Clinicopathological investigation of nutritional osteodystrophia fibrosa in a flock of young stall-fed goats.

Background: Osteodystrophia fibrosa (ODF) is a metabolic disorder affecting the skeletal system, causing progressive loss of calcified bone mass and its replacement with fibrous tissue, which may be a sequel to primary or secondary hyperparathyroidism. This report intends to document the clinicopathological findings of ODF in a flock of young goats fed primarily on a wheat bran-rich diet. Case description: In a flock of 50 stall-fed goats aged 1 to 2 years, seven were clinically presented with bilateral facial enlargement, leading to dyspnea and difficulty in prehension and mastication. Among the seven clinically affected goats, four died in 2 months. Findings/treatment and outcome: The clinical examination revealed bilateral mandibular enlargement and limb deformities. On radiography, the maxilla and mandible had decreased radiopacity. Fine needle aspiration cytology (FNAC) from the affected bones showed occasional fibroblasts and individual osteoclasts clusters. On necropsy, the enlarged mandible revealed a meaty consistency. Undecalcified histological sections of the mandible showed severe osteopenia, multiple osteoclasts, Howship's lacunae, and extensive fibroplasia. Dietary corrective measures led to the prevention of ODF in the rest of the flock. Conclusion: Excessive wheat bran feeding in stallfed goats might have led to calcium and phosphorus imbalance, resulting in nutritional secondary hyperparathyroidism and subsequent skeletal deformities. FNAC of the affected bones, gross and histological findings provide a clinicopathological diagnosis of ODF.

Duration of Caffeine for Apnea of Prematurity-A Randomized Controlled Trial.

OBJECTIVES: There is sufficient evidence to support use of caffeine therapy for apnea of prematurity, but practices vary widely when it comes to discontinuing therapy. This study was planned to compare 'recurrence of apnea of prematurity' (RAP); when 2 protocols were used to stop caffeine therapy. METHODS: Neonates delivered at 26-32 wk gestation on caffeine therapy for apnea of prematurity were randomized into 2 groups: Group 1-caffeine stopped at 7 d apnea-free period, and Group 2-continued for a prefixed period till at least 34 wk postmenstrual age (PMA). Proportion of infants in each group with RAP were analyzed. RESULTS: Each group consisted of 60 infants. Proportion of infants in each group with RAP, were not different (15% vs 13%); odds ratio (OR) 0.87; 95% confidence interval (CI) (0.31-2.43). Caffeine could be stopped earlier (33 vs 34 wk PMA); and cumulative duration of therapy was lesser (19.5 vs 33 d) when stopped at 7 d apnea-free period. Other studied outcomes were similar between the two groups. CONCLUSIONS: Mandatorily continuing caffeine therapy up to 34 wk PMA in select preterm groups does not seem to decrease risk of recurrence of apnea. Larger trials that specifically study extremely preterm infants are required to make robust recommendations on when to stop therapy. CLINICAL TRIALS REGISTRY OF INDIA NO: CTRI/2016/12/007559. http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=14195&EncHid=&modid=&compid=%27,%2714195det%27.

Exclusive Breast Milk vs. Hybrid Milk Feeding for Preterm Babies-A Randomized Controlled Trial Comparing Time to Full Feeds.

When breastmilk is insufficient to meet planned feed volumes, neonatologists need to continue parenteral nutrition (PN) or use formula. This trial conducted at a tertiary care unit in South India between August 2014 and April 2016 compared time to full feeds in preterms fed 'mother's milk alone(MM)' vs. 'hybrid feed-mother's milk supplemented with formula(HF)'. We also compared time to regain birth weights, duration of PN, feed intolerance, Necrotizing Enterocolitis stage 2 or more, all-cause mortality, Extrauterine growth restriction, Healthcare associated infections, exclusive breast milk feeding rates at discharge, Retinopathy of prematurity requiring laser therapy, abnormal neurosonogram and oxygen dependency at 28 days. Neonates between 27 and 32 weeks were randomized into MM/HF when breast milk was insufficient. HF received formula to reach targeted feed volumes. MM received more PN to meet fluid requirements. 54 babies were analyzed in MM and 58 in HF. Time to full feeds were similar-MM (14.1 ± 4 days); HF (13.5 ± 4 days), p = 0.45. Exclusive breast milk feeding rates at discharge were higher in MM when compared to HF (74% vs. 51%). Other secondary outcomes were similar between groups. When mother's milk is unavailable in sufficient quantities, preterm babies may receive hybrid feeds. (Clinical trials registry of India no. REF/2016/02/006622).

Cold-stored platelets: A product with function optimized for hemorrhage control.

Early administration of blood products following severe trauma is pivotal for establishing hemostasis and achieving successful outcomes. Platelet transfusions, in particular, provide rapid control of hemostasis and help to restore platelet dysfunction induced by trauma. In the U.S. platelets used for therapeutic purposes are stored at room temperature with a limited shelf life of 5-7 days. Issues with room temperature storage of platelets, including an increased risk of bacterial growth and a decline in platelet hemostatic function, have led to a resurgence in interest in cold-stored platelets for therapeutic transfusion. This review presents the current state of cold-stored platelets and cold-stored whole blood as treatment for actively bleeding patients. Usage of cold stored platelets in alternative areas, such as in the field of regenerative medicine, is also discussed.

Targeting PP2A and proteasome activity ameliorates features of allergic airway disease in mice.

BACKGROUND: Asthma is an allergic airway disease (AAD) caused by aberrant immune responses to allergens. Protein phosphatase-2A (PP2A) is an abundant serine/threonine phosphatase with anti-inflammatory activity. The ubiquitin proteasome system (UPS) controls many cellular processes, including the initiation of inflammatory responses by protein degradation. We assessed whether enhancing PP2A activity with fingolimod (FTY720) or 2-amino-4-(4-(heptyloxy) phenyl)-2-methylbutan-1-ol (AAL(S) ), or inhibiting proteasome activity with bortezomib (BORT), could suppress experimental AAD. METHODS: Acute AAD was induced in C57BL/6 mice by intraperitoneal sensitization with ovalbumin (OVA) in combination with intranasal (i.n) exposure to OVA. Chronic AAD was induced in mice with prolonged i.n exposure to crude house dust mite (HDM) extract. Mice were treated with vehicle, FTY720, AAL(S) , BORT or AAL(S) +BORT and hallmark features of AAD assessed. RESULTS: AAL(S) reduced the severity of acute AAD by suppressing tissue eosinophils and inflammation, mucus-secreting cell (MSC) numbers, type 2-associated cytokines (interleukin (IL)-33, thymic stromal lymphopoietin, IL-5 and IL-13), serum immunoglobulin (Ig)E and airway hyper-responsiveness (AHR). FTY720 only suppressed tissue inflammation and IgE. BORT reduced bronchoalveolar lavage fluid (BALF) and tissue eosinophils and inflammation, IL-5, IL-13 and AHR. Combined treatment with AAL(S) +BORT had complementary effects and suppressed BALF and tissue eosinophils and inflammation, MSC numbers, reduced the production of type 2 cytokines and AHR. AAL(S) , BORT and AAL(S) +BORT also reduced airway remodelling in chronic AAD. CONCLUSION: These findings highlight the potential of combination therapies that enhance PP2A and inhibit proteasome activity as novel therapeutic strategies for asthma.

