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Objective To describe a novel wrist deformity in b-thalassemia major patients, and their radiographic and magnetic resonance imaging findings. Methods 30 patients with b-thalassemia major who were noticed to have ulnar deviation at wrist joint were evaluated for previous history of medications, serum ferritin levels, presence of pain and swelling at the wrist joint, and the duration of iron chelation therapy. Radiographs of wrist and limited magnetic resonance imaging (MRI) sequences were obtained in 30 and 15 patients, respectively. Results Radiographs revealed varying severity of distal ulnar shortening, distal radial slanting and presence of soft tissue distal to the ulna. MRI showed similar deformities along with abnormal marrow signal at distal ulnar ends; in 8 patients, a soft tissue distal to the distal end of ulna was noted. Conclusions Varying severity of radiological abnormalities, predominantly affecting the distal ulna, are present in children and adolescents with b-thalassemia receiving oral chelation therapy.

To evaluate pituitary volume and iron overload in beta thalassemia major, with the objective of assessing the reliability of this method in predicting hypogonadism.3T MRI was used to measure pituitary R2 and T2* in 57 beta thalassemia major patients and 30 controls. Anterior pituitary volume was evaluated by MRI planimetry. Cardiac, hepatic, and pancreatic iron overload were also assessed using MRI T2*. Mean serum ferritin was estimated by sandwich immuno-assay. Short stature was defined as height 3 rd percentile for age, and clinical hypogonadism defined as absence of secondary sexual characteristics at ages ≥ 13 y for females and ≥ 14 y for males.Short stature was present in 32 patients (56.1%). Of the 47 patients in the pubertal age group, 11(23.4%) had hypogonadism. Serum ferritin correlated positively with pituitary R2 (p = 0.004) and negatively with anterior pituitary volume (p = 0.006), whereas pituitary R2 correlated negatively with cardiac T2* (p = 0.001). Patients with hypogonadism had lower pituitary R2 (p = 0.186), T2* (p = 0.048), and anterior pituitary volumes (p = 0.012) compared to those with normal sexual maturity. Regardless of stature, no significant difference was observed between pituitary R2 (p = 0.267) and T2* (p = 0.451). Mean pituitary R2 in patients (78.99 Hz) was higher than in controls (20.8 Hz) (p = 0.0001). Anterior pituitary volume was lower in patients (264.83 mm3T MRI is a reliable method to detect pituitary iron overload and predict risk of hypogonadism in beta Thalassemia.

As “omics” have contributed to the identification of genetic susceptibility traits in cancer research, these techniques could be ultimately extrapolated with success to the field of infectious diseases. Furthermore, we are only now beginning to fully grasp the significance of the microbiota and its interactions with the mammalian immune system in defining susceptibility to infection. Molecular testing is now well integrated into the clinical microbiology laboratory and for some pathogens has revolutionized the diagnosis and management of infectious diseases. One of the early success stories for the power of molecular detection was in the diagnosis of herpes simplex virus (HSV)-associated encephalitis. In the mid-1990’s testing for HSV DNA in cerebral spinal fluid proved to be a sensitive and specific alternative to brain biopsy, the previous gold standard for establishing this diagnosis. This was shortly followed by US Food and Drug Administration approval of the first molecular microbiology test, which was used for the detection of Chlamydia trachomatis from genital specimens. These early tests relied on polymerase chain reaction (PCR), but other amplification methods, such as branched DNA and transcription-mediated amplification, also came into widespread use. Soon enough, it became a widespread clinical practice to quantify the amount of virus directly from clinical specimens. By measuring HIV-1 RNA in plasma, clinicians have been able to design personalized treatment plans and cater to specific patient needs like never before. The use of viral load testing has progressed and been applied to the management of hepatitis C virus infections, as well as cytomegalovirus, Epstein–Barr virus, and Brennan-Krohn (BK) virus infections in the bone marrow and solid organ transplant recipients.

To assess the efficacy and safety of sofosbuvir based generic Direct Acting Antivirals (DAAs) in treatment of Hepatitis C virus (HCV) in adolescents with thalassemia major (TM). In this prospective single-arm study, 18 TM adolescents with Chronic Hepatitis C received sofosbuvir based generic DAAs. Patients with genotype 1 and genotype 3 received ledipasvir and daclatasvir respectively. Two cirrhotic patients with genotype 3 also received ribavirin. The mean age of patients was 15.1 y, of which 12 had genotype 1, 5 had genotype 3 and 1 had an undetermined genotype. Six patients had cirrhosis and 1 was treatment experienced. Sixteen of 18 patients (89%; 95% confidence interval 74 to 100%) achieved sustained virological response at 3 mo post completion of treatment with DAAs. There was a significant reduction in alanine aminotransferase levels (p

There have been various cases of salmonella osteomyelitis reported in sickle cell anemia. We present a case of emphysematous osteomyelitis caused by Salmonella typhi in a 29-year-old beta thalassemia major patient. Diagnosis of emphysematous osteomyelitis was confirmed by computed tomography and magnetic resonance imaging, and culture of pus drained during surgical debridement confirmed the causative microorganism, Salmonella typhi. Antimicrobials were given according to microbiological sensitivity for a period of 8 weeks. Our patient also received hyperbaric oxygen therapy. At the end of therapy, he was afebrile and laboratory parameters normalized with a residual joint deformity which developed within 3 months.

Background There is no published data of treating hepatitis C in thalassemia major patients with any sofosbuvir based direct acting antivirals (DAAs). This study was performed to determine the efficacy and safety of these regimes using generic drugs in the thalassemia major population. Methods In this observational study, 902 patients of thalassemia major from five transfusion centres in Mumbai were screened for HCV antibody. Of the 120 positive patients, HCV RNA was detected in 50%. The first 29 patients were enrolled for evaluating the efficacy and safety of generic sofosbuvir based DAAs. Results The 29 patients’ had a mean age of 24 years with genotype 1 in 17, genotype 3 in 11patients, while 1 patient's genotype could not be classified. Six patients had compensated cirrhosis and 8 patients were treatment experienced. SVR 12 was achieved in 100% of patients. There was significant increase in PRC (packed red cell) requirements (P = 0.0003) during treatment. At 12 weeks post-treatment, PRC requirements returned to baseline with a significant fall in serum ferritin (P = 0.03). Headache, fatigue and diarrhoea were the most common side effects. The difference in side effects including anaemia between patients who received ribavirin (19/29) and those who did not receive ribavirin (10/29) was not significant. Presence of diabetes, splenectomy, high ferritin or liver or heart iron overload on MRI T2* did not affect the efficacy of treatment. Conclusion Generic DAAs are safe in thalassemia major patients with hepatitis C with efficacy of 100%. Serum ferritin falls significantly after treatment despite an increase in transfusion requirements during treatment.

To determine the association of ocular manifestations in beta-thalassemia with the patient’s age, blood transfusion requirements, average serum ferritin and dose and duration of iron chelation therapy. Sixty multi-transfused beta thalassemia patients of 12 to 18 y of age on chelation therapy were included in this cross-sectional analysis. Structural and functional evaluation of the retina was done using Optical coherence tomography (OCT) and Electroretinography (ERG), including flash ERG and Pattern ERG (PERG). Routine ophthalmic examination and B scan of the eye was also done. Flash ERG a-waves and b-waves were recorded, however only a-wave amplitude was evaluated. Pattern ERG n35, n95 and p50 waves were recorded and p50 wave amplitude was evaluated. The a-wave on flash and p50 on pattern waves represent retinal photoreceptor epithelium (RPE) photoreceptor response, which is mainly affected in beta-thalassemia. Ocular changes were detected in 38.3% and a significant correlation was noted with increase in age (p = 0.045) but not with serum ferritin, transfusion requirements or chelation therapy. Refractive errors were found in 14 cases (23%), such as myopia with astigmatism in 13 (21.7%) and only myopia in 6 subjects (10%). OCT abnormality was noted in 1 patient (1.7%) who had thinning of central retina; right eye 132 μm and left eye 146 μm (n > 200 μm). Abnormalities were noted in a-wave amplitude on flash ERG in 20% of cases, while reduced p50 amplitude on PERG was noted in 15%. A significant correlation was noted between ocular findings and increase in age, but not with serum ferritin, transfusion requirements or chelation therapy. ERG appears to be a promising tool for screening patients with beta-thalassemia and can serve as a follow-up test for evaluating retinal function.

