ng/ml rise in serum ferritin (p = 0.002). Iron overload [serum ferritin (SF) ≥ 1500 ng/ml] was independently associated with TM (p = 0.001) and elevated serum hepcidin (p = 0.02). The overall predictability of serum hepcidin in severe iron overload was statistically significant when compared to hepcidin to serum ferritin ratio.

Conclusions

Serum hepcidin is elevated in children with β-thalassemia; but this elevation is more evident in TM patients with severe iron overload. Thus, hepcidin can be a potential marker of severe iron overload in patients with TM. Further studies are recommended to compare serum hepcidin and serum ferritin in the prediction of severe iron overload in steady state and during infection or inflammation.

     

Frequency of Sensory Neural Hearing Loss in Major Beta-Thalassemias in Southern Iran

Objective

The thalassemias are among the most common genetic disorders worldwide, occurring more frequently in the Mediterranean region. The aim of this study was to determined frequency of sensory-neural hearing loss in major ß- thalassemias transfusion dependent patients in south of Iran.

Methods

A cross sectional study on 308 cases of major beta-thalassemia patients referring to Thalassemia Center of Shiraz University of Medical Sciences between 2006–2007 years. The diagnosis of ß- thalassemia major was based on clinical history, complete blood count and hemoglobine electrophoresis. Clinical data such as serum ferritin level, deferoxamine (DFO) dose, mean daily doses of DFO (mg/kg) and audiometric variables was recorded.

Findings

Out of 308 cases, 283 (96.5%) had normal hearing and 10 (3.5%) sensorineural hearing loss. There was no statically significant difference between two groups regarding mean age, weight, age at the first blood transfusion, age at the first DFO infusion.

Conclusion

We found the lowest incidence of sensorineural hearing loss in a large population of patients suffered from major thalassemia who received DFO. We show that DFO is not ototoxic at a low dose. When considering all related literature, as a whole there has been much critical misrepresentation about DFO ototoxicity.     

Characteristic scapular and rib changes on chest radiographs of children with ADA-deficiency SCIDS in the first year of life

Background

We describe radiographic changes in the ribs and scapulae seen in the first 6 months of life in children with ADA (adenosine deaminase) deficiency severe combined immundeficiency syndrome (SCIDS). We suggest that these changes are reversible with appropriate enzyme replacement therapy.

Objective

The purpose of this study was to describe characteristic rib and scapular radiographic changes in infants with ADA-deficiency SCIDS.

Materials and methods

This was a retrospective review of chest radiographs of nine children with ADA-deficiency SCIDS performed in the first year of life by two experienced pediatric radiologists. A control cohort of unaffected children was used for comparison.

Results

All children with ADA-deficiency SCIDS manifested unusual scapular spurring and anterior rib cupping. None of the control children manifested these changes.

Conclusion

Characteristic and reversible scapular and rib changes in the correct clinical setting should suggest an early diagnosis of ADA deficiency, prompting appropriate diagnostic and therapeutic measures.     

Quality of Life (QoL) and the Factors Affecting it in Transfusion-dependent Thalassemic Children

Objectives

To evaluate the Quality of life (QoL) and the factors affecting it in transfusion-dependent thalassemic children.

Methods

Current study was conducted at Department of Pediatrics, Dr. SNMC, Jodhpur. Ninety-three transfusion-dependent thalassemic children aged between 8 and 18 y were enrolled. Quality of life was assessed using Pediatric Quality of Life (PedsQL) measurement model in thalassemic children.

Results

Mean age of children was 11.8?±?3.2 y. Lowest mean score was observed in School functioning (57.4) while in Physical functioning, Emotional functioning and Social functioning it was 73.9, 82.2 and 83.49 respectively. Mean PedsQL score was higher in 8-12 y age group as compared to 13-18 y (p?=?0.024). PedsQL score was higher in children who required transfusion once in a month (p?=?0.028) and children on combined chelation therapy as compared to children who were on injectable chelator (p?=?0.039). Health Related QoL was not affected with gender, education status, family history of thalassemia, ferritin level, splenectomy or consanguinity.

Conclusions

Factors related with low QoL in current study were higher age, increased transfusion frequency and injectable mode of chelation. In order to improve the QoL in thalassemic children appropriate programmes and interventions should be started targeting above domains.

     

MR imaging findings suggestive of posterior reversible encephalopathy syndrome in adolescents with systemic lupus erythematosus

Background

Endothelial damage, hypertension and cytotoxic medications may serve as risk factors for the posterior reversible encephalopathy syndrome (PRES) in systemic lupus erythematosus. There have been few case reports of these findings in pediatric lupus patients.

Objective

We describe clinical and neuroimaging findings in children and adolescents with lupus and a PRES diagnosis.