A pathogenic role for tumor necrosis factor-related apoptosis-inducing ligand in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory respiratory disorder, often induced by cigarette smoke (CS) exposure. The development of effective therapies is impaired by a lack of understanding of the underlining mechanisms. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. We interrogated a mouse model of CS-induced experimental COPD and human tissues to identify a novel role for TRAIL in COPD pathogenesis. CS exposure of wild-type mice increased TRAIL and its receptor messenger RNA (mRNA) expression and protein levels, as well as the number of TRAIL(+)CD11b(+) monocytes in the lung. TRAIL and its receptor mRNA were also increased in human COPD. CS-exposed TRAIL-deficient mice had decreased pulmonary inflammation, pro-inflammatory mediators, emphysema-like alveolar enlargement, and improved lung function. TRAIL-deficient mice also developed spontaneous small airway changes with increased epithelial cell thickness and collagen deposition, independent of CS exposure. Importantly, therapeutic neutralization of TRAIL, after the establishment of early-stage experimental COPD, reduced pulmonary inflammation, emphysema-like alveolar enlargement, and small airway changes. These data provide further evidence for TRAIL being a pivotal inflammatory factor in respiratory diseases, and the first preclinical evidence to suggest that therapeutic agents that target TRAIL may be effective in COPD therapy.

Neonatal seizures: Predictors of adverse outcome.

CONTEXT: Early detection of predictors of adverse outcome will be helpful for neonatologists to plan management, follow up and rehabilitation in advance so that neurological disability can be minimised. AIMS: The purpose of this study was to determine the factors affecting the adverse outcome of neonatal seizures. SETTINGS AND DESIGN: This is a prospective study conducted in the neonatal unit of a tertiary care hospital. One hundred and eight newborns consecutively admitted with seizures were included in this study. MATERIALS AND METHODS: Data was collected regarding perinatal history and seizure and evaluated for etiology. We conducted a retrospective analysis to identify the factors associated with adverse outcome after neonatal seizures. STATISTICAL ANALYSIS USED: Chi-square test with degree of freedom = 1 was used to find the variables significantly associated with adverse outcome (P < 0.05). RESULTS: Gestational age, birth weight, Apgar score at 5 min, seizure onset <24 hrs, status epilepticus, radiological findings and EEG findings were significantly associated with outcome. CONCLUSION: Mortality and severe neurological impairment after neonatal seizure is associated with prematurity, LBW, low Apgar score at 5 min, etiologies like meningitis, sepsis, severe HIE, brain malformations, grade 3 or 4 IVH or intracranial haemorrhage, seizure onset <24 hours, presence of status epilepticus, severely abnormal radiological and EEG findings.

The newborn with seizures -- a follow-up study.

OBJECTIVE: To determine the sequelae of neonatal seizures in a cohort of newborns, recruited over a six month period. DESIGN: Prospective hospital based study. SETTING: The neonatal intensive care unit (NICU) of a tertiary care hospital. PARTICIPANTS: 135 babies were recruited of whom 10 died and 25 were lost to follow up. METHODS: The cases were followed up over four months. RESULTS: 68% of the babies followed up were normal; 32% had an abnormal neurological outcome. Seven (7%) developed post-neonatal epilepsy. Hypocalcemia was significantly associated with mortality (OR: 21.9; 95% CI: 1.2-391.2). No risk factors could be identified for post neonatal epilepsy. Presence of spike waves in the EEG was significantly related to abnormal neurological outcome (OR: 3.5; 95% C.I. 1.2-10.8). CONCLUSIONS: Majority of neonates with seizures have a normal outcome with no developmental delay or neurological deficit. Predominantly spike waves in the EEG is predictive of abnormal neurological outcome.

Callosal agenesis and Open lip Schizencephaly.

We report a case of a new born who presented with neonatal seizures; and who had coexistence of a Corpus Callosum Agenesis with a bilateral Open lip Schizencephaly and a Dandy Walker malformation. The investigations for an underlying etiology, however was futile.

BK virus nephropathy in renal transplant recipients in Kuwait: a preliminary report.

INTRODUCTION: BK virus nephropathy (BKVN) is a significant cause of graft loss among renal transplant recipients. The treatment outcomes of BKVN have been variably reported in the literature. PATIENTS AND METHODS: We prospectively investigated BKV infection and BKVN among a population of renal transplant recipients with suspected BKV infection. The 42 subjects who all had acute allograft dysfunction, were categorized in three groups: those with clinical, laboratory, and histological findings that did not suggest acute rejection, drug toxicity, or obstruction (group 1, n = 24); those with findings that suggested probable acute cellular rejection but did not respond to antirejection treatment (group 2, n = 10); and those whose renal histology suggested BKVN (group 3, n = 8). Polymerase chain reaction analysis was done to detect BKV DNA in urine and blood samples from each subject. BKV DNA was detected in 19 (45%) urine samples with 11 of these subjects (26.1% of total) having BK viremia as well. RESULTS: No evidence of BKVN was detected histologically in seven subjects with isolated BK viruria, while the others proved to be JC virus infections. Among the 11 subjects with BK viremia, eight had BKVN based on renal histology at the time of diagnosis with BKV infection, while the other three subsequently developed histological features of BKVN. BKVN developed after 5.3 +/- 2.5 (2 to 44) months after transplantation. The serum creatinine at time of BKVN diagnosis was 158.9 +/- 58 (87 to 285) micromol/L. All subjects were initially treated with a 50% reduction in immunosuppressive drug doses. Further decreases in immunosuppression were performed in all patients with close monitoring of renal function. All subjects were followed up for a of 18.2 +/- 5 (12 to 26) months. Two grafts were lost not due to BKVN, and one patient was lost to follow-up during this period. The latest serum creatinine in eight recipients is 113 + 20 (81 to 138) micromol/L, which is better than the renal function at diagnosis. CONCLUSION: The prevalence of BKVN in suspected BKV infection was 26%. Although the study period was short (30 months), BK viremia strongly correlated with BKVN, which seemed to be successfully treated with reduction in immunosuppression.

Persistent pulmonary hypertension of the newborn.

This article attempts to define a complicated, yet not rare disease of the neonate, which presents with extreme hypoxemia due to increased pulmonary vascular resistance, resulting in diversion of the pulmonary venous blood through persistent fetal channels, namely ductus arteriosus and foramen ovale. Pathophysiology, diagnostic approach and the various modalities of management are analyzed. Persistent pulmonary hypertension of the newborn is multi-factorial, which is reflected in the management as well. These babies are extremely labile to hypoxia and should be stabilized with minimum handling. One hundred percent oxygen and ventilation are the mainstay of treatment. The role of hyperventilation, alkalinization, various non-specific vasodilators such as tolazoline, magnesium sulphate, selective vasodilators such as inhaled nitric oxide, adenosine and the role of high frequency oscillatory ventilation and extra corporeal membrane oxygenation are discussed. With the newer modalities of management, the outlook has improved with mortality of less than 20% and fewer long-term deficits.

Sextuplets in Oman.

Use of ovulation inducing agents has increased the incidence of high order multifetal gestation. Such pregnancies are associated with increased maternal morbidity and poor perinatal outcome especially due to prematurity. Here, we report a case of sextuplet pregnancy following ovulation induction with gonadotrophins. This is the first reported case of sextuplets from Oman.

Retinopathy of prematurity in VLBW and extreme LBW babies.

OBJECTIVE: This is a hospital-based, prospective clinical study to determine the incidence, risk factors, and outcome of extreme low birth weight and very low birth weight pre-term babies with retinopathy of prematurity (ROP) at the Sultan Qaboos University Hospital, Oman. METHODS: All babies with a birth weight =/< 1500 g and gestational age =/< 32 weeks admitted in the Neonatal Unit, were screened for ROP between 4 to 6 weeks of age and staged according to the international classification and were followed up until complete vascularization of the retina. Fifty nine babies formed the study group. RESULTS: The overall incidence of ROP was 25.4% (15 out of 59), of which 6 babies had severe ROP and underwent cryotherapy/laser. All babies with ROP had a birth weight < 1250 g and were born before 31 weeks of gestation. CONCLUSION: ROP is a multifactorial disease, the immature retina of the pre-term baby being the primary factor. Incidence and severity was inversely proportional to birth weight and gestational age. Multiple logistic regression analysis showed that sepsis and total parenteral nutrition to be highly significant risk factors. Repeated blood transfusions, hypotension and congenital heart disease with left to right shunt were seen to be considerably associated with the development of ROP. A decrease in overall incidence and severity of ROP was observed in this study.