Extramedullary hematopoiesis (EMH) is a normal response to failure of hematopoiesis at its normal site i.e., bone marrow. It is a manifestation of many congenital hemolytic anemias and marrow failure secondary to myelodysplastic syndromes. Usually, extramedullary myeloid proliferation occurs in liver, spleen and lymph nodes. However, there are many unusual sites where EMH can occur. The authors report two cases of intracranial extramedullary hematopoiesis in beta thalassemia. In one of these patients, epidural soft tissue was detected along frontal and parietal convexities causing compression of brain parenchyma leading to raised intracranial tension and sagging of brain stem, corpus callosum and herniation of cerebellar tonsils. The other case had a similar but unilateral epidural soft tissue. Expansion of diploic spaces of skull was seen in both these cases. As myeloid proliferation is slow, it presents with subtle symptoms of headache and gradually progressive lower limb weakness. A high index of clinical suspicion coupled with imaging findings is the only way to confirm the diagnosis.

Moyamoya disease is an idiopathic, nonatherosclerotic, noninflammatory, chronic progressive cerebrovascular disease characterized by bilateral stenosis or occlusion of the arteries around the circle of Willis, typically the supraclinoid internal carotid arteries, followed by extensive collateralization, which are prone to thrombosis, aneurysm, and hemorrhage. Secondary moyamoya phenomenon or moyamoya syndrome (MMS) occurs in a wide range of clinical scenarios including prothrombotic states such as sickle cell anemia, but the association with other hemoglobinopathies is less frequently observed. We describe a case of a 25-year-old female with hemoglobin E-beta thalassemia who had a rare presentation of MMS in the form of choreoathetoid movements in the left upper and lower extremities. We describe this association, primarily to emphasize thalassemia as an extremely rare but a potential etiology of MMS. Since MMS is a progressive disease, it is important to diagnose and initiate treatment to prevent worsening of the disease and recurrence of stroke.

Non-ketotic hyperglycinemia (NKH) is an uncommon metabolic disorder with an autosomal recessive inheritance due to abnormal glycine metabolism. We present the pre-therapy and post-therapy magnetic resonance imaging, biochemical and clinical features of a child with NKH with manifestation in the early neonatal period. The initial diagnosis of NKH was made on the biochemical evidence of elevated cerebrospinal fluid (CSF) glycine levels and CSF: plasma glycine ratio. Pre-therapy magnetic resonance imaging revealed thinned out corpus callosum, intracranial hemorrhages, prominent ventricular system, few cystic changes in bilateral gangliocapsular region and abnormal T2 hyperintensities in the white matter. Magnetic resonance spectroscopy did not reveal glycine peak in our case. Post-therapy, there was clinical improvement and reduction in CSF glycine levels. In the follow up scan, myelination had progressed with residual leukomalacic changes and volume loss of white matter.

To determine efficacy of Deferasirox (DFX) on total body iron and liver iron concentration (LIC) as estimated by serum ferritin (SF) and liver MRI T2.Thirty patients had baseline MRI T2 of the liver performed to determine LIC before starting DFX therapy and classified as normal6.3 milliseconds (ms), mild 6.3-2.7 ms, moderate 2.7-1.4 ms and severe iron overload1.4 ms. DFX was given 25-35 mg/kg/d. The serum ferritin (SF) level was estimated every 3 monthly. Liver iron is expressed as liver R2 = 1,000/T2. The primary end point of the study was to determine change in SF and liver MRI R2 values after 18 mo of therapy.All 30 patients had some degree of liver iron overload; 11 (36.6 %) had severe, 15 (50 %) had moderate while 4 (13.3 %) had mild overload. The pre-DFX therapy median SF of all was 3604.5 ng/mL (IQR 2357.0-5056.0) and median liver R2 was 574.71 Hz (IQR 411.3-770.8). After 18 mo, SF dropped significantly to a median of 2036.5 ng/mL (IQR 1700.0-3162.0) (p = 0.0011), while median liver R2 decreased from 574.71 to 568.18 Hz (IQR 393.4-803.2) which was not significant (p = 0.986).DFX monotherapy at the doses used decreases total body iron, but does not significantly decrease liver iron. It is well tolerated by Indian thalassemia patients, with observed side effects including rash, diarrhea, and transient albuminuria. MRI T2 (and derived R2) can serve as useful method in non invasive monitoring of LIC in thalassemia patient management.

To evaluate osteopathy in thalassemia by bone mineral densitometry (BMD) and biochemical indices. Prospective review analysis with no follow up from 2006 to 2007 of 42 regularly transfused thalassemics aged 10–25 years (27 boys, 15 girls) was done. Anthropometry, pubertal stage and symptomatology were noted. Urinary C–terminal cross–linked telopeptide of type–1 collagen (Crosslaps) by ELISA; serum 25–OH vitamin D and osteocalcin by RIA; parathyroid hormone (PTH) and ferritin by chemiluminescence and IGF–1 by Enzyme immunoassay were evaluated. Dual Energy X-ray Absorptiometry (DEXA) of lumbar spine and femur was done on Lunar prodigy system. Data was entered and analyzed using the SPSS for Windows software. Mean comparisons were done by ANOVA 1 and data was compared using Chi–square test and p value

Background Haemoglobin E (HbE)-β-thalassaemia has a very variable clinical presentation. The management of severe cases that are often transfusion dependent is similar to that of cases of β-thalassaemia major; however, this is often not possible in India because of its high cost and the lack of availability of safe blood at many places. Thus there was a need for a drug such as hydroxyurea, which is known to reduce the transfusion requirements of patients with thalassaemia intermedia. This study was undertaken to evaluate the response of Indian patients with HbE-β-thalassaemia to hydroxyurea. Materials and methods 11 patients with HbE-β-thalassaemia receiving regular transfusion plus two less frequently transfused patients were selected for hydroxyurea therapy. Clinical and haematological evaluation was performed before and after treatment for 2 years. Molecular studies included β-globin genotype, β-globin gene haplotype, Xmn I polymorphism and α-genotyping. Results Four clinically severe patients became transfusion independent (responders) after hydroxyurea therapy, four patients showed a reduction in their transfusion requirements (partial responders), and three patients were non-responders. Responders showed a statistically significant increase in Hb, mean corpuscular volume, mean cell Hb, fetal Hb and F cells with a reduction in their transfusion requirements. A reduction in serum ferritin concentration was also seen in responders and non-responders. Conclusions Genetic markers such as Xmn I polymorphism and α-gene deletions were not always beneficial for the response to hydroxyurea therapy. Thus many more markers and a larger cohort need to be studied to predict the response in these patients.

Background The clinical and hematological response to hydroxyurea was evaluated in β thalassemia patients in western India with variable clinical severity and correlated with genetic factors. Materials and methods Seventy-nine patients-[38-β thalassemia intermedia-(group I), 41-β thalassemia major-(group II)] on hydroxyurea therapy were followed-up for 20–24 months. Results Among the frequently transfused patients in group I, 58% became transfusion independent and 16% showed a 50% reduction in transfusions after therapy which correlated with a higher mean fold increase in HbF and γ mRNA expression levels. Forty-one percent of patients in group I had associated α-thalassemia and 72.7% were XmnI (+/+). β thalassemia chromosomes among the responders of group I (41%) were linked to haplotype (− + + − + + − − +) as against haplotype (+ − − − − − − − +) being more common among the non-responders. Response was not linked to the β thalassemia mutations. Thirty-two percent of group II patients showed a 50% reduction in their transfusion requirements after therapy which also correlated with a higher mean fold increase in HbF and γ mRNA expression levels. A significant decrease in serum ferritin was seen in both groups. 19% of patients could not tolerate the drug. Conclusions In group I, clinical response to hydroxyurea was better in patients with α–thalassemia, XmnI (+/+) and a higher mean fold increase in γ mRNA expression. In group II, only one-third of patients showed a partial response.

The authors report a series of seven cases of X-linked Agammaglobulinemia, diagnosed and receiving treatment at a tertiary care centre in Mumbai. The ages of the patients ranged from 15 mo to 15 y. After diagnosis at a mean age of 3 ½ y, all were advised intravenous immunoglobulin (IvIg) infusion therapy in doses of 400-600 mg/kg every 3-4 wk. They were followed up for an average duration of 9 y, throughout which the complications and overall response to immunoglobulin therapy have been observed. The clinical profiles of each of these cases were retrospectively analysed with respect to age at diagnosis, frequency and severity of infections before and after initiation of treatment, co-morbidities and response to therapy. The results demonstrate the importance of early diagnosis and its correlation with decreased complications.

Hyper IgM syndrome is a primary immunodeficiency disorder characterized by normal or raised levels of immunoglobulin (Ig) M with low or absent IgG, IgA, and IgE. Five genetic causes of Hyper IgM have been identified. CD40L is deficient on T cells in Type І Hyper IgM, leading to defective interaction between T and B lymphocytes and consequently an inability to switch from production of IgM to other classes of antibodies. This manuscript reports a patient with X linked Hyper IgM (XHIGM) syndrome caused by a novel mutation in the CD40 Ligand (CD40L) gene and a favorable outcome after bone marrow transplantation.

To evaluate changes in annual blood transfusion requirements and complications after splenectomy in patients with β-thalassemia. Forty post-splenectomy β-thalassemic patients aged 8–33 y, receiving regular blood transfusions and chelation therapy were included and non transfusion dependant patients were excluded from this retrospective cross-sectional study. Details about their surgery, transfusion requirements, and platelet levels were recorded on a standard proforma. All patients underwent a B-mode and color-coded duplex sonography of the hepatoportal system during the study period. The average ferritin level in the year prior to the study was 4432 mcg/L (range 480–12,200 mcg/L). The annual blood transfusion requirement in the first year and 5 y post splenectomy [mean ± SD (138.41 ± 90.38 ml/kg/y); (116 ± 41.44 ml/kg/y)] were significantly different from requirements before splenectomy [(mean ± SD) 294.85 ± 226 ml/kg/y; p value

Background X-linked hyper-IgM (XHIM) is a primary immunodeficiency disorder characterized by recurrent infections, low serum IgG and IgA and normal or elevated IgM. It results from mutations in the CD40 ligand (CD40L) gene. Confirmation of diagnosis with identification of underlying molecular defect is important for the initiation of appropriate therapeutic interventions, including immunoglobulin replacement, antibiotics and bone marrow transplantation. Methods To investigate the molecular basis of XHIM, we evaluated 7 patients with suspected XHIM and abnormal CD40L expression on activated CD4+ T lymphocytes. The entire coding region and intronic splice sites of the CD40L gene were sequenced from the genomic DNA of the patients. Results 7 mutations; 3 nonsense (c.172delA, c.A229T, c.C478T), 1 missense (c.A506G) and 3 splice sites [c.346 + 2(T→C), c.289-1(G→C), c.346 + 1(G→T)] were identified, out of which 5 were novel. Conclusion A wide heterogeneity in the nature of mutations has been observed in Indian XHIM patients in the present study. Identification of mutations in this rare disorder will help in genetic diagnosis in affected families which could be further useful in prenatal diagnosis.

This study was conducted to determine L-carnitine levels in regularly transfused and chelated beta thalassemia patients (n=40; mean age, 17.5+/-5.0 years). Ten age matched controls were also studied. The mean L-carnitine level in thalassemic patients was 23.71+/- 7.3 microM as compared to control 29.26+/-2.37 microM (P0.0001). Mean carnitine was significantly lower (P=0.037) in those with ferritin greater than 2000 ng/dL (22.80+/-6.97 microM) in comparison to those with ferritin less than 2000 ng/dL (30.1+/-7.77 microM). Although carnitine levels in non vegetarians was higher (26.91+/-8.4 microM) than in vegetarians (22.34+/-6.55 microM), this difference was not statistically significant (P=0.072). We conclude that L-carnitine levels were found to be lower in thalassemics as compared to age matched controls.

To the Editor : A 10-y-old girl was diagnosed with Rubinstein Taybi Syndrome (RTS) based on distinctive facial features (low hanging columella, high palate, grimacing smile, talon cusps), broad, angulated thumbs and great toes, short stature and moderate intellectual disability (Fig. 1). Her younger sister, who died at 11 mo of age due to acute myeloid leukemia, did not have clinical features of RTS. Complete sequencing of CREBBP and EP300 genes was done for the proband as previously described [1, 2]. No pathogenic mutation was noted in CREBBP gene. She was found to be heterozygous for c.1282C > T or p.P428S mutation in exon five of EP300 gene (Fig. 1). The mutation is predicted to affect the donor splicing [3]. The patient’s mother was heterozygous for the same mutation. Prenatal diagnosis was offered to the couple and the fetus did not carry this mutation, and was confirmed to be unaffected postnatally. This mutation was not identified in 100 normal unrelated individuals. Deletion/duplication analysis of CREBBP and EP300 gene was not available. Our patient had horizontal palpebral fissures as described with EP300 related RTS, compared with CREBBP related RTS, who have anti-mongoloid slant [4]. Although patients with EP300 mutation have broad thumbs or toes, radial deviation has not been reported [2] (Fig. 1). This mutation was inherited from her mother who had mild hypertelorism, broad nasal bridge, normal intelligence and hands/feet. Negri et al. reported a patient with mutation in EP300 gene (p.N1511T) that was inherited from a healthy mother. Low penetrance in EP300 related RTS may present a challenge during genetic counseling and prenatal diagnosis [2]. EP300 gene somatic mutations are reported in acute leukemia and RTS patients have an increased incidence of cancer [2, 5]. Thus, we report an Indian child with Rubinstein Taybi Syndrome with familial EP300 gene mutation.

This study reports our experience with 67 intrauterine transfusions (IUTs) carried out for 27 cases of severe Rh alloimmunization, which could be useful to other developing countries with similar situations. Most of the mothers were from sections of India other than Mumbai, their socioeconomic status was low, and they were referred during the second or third trimester. The mean gestation age at first IUT was 27 × 2.9 weeks and maternal anti-D titer ranged from 1:32 to 1:512. Ultrasonography (USG) was normal in eight cases, but showed minimal or gross ascites in 8 and 11 cases, respectively. The mean × SD hematocrit (HCT) in three groups defined by USG was 23.5 × 1.7, 15.9 × 4, and 12 × 5.9, respectively. Amniotic fluid analysis, which proved to be an important investigation, indicated IUT in eight cases having normal USG. Six cases were severely anemic (Hb deficit > 7 g/dl). By fetal cell staining, the percentage of the donor's red cells in the fetal circulation was determined. Besides Hb, blood group, di...

Preprocedure sera of thirty one neonates requiring exchange transfusion were tested for serological markers of HBV, HCV, CMV, HIV and LFT. All the babies were investigated for these parameters one week and two months after transfusion to evaluate the risk of transmission of viral infection. Serological markers for these viral infections were also studied in the mothers and donors' blood to establish the route of infection. Donors' blood used for transfusion was pretested for HBsAg, VDRL and anti-HIV. HBsAg was detected one week post exchange in one baby and two months post exchange in two babies. Exchange transfusion was implicated in two of them, where one donor had HBsAg and the other anti-HBc. Vertical transmission accounted for the remaining one. Out of these HbsAg positive cases, one showed evidence of recently acquired CMV infection. Vertical transmission of anti-HCV was observed in one case. None of the neonates, mothers and donors were positive for anti-HIV. In view of probable serious consequences of HBV and HCV infections, blood used for exchange transfusion ought to be screened for anti-HBc and anti-HCV, besides routine HBsAg, VDRL and anti-HIV screening.

Mendelian Susceptibility to Mycobacterial Disease (MSMD) is a relatively new term that describes a spectrum of inherited defects in the IL-12/23 and IFN- γ pathways that result in a selective predisposition to disease caused by poorly pathogenic mycobacteria. In contrast to previous reports of patients infected with environmental mycobacteria and BCG, this manuscript elucidates the clinical course and diagnosis of MSMD in a child harboring extensively drug resistant (XDR) Mycobacterium tuberculosis.

Clinical manifestations in children living with HIV/ AIDS differ from those in adults due to poorly developed immunity that allows greater dissemination throughout various organs. In developing countries, HIV-infected children have an increased frequency of malnutrition and common childhood infections such as ear infections, pneumonias, gastroenteritis and tuberculosis. The symptoms common to many treatable conditions, such as recurrent fever, diarrhea and generalized dermatitis, tend to be more persistent and severe and often do not respond as well to treatment. The use of Anti Retroviral Therapy (ART) has greatly increased the long term survival of perinatally infected children so that AIDS is becoming a manageable chronic illness. As the immunity is maintained, the incidence of infectious complications is declining while noninfectious complications of HIV are more frequently encountered. Regular clinical monitoring with immunological and virological monitoring and the introduction of genotypic and phenotypic resistance testing where resources are available have allowed for dramatically better clinical outcomes. However, these growing children are left facing the challenges of lifelong adherence with complex treatment regimens, compounded by complex psycho-social, mental and neuro-cognitive issues. These unique challenges must be recognized and understood in order to provide appropriate medical management.

Prevention of Mother-To-Child Transmission (PMTCT) of HIV has been at the forefront of research in the field of HIV/AIDS since the PACTG 076 proved successful in 1994. This was followed by many trials with single, dual, or triple Anti Retroviral Therapy (ART), with or without breast-feeding, with different modes of delivery. These trials aimed and promised to find a relatively simple, low-cost intervention that could virtually eliminate the risk of HIV transmission from mother to child, cutting across all geographic boundaries. However, translation of the findings from most of these research studies into successful national PMTCT programs and health policies has not been optimal. In the west, parent to child transmission of HIV has been virtually eliminated due to universal coverage, screening, planned conception wherever possible, thorough evaluation and appropriate antenatal, intranatal and postnatal interventions. In contrast, in resource limited settings where the magnitude of the problem is the greatest accounting for more than 95 % of all vertical transmissions of HIV, there is a constant struggle dealing with the birth of an infected infant every minute. It is time to make optimal choices to prevent the transmission of HIV from an infected mother to her child and virtually eliminate this largely preventable scourge in children.

To assess the efficacy of deferasirox as an iron chelator, with specific reference to reducing cardiac iron overload.Prospective, open label, single arm study between 2008-2010. SETUP: Thalassemia center at a teaching hospital.30 multitransfused Thalassemia Major (TM) patients receiving deferasirox (DFX) therapy.All patients had MRI T2*evaluation for cardiac iron load before starting DFX therapy. MRI T2* was performed on a 1.5 tesla Siemens sonata machine using thalassemia tools software and the ejection fraction measured using standard cardiac magnetic resonance sequence. Quantification of cardiac iron deposit was categorized into T2*10 ms as high cardiac risk, 10-20 ms as intermediate risk, and20 ms as low risk. We also estimated left ventricular ejection fraction (LVEF), end systolic volume (ESV) and end diastolic volume (EDV) using standard sequence. EF56 % was considered to be significant cardiac dysfunction. DFX was administered in an initial dose of 20mg/kg/day and increased to a maximum of 35mg/kg/day. Serum ferritin level was estimated in pretransfusion samples at 1-3 monthly intervals. The primary end point of the study was change in serum ferritin level and cardiac MRI T2* value after 12-18 months therapy.Of the 30 patients, cardiac iron value of20 ms was seen in 15 (50%), whereas 9 (30%; ) had 20-10 ms, and 6 (20%) had10 ms. The mean serum ferritin pre DFX therapy of all cases was 3859.8 ± 1690.70 ng/mL (1066 - 6725 ng/mL) and mean cardiac T2* was 23.8 ± 15.2 ms (6.24-69.2 ms). After 12 to 18 months of DFX therapy on a mean dose of 33 mg/kg/day, the mean serum ferritin was 2693.4 ± 1831.5 ng/mL (drop by 30.2%, P0.001) and mean cardiac T2* was 24.2 ± 12.9 ms (increase of 1.6 %, P=0.87). Percentage change in cardiac iron was greater in high risk (24.8%) and intermediate risk (33.4%) patients than low risk patients (8.4%), though these values were not statistically significant. LVEF was 62.0 (± 7.0%) before treatment and changed to 58.9 (± 4.8%) after 18 months of therapy but the values remained within normal range and this change was not significant (P=0.061). Adverse effect of DFX included diarrhea, maculopapular skin rash and transient proteinuria that necessitated temporary stoppage of medication.Deferasirox monotherapy has a good safety profile and effectively chelates total body iron. It is also a good myocardial iron chelator, more efficacious in moderate to severe cardiac iron overloaded patients.

One of the greatest successes in AIDS research to date has by far been the discovery of successful interventions that interrupt the transmission of HIV from mother to child. It is however important to note that these successes have occurred largely in countries with great resources and the least burden of perinatal transmission of HIV. In the developing world wherein currently 95% of vertical transmission of HIV occurs, it is highly condemnable that still every minute an infected infant is said to be born in spite of the fact that vertical transmission is largely preventable, mainly because translating knowledge into practice is not always possible or feasible; This has led to a continuous growing numbers of children with HIV, thereby making pediatric HIV a looming problem rapidly draining the already burdened health care system of these countries. It is the need of the hour to appropriately address the challenges to achieve zero percent transmission of HIV from an infected mother to her child thereby giving a hope for an AIDS-free new generation worldwide.

Fibrodysplasia ossificans progressiva, also known as myositis ossificans progressiva, is characterized by congenital skeletal malformations and progressive ectopic bone formation in connective tissues. The disorder presents as rapidly growing masses usually in the neck or paraspinal region with stiffness in the adjoining joints. The preosseous lesions involve the fascia, ligaments, tendons, and skeletal muscle. These lesions occasionally resolve but more often progress to form ectopic ossification. We present a boy who had a characteristic clinical presentation. Magnetic resonance (MR) imaging conducted in the preosseous stage of the lesion revealed the pathology, resulting in early therapy and resolution of the preosseous lesion without progression to ossification. To the best of our knowledge, post-therapy follow-up MR imaging in such a case has not been reported.

With the human immunodeficiency virus (HIV) epidemic showing a shift towards women and young people, the increasing seroprevalence among women will result in an increase in the mother-to-child transmission of HIV. The vast majority of HIV-positive children worldwide acquire the infection through vertical transmission. The discovery of successful interventions that interrupt this transmission has been one of the greatest successes in AIDS research. The transmission of HIV from an infected mother to her child can be reduced to less than 2 peer cent by intensive interventions in the antenatal, intranatal and postnatal periods. To achieve this low rate, primary prevention of HIV infection in parents-to-be, early identification of seropositivity in pregnant women, prevention of unwanted pregnancies, prevention of mother-to-child transmission of HIV by appropriate antiretroviral therapy, special interventions in maternal management during labour, appropriate care and follow up of the newborn, all play an important role. However, these approaches are not always possible in developing countries wherein currently 95 per cent of vertical transmission occurs. Several questions and challenges remain. These include choice, availability, affordability, duration, long-term safety of optimal antiretroviral agents to be used during pregnancy and early neonatal life and the issue of transmission via breastfeeds in situations where alternatives to breastfeeding are not available. The challenge is to find the most cost-effective and feasible intervention to achieve zero per cent transmission of HIV from an infected mother to her child.

The discovery that purified meningococcal capsular polysaccharides are immunogenic in man 1 and can be used as vaccines2 was a major advance, since previous attempts at vaccination against meningococcal disease with whole organisms or autolysates had met with only limited success. The meningococcal vaccines are composed of chemically defined antigens consisting of purified capsftlar polysaccharides derived from bacterial cell wall, each inducing immunity against a specific serogroup. These vaccines serve as a weapon against epidemics ofmeningococcal meningitis which still occurs either sporadically or unpredictably, or in some areas with devastating regularity.3 However in most countries meningococcal infection is uncommon with annual attack rates of around one case per 100,000 population, most cases occurring among the very young, the group in which vaccines are least effective. Following the Delhi epidemic in 1985, interest in meningococcal disease and its prevention has resurged in India amongst clinicians, immunologists and even the lay population.