Materials and methods

We identified all clinically acquired brain MRIs of lupus patients at a tertiary care pediatric hospital (2002–2008). We reviewed clinical features, conventional MRI and diffusion-weighted imaging (DWI) findings of patients with gray- and white-matter changes suggestive of vasogenic edema and PRES.

Results

Six pediatric lupus patients presenting with seizures and altered mental status had MRI findings suggestive of PRES. In five children clinical and imaging changes were seen in conjunction with hypertension and active renal disease. MRI abnormalities were diffuse and involved frontal regions in five children. DWI changes reflected increased apparent diffusivity coefficient (unrestricted diffusion in all patients). Clinical and imaging changes significantly improved with antihypertensive and fluid management.

Conclusion

MRI changes suggestive of vasogenic edema and PRES may be seen in children with active lupus and hypertension. The differential diagnosis of seizures and altered mental status should include PRES in children, as it does in adults.     

Co-morbidities in hospitalized children with severe acute malnutrition

Objective

To study the co morbidities in hospitalized children with severe acute malnourishment.

Methods

104 severe acute malnourished children were included.

Results

54% had diarrhea and 27.8% had acute respiratory tract infections. Tuberculosis was diagnosed in 22% of cases (60.8% cases in children 6–12 mo old). Malaria and Measles were diagnosed in 3.8% each, and HIV infection was seen in 2.9% cases. Signs of vitamin B and vitamin A deficiency were seen in 14.4% and 5.8% cases, respectively. Malaria and HIV were not found to be major co morbid conditions.

Conclusions

Timely identification and treatment of various co-morbidities is likely to break undernutrition-disease cycle, and to decrease mortality and improve outcome.     

Aeroallergen sensitization in childhood asthmatics in Northern India

Abstract

To determine the prevalence of sensitization to common aeroallergens in asthmatic children and study the differences in characteristics of atopics and non atopics.

Design

Analysis of data from a prospective cohort study.

Setting

Pediatric Chest Clinic of tertiary care center in Northern India

Patients

Asthmatic children from 5–18 year of age.

Main outcome measures

Prevalence of sensitization to common aeroallergens.

Results

Skin prick testing (SPT) was performed on 180 children above 5 years of age, with a mean (SD) age of 111.4 (34.2) months. 100 children (55.6%) were sensitized to at least one aeroallergen, suggesting atopy; 68 (37.8%) were sensitized to more than one allergen. 36.7% children were sensitized to housefly antigen; 31.1% to rice grain dust, 18.3% to cockroach, and 7.8% to house dust mite antigens. Atopic children had significantly higher median FENO during follow up than nonatopic children (17.5 ppb vs 13 ppb, P=0.002). There was a positive correlation between age and the number of allergens that an individual was sensitized to (r= 0.21; P=0.0049).

Conclusions

More than half of asthmatic children in our cohort had sensitization to one or more aeroallergens suggesting atopy; sensitization was most commonly seen to housefly antigen and rice grain dust. Atopic children had significantly higher FENO measurements during follow up as compared to non-atopic children.     

Correlative BOLD MR imaging of stages of synovitis in a rabbit model of antigen-induced arthritis

Background

Because of the ability of blood-oxygen-level-dependent (BOLD) MRI to assess blood oxygenation changes within the microvasculature, this technique holds potential for evaluating early perisynovial changes in inflammatory arthritis.

Objective

To evaluate the feasibility of BOLD MRI to detect interval perisynovial changes in knees of rabbits with inflammatory arthritis.

Materials and methods

Rabbit knees were injected with albumin (n?=?9) or saline (n?=?6) intra-articularly, or were not injected (control knees, n?=?9). Except for two rabbits (albumin-injected, n?=?2 knees; saline-injected, n?=?2 knees) that unexpectedly died on days 7 and 21 of the experiment, respectively, all other animals were scanned with BOLD MRI on days 0, 1, 7, 14, 21 and 28 after induction of arthritis. T2*-weighted gradient-echo MRI was performed during alternate 30?s of normoxia/hyperoxia. BOLD MRI measurements were compared with clinical, laboratory and histological markers.

Results

Percentage of activated voxels was significantly greater in albumin-injected knees than in contralateral saline-injected knees (P?=?0.04). For albumin-injected knees (P?P?=?0.009), the percentage of activated BOLD voxels varied over time. A quadratic curve for on-and-off BOLD difference was delineated for albumin- and saline-injected knees over time (albumin-injected, P?=?0.047; saline-injected, P?=?0.009). A trend toward a significant difference in synovial histological scores between albumin-injected and saline-injected knees was noted only for acute scores (P?=?0.07).

Conclusion

As a proof of concept, BOLD MRI can depict perisynovial changes during progression of experimental arthritis.     

Pattern of Pediatric Dermatoses at a Referral Centre

Objective

To determine the pattern of skin disorders seen among children attending a Medical College Hospital, Bangalore

Methods

All children 18 y and below attending the Pediatric Dermatology OPD with skin diseases between the period of January 2011 and June 2011 were included in the study.

Results

A total of 1,090 new cases (boys 589; girls 501) with 1,118 dermatoses were recorded during this period. Twenty eight children had more than one dermatoses. Most of the disorders were seen between 5 and 11 y age group. The most common dermatoses was infections and infestations (32.47 %) followed by eczematous eruptions and dermatitis (20.66 %), papulosquamous and related disorders (6.08 %) and pigmentary disorders (5.81 %). Insect bite reactions and papular urticaria formed 5.1 %. Acne was seen in 5.28 % of children followed by urticaria (3.67 %), photodermatoses 2.5 % and genetic disorders (3.04 %).

Conclusions

In the present setting bacterial infections and scabies still remained the most common pediatric dermatoses followed by molluscum contagiosum and atopic dermatitis. Childhood psoriasis contributed to major part of the study among papulosquamous disorders.     

Diagnostic errors in interpretation of pediatric musculoskeletal radiographs at common injury sites

Background

Extremity pain represents one of the most common reasons for obtaining conventional radiographs in childhood. Despite the frequency of these examinations little is known about the incidence of diagnostic errors by interpreting pediatric radiologists.

Objective

The purpose of this study was to develop a standard error rate of pediatric radiologists by double-reading of extremity radiographs (elbow, wrists, knees and ankles) in children presenting with a history of trauma or pain.

Materials and methods

During a 6-month period all major extremity radiographs (excluding digits) obtained at a large pediatric referral hospital for evaluation of pain or trauma were reviewed by two senior pediatric radiologists and compared to the official interpretation. All radiographs were interpreted initially by a board-certified pediatric radiologist with a Certificate of Added Qualification (CAQ). We reviewed 3,865 radiographic series in children and young adults 2–20 years of age. We tabulated misses and overcalls. We did not assess the clinical significance of the errors.

Results

There were 61 miss errors and 44 overcalls in 1,235 abnormal cases and 2,630 normal cases, for a 1.6% miss rate and a 1.1% overcall rate. Misses and overcalls were most common in the ankle.

Conclusion

Interpretive errors by pediatric radiologists reviewing certain musculoskeletal radiographs are relatively infrequent. Diagnostic errors in the form of a miss or overcall occurred in 2.7% of the radiographs.     

Low iron storage in children with tilt positive neurally mediated syncope

Background

The mechanisms under neurally mediated syncope (NMS) are not fully understood. This study aimed to assess the level of storage iron in children with different hemodynamic patterns in head-up tilt test.

Methods

Altogether 210 children (11.31±2.49 years) with syncope or pre-syncope treated between May 2008 and September 2010 were studied prospectively. Following history taking and physical examination, their levels of hemoglobin (Hb), hematocrit (Hct) and serum ferritin were measured.

Results

In the 210 children, 162 (77.1%) had NMS and 48 (22.9%) had syncope due to other causes. In the 162 children with NMS, 98 children were subjected to positive tilt test. The level of serum ferritin was significantly lower in the 98 children with NMS (P<0.001). The comparison of levels of Hb, Hct and mean cell volume (MCV) displayed no significant difference between the two groups. Reduced iron storage (serum ferritin <25 ng/mL) was found to be more prevalent in children with NMS (63% vs. 20%, P<0.001). Prevalence of iron deficiency was also significantly higher in children with NMS than in children with syncope due to other causes (27% vs. 6%, P=0.003).

Conclusions

In head-up tilt test positive children with NMS, the level of serum ferritin should be evaluated. Low storage iron may be one of the underlying mechanisms of NMS.     

Quality Matters–Hematopoietic Stem Cell Transplantation <Emphasis Type="Italic">versus</Emphasis> Transfusion and Chelation in Thalassemia Major

Objective

To compare quality of life of children with thalassemia major who have undergone stem cell transplantation with those on regular transfusion.

Methods

The study included 40 children who underwent transplantation and 40 children and 20 adults on regular transfusion and iron chelation therapy. The quality of life assessment was done using the Pediatric Quality of Life Inventory 4.0 Generic Core Scale.

Results

The mean total summary score, psychosocial summary score and physical score was 92, 91 and 92.8, respectively in transplant group and 83, 82.7 and 83.6, respectively in children in transfusion group. The adult group on transfusion showed overall poorer scores of 74.9, 76 and 73.9, respectively. The average scores in all domains were significantly (P<0.05) lower and drop steeply in second decade in transfusion group.

Conclusion

Allogeneic stem cell transplantation improves quality of life in thalassemia major.

     

Validation of automatic bone age determination in children with congenital adrenal hyperplasia

Background

Determination of bone age is routinely used for following up substitution therapy in congenital adrenal hyperplasia (CAH) but today is a procedure with significant subjectivity.

Objective

The aim was to test the performance of automatic bone age rating by the BoneXpert software package in all radiographs of children with CAH seen at our clinic from 1975 to 2006.

Materials and methods

Eight hundred and ninety-two left-hand radiographs from 100 children aged 0 to 17 years were presented to a human rater and BoneXpert for bone age rating. Images where ratings differed by more than 1.5 years were each rerated by four human raters.

Results

Rerating was necessary in 20 images and the rerating result was closer to the BoneXpert result than to the original manual rating in 18/20 (90 %). Bone age rating precision based on the smoothness of longitudinal curves comprising a total of 327 data triplets spanning less than 1.7 years showed BoneXpert to be more precise (P<0.001).

Conclusion

BoneXpert performs reliable bone age ratings in children with CAH.     

Safety and efficacy of a drug regimen to control heart rate during 64-slice ECG-gated coronary CTA in children

Background

The adult practice for ECG-gated single-source 64-slice coronary CTA (CCTA) includes administering beta-blockers to reduce heart rate. There are limited data on this process in children.

Objective

To evaluate the safety and efficacy of a drug regimen to decrease heart rate before performing CCTA in children.

Materials & methods

IV remifentanil and esmolol infusion were chosen to decrease heart rate in 41 children (mean age 6.5 years) while they were under general anesthesia (GA) for CCTA. Drug doses, changes in heart rate and procedural complications were recorded. CCTA image quality was graded on a scale of 1 to 5. The relationships between image quality and heart rate and image quality and age were evaluated. Patient effective radiation doses were calculated.

Results

Heart rates were lowered utilizing esmolol (4 children), remifentanil (2 children) or both (35 children); 26 children received nitroglycerin for coronary vasodilation. The mean decrease in heart rate was 26%. There were no major complications. The average image-quality score was 4.4. Higher heart rates were associated with worse image quality (r?=?0.67, P?<?0.0001). Older age was associated with better image quality (r?=?0.66, P?<?0.0001). Effective radiation doses were 0.7 to 7.0 mSv.

Conclusion

Heart rate reduction for pediatric CCTA can be safely and effectively achieved while yielding high-quality images.     

Assessment of Thyroid Function in Children Aged 1-13 Years with Beta-Thalassemia Major

Objective

Hypothyroidism usually appears in the second decade of life and is thought to be associated with iron overload in patients with thalassemia major. This study aimed to evaluate thyroid dysfunctions in patients with beta-thalassemia major and to see if they appear in the earlier period of life.

Methods

Thyroid function and iron load status were evaluated in 90 children with a mean age of 7.17±3.78 years with beta-thalassemia major by measuring serum free thyroxin (FT4), serum free triiodothyronine (FT3), total thyroxin (T3), serum total triiodothyronine (T4), thyroid-stimulating hormone (TSH) and ferritin levels from serum of patients admitted to the Pediatric Department, Faculty of Medicine University of Dicle between March 2005 and July 2009. A control group formed from an age-sex matched healthy children with a mean age of 6.98±3.66 years was also included. A standard thyrotropin releasing hormone test was applied to 3 patients who had high TSH levels and were classified as subclinical primer hypothyroidism. The study was designed according to the Declaration of Helsinki and informed consent was obtained from the parents of all participants.

Findings

All thyroid parameters in patients were in the normal ranges compared with the controls except three of them which had high TSH levels. Serum ferritin level (2703±1649 ng/mL) in patients was significantly higher than in controls (81.5±15.5 ng/mL).

Conclusion

The work implies that hypothyroidism could be even seen in the first decade of life in patients with beta-thalassemia major in spite of improved hematological cares.     

Communicating hydrocephalus in systemic lupus erythematosus

Background

Central nervous system involvement is common in systemic lupus erythematosus but hydrocephalus, especially in children, is rare.

Case characteristics

6-year-old girl with systemic lupus erythematosus with nephritis, on treatment for four months prior to the presentation with features of raised intracranial pressure.

Observation

Computed tomography revealed communicating hydrocephalus without any evidence of granulomatous lesion, infarction or thrombosis, with no features of lupus flare. Ventriculoperitoneal shunting provided symptomatic relief after failed medical management.

Message

Hydrocephalus may be seen in systemic lupus erythematosus without tuberculosis or major vessel vasculitis.