Pulmonary hypertension in children: the twenty-first century

Pulmonary hypertension is an elevation in pulmonary artery pressure that is associated with a spectrum of diseases and causes. Its clinical severity and presentation are widely varied. The field of study has changed immensely over the past several years. Significant knowledge has been gained in the pathophysiology, genetics, and vascular biology associated with pulmonary hypertension. These discoveries have contributed to medical interventions that have improved outcomes associated with pulmonary hypertension. This article reviews pulmonary hypertension in children, focusing on idiopathic pulmonary hypertension. Because most information is associated with children who have this form of the disease, formerly classified as primary pulmonary hypertension, medical therapy is discussed with a focus on this patient group. Additional therapeutic concepts relevant to other causes of pulmonary hypertension are highlighted.     

Synergistic interactions between MEK1/2 and histone deacetylase inhibitors in BCR/ABL+ human leukemia cells.

Interactions between the histone deacetylase inhibitor SAHA and the pharmacologic MEK1/2 inhibitor PD184352 were examined in Bcr/Abl+ human leukemia cells. Coadministration of minimally toxic concentrations of SAHA (or sodium butyrate) and PD184352 (or U0126) resulted in a synergistic increase in mitochondrial damage, caspase activation, and apoptosis in K562 and LAMA 84 cells. Similar interactions were observed in CD34+ cells from two patients with CML and in imatinib mesylate-resistant K562 cells but not in normal human CD34+ bone marrow cells. These events were associated with a marked increase in ROS generation, inactivation of ERK and Akt, downregulation of p21CIP1, Bcr/Abl, and cyclin D1, and activation of JNK. Of these events, ROS generation, ERK inactivation, and cytochrome c/AIF release were largely caspase-independent, whereas the other phenomena displayed varying degrees of caspase-dependence. Using pharmacologic and genetic approaches, generation of ROS, p21CIP1 downregulation, and inactivation of Akt and MEK were found to play significant functional roles in SAHA/PD184352-mediated lethality, whereas JNK activation and Raf-1 downregulation were determined to represent secondary events. These findings indicate that interruption of the MEK/ERK pathway substantially lowers the threshold for HDAC inhibitor-mediated oxidative injury, mitochondrial dysfunction, and apoptosis, suggesting that this approach warrants further examination in Bcr/Abl+-related malignancies.     

Surgical experience with left ventricular outflow tract obstruction in patients with complete transposition of the great arteries and essentially intact ventricular septum undergoing the Mustard operation

During a 24-year period (1963-1987), 46 infants and children with complete transposition of the great arteries (CTGA) and an essentially intact ventricular septum (IVS) have undergone surgical relief of left ventricular outflow tract obstruction (LVOTO) concurrently with the Mustard operation (MO). The obstruction was valvar in 2 patients, subvalvar in 43 and combined valvar and subvalvar in 1; the ventricular septum was intact in 42, and 4 patients had a small VSD at the time of repair. Neonatal and pre-Mustard cardiac catheterization (CC) data were analyzed to obtain LV to right ventricular peak systolic pressure ratio (LV/RVPSP) and LVOT peak systolic gradient (PSG). The mean neonatal LV/RVPSP (n = 31) was 0.79 +/- 0.04; pre-Mustard LV/RVPSP (n = 44) was 0.75 +/- 0.05; pre-Mustard LVOT PSG (n = 34) was 46.5 +/- 3.5 mmHg. Neonatal (n = 29) and pre-Mustard (n = 30) cardiac angiograms were retrospectively reviewed to analyse morphologic substrates of LVOTO. In the neonatal period, LVOTO was present in 7 patients (anatomic, n = 4; dynamic, n = 2; combined, n = 1). Immediately prior to the MO, LVOTO was present in 29 (anatomic, n = 20; dynamic n = 2; combined, n = 7). Techniques to correct LVOTO at the initial MO included pulmonary valvotomy (n = 3), ventriculomyectomy (n = 41), resection of an windsock aneurysm (n = 1), LV to pulmonary artery valved conduit (VC) (n = 1). Two patients underwent VC early postoperatively (PO) for severe residual LVOTO (both died).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemangiopericytoma like tumor — a diagnostic challenge

Haemangjopericytoma is a vascular tumour rarely seen in common practice, especially in head & neck. Hemangjopericytoma — like tumor is an even more rare entity and only 70 cases have been described arising from the nose & paranasal sinuses. The aim of this paper is to review the literature and highlight the ability of the tumor to masquerade as a less ominous, more commonly occurring benign growth of the region thereby making the diagnosis even more elusive.     

Migration of Plasticizers from Polyethylene Terephthalate and Low-Density Polyethylene Casing into Bottled Water: A Case Study From India

Mineral bottled water packed in three polymers viz., virgