FREQUENCY OF ANEMIA IN CHILDREN SUFFERING FROM PNEUMONIA AT A TERTIARY CARE HOSPITAL

Objective; To determine the frequency of anemia among hospitalized children suffering from pneumonia in a tertiary care hospital.  Material and Methods; Consecutive 145 children were taken in this cross-sectional study from March 2016 to February 2017 from OPD of Nishtar Hospital, Multan, Pakistan. History regarding fever, coughing and tachypnea was taken. Once registered in the study, all the relevant baseline investigations were done including blood tests and chest X-Ray. Venous blood sample (3ml) was drawn and sent to laboratory in EDTA vial for Hb level estimation to determine anemia and all the data was entered and analyzed using SPSS-20. Results; Of these 145 study cases, 75 (51.7%) were boys while 70 (48.3%) were girls. Mean age of our study cases was 5.82 ± 2.51 years (with minimum age was 2 years while maximum age was 10 years). Most of our study cases i.e. 75 (51.7%) presented with hospital acquired pneumonia while 70 (48.3%) presented with community acquired pneumonia. Majority of our study cases i.e. 92 (63.4%) were from urban areas and were having poor social background i.e. 98 (67.6%).Mean hemoglobin level of our study cases was noted to be 9.70 ± 1.89 g/dl (with minimum Hb level was 6.5 g/dl while maximum Hb level was 12.6 g/dl). Anemia was present in 91 (62.8%) of our study cases. Conclusion; Very high frequency of anemia is noted in children with pneumonia in our study. Anemia was significantly associated with female gender, hospital acquired pneumonia, mother’s educational level, increasing disease duration and poor socio-economic status. Anemia is generally neglected while treating pediatric pneumonia so pediatricians must check hemoglobin levels on routine basis among this targeted population. Keywords; Pneumonia, anemia, frequency

FREQUENCY OF RECURRENT SEIZURES IN PATIENTS SEEKING LOADING DOSE OF MGSO4 ONLY IN ECLAMPSIA

Background; Hypertensive disorders such as eclampsia is significant contributor to maternal and perinatal mortality and morbidity worldwide particularly in the developing countries. This study was done to determine the frequency of recurrent seizures in patients seeking loading dose of MgSO4 only in eclampsia. Materials & Method: Pregnant ladies (n = 114) of any parity, 15-35 years old having more than 20 weeks gestational amenorrhea from last menstrual period were included in our study. Patients admitted with eclampsia were examined for recurrent seizures. Frequency of recurrent seizures with loading dose of mgso4 was noted till 48 hours of receiving loading dose of MgSO4. However if there was a repeat fit with loading dose of MgSO4 then an additional 2 gms MgSO4 was given intravenously and shifted to maintenance regimen. Results; Mean age of our study cases was noted to be 29.75 ± 4.56 years (with minimum age of our patients was 22 years while maximum age was 35 years). Mean parity of our study cases was noted to be 2.03 ± 1.31. Majority of our study cases i.e. 64 (56.1%) had parity less than 3 and gravidity less than 4 was noted in 82 (71.9%) of our study cases. Mean gestational age of our study cases was noted to be 30.80 ± 4.90 weeks (with minimum gestational age was 22 weeks and maximum gestational age was 38 weeks). Mean body mass index (BMI) of our study cases was noted to be 24.67 ± 3.02 kg/m2 and obesity was noted in 25 (21.9%) of our study cases. Mean number of seizures (before start of therapy) was 6.46 ± 3.21 (with minimum no. of seizures was 3 while maximum no. of seizures were noted to be 15). Recurrence of seizures was noted in 11 (9.6%) of our study cases. Conclusion; Our study results have shown that recurrence of seizures was quite low with loading dose of magnesium sulphate. It is safe, effective and reliable therapy in controlling seizures in eclampsia. Provision of loading dose of MgSO4 to these patients will not only reduce painful intramuscular injections but also helpful to reduce related costs. So use of loading dose of MgSO4 regimen is recommended of our group of patients as most of our patients are poor. Keywords; Loading dose, eclampsia, recurrence of seizures

Safety of insulin tolerance test for the assessment of growth hormone deficiency in children

OBJECTIVE: To determine the safety of insulin tolerance test (ITT) for assessing growth hormone (GH) deficiency in children. METHODS: This hospital based study was conducted at the National Institute of Child Health, Karachi from 1st November 2008 till 30th October 2009. All children suspected of growth hormone deficiency, were included after excluding all other causes of short stature. Verbal informed consent was taken from the parents. Children less than 2 years of age, weighing less than 10 kg, untreated/inadequately treated hypothyroidism or Addison\u27s disease, epilepsy, having history of hypoglycaemic fits or cardiac disease were excluded. All children were subjected to the international standard protocol of ITT and their samples of growth hormone and blood sugars were drawn. Complications during the procedure like hypoglycaemia, hypothermia, loss of consciousness, fits, vomiting and failure to achieve hypoglycaemia were recorded. Insulin tolerance test was performed on a total of 168 subjects. The data was entered in SPSS version 17 for analysis. RESULTS: A total of 168 children were subjected to the ITT. Four of them were abandoned as they could not achieve hypoglycaemia despite repeating the dose of insulin. Results were analyzed on 164 children whose mean age was 10 +/- 3.5 years, There were 96 (58%) males and 68 (41%) females. Over all 79.8% children achieved hypoglycaemia. None of the subjects developed any complication (fits, loss of consciousness,) or required intravenous glucose during the test and it was completed in all children with close monitoring. The results showed that there was a significant effect of time after insulin administration on both the blood glucose level (BG) and growth hormone (GH) levels. The blood glucose level decreased rapidly after administration of insulin and was lowest 30 minutes after injection and showed an increasing trend in subsequent readings, becoming almost equal to the baseline value 120 min after injection. From the study group 111 (66%) children were diagnosed as having growth hormone deficiency, 52 (31.3%) were normal and 1 (0.6%) had growth hormone insensitivity. CONCLUSION: ITT in children was found to be a safe and reliable test but can be potentially dangerous and requires very close monitoring and supervision and should be performed in a center with experienced staff

Disorders of sex development : insights from targeted gene sequencing of a large international patient cohort

Background: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously. Results: We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46, XY DSD and 48 with 46, XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46, XY DSD. In patients with 46, XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management. Conclusions: Our massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes

Analysis of variants in <i>GATA4 </i>and<i> FOG2/ZFPM2</i> demonstrates benign contribution to 46,XY disorders of sex development

BACKGROUND: GATA-binding protein 4 (GATA4) and Friend of GATA 2 protein (FOG2, also known as ZFPM2) form a heterodimer complex that has been shown to influence transcription of genes in a number of developmental systems. Recent evidence has also shown these genes play a role in gonadal sexual differentiation in humans. Previously we identified four variants in GATA4 and an unexpectedly large number of variants in ZFPM2 in a cohort of individuals with 46,XY Differences/Disorders of Sex Development (DSD) (Eggers et al, Genome Biology, 2016; 17: 243). METHOD: Here, we review variant curation and test the functional activity of GATA4 and ZFPM2 variants. We assess variant transcriptional activity on gonadal specific promoters (Sox9 and AMH) and variant protein-protein interactions. RESULTS: Our findings support that the majority of GATA4 and ZFPM2 variants we identified are benign in their contribution to 46,XY DSD. Indeed, only one variant, in the conserved N-terminal zinc finger of GATA4, was considered pathogenic, with functional analysis confirming differences in its ability to regulate Sox9 and AMH and in protein interaction with ZFPM2. CONCLUSIONS: Our study helps define the genetic factors contributing to 46,XY DSD and suggests that the majority of variants we identified in GATA4 and ZFPM2/FOG2 are not causative

Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis.

Autosomal Recessive Osteopetrosis is a genetic disorder characterized by increased bone density due to lack of resorption by the osteoclasts. Genetic studies have widely unraveled the molecular basis of the most severe forms, while cases of intermediate severity are more difficult to characterize, probably because of a large heterogeneity. Here, we describe the use of exome sequencing in the molecular diagnosis of 2 siblings initially thought to be affected by "intermediate osteopetrosis", which identified a homozygous mutation in the CTSK gene. Prompted by this finding, we tested by Sanger sequencing 25 additional patients addressed to us for recessive osteopetrosis and found CTSK mutations in 4 of them. In retrospect, their clinical and radiographic features were found to be compatible with, but not typical for, Pycnodysostosis. We sought to identify modifier genes that might have played a role in the clinical manifestation of the disease in these patients, but our results were not informative. In conclusion, we underline the difficulties of differential diagnosis in some patients whose clinical appearance does not fit the classical malignant or benign picture and recommend that CTSK gene be included in the molecular diagnosis of high bone density conditions

Additional file 2: Figure S1. of Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort

DSD gene variants in different global regions. DSD gene variants among the international cohort of 46,XY DSD patients. For ease of analysis, countries were grouped together into regions: Asia comprises Indonesia (97), Pakistan (25), Vietnam (35), Cambodia (16), India (1), a total of 174 patients ; Europe comprises the Netherlands (38), Austria (15), Belgium (6), and Italy (2), a total of 61 patients; and AUS & NZL comprises Australia (83) and New Zealand (7), a total of 90 patients. All curated variants are shown; those which have been curated and called pathogenic, likely pathogenic, and VUS. In the cohort from Asia, 35% of the patients were found to have a diagnostic variant (pathogenic or likely pathogenic), while this was 44% for Europe and 45% for AUS/NZL. Two patients from Canada were not included in the diagram. (PPTX 158 kb

Disorders of sex development: Insights from targeted gene sequencing of a large international patient cohort

Background: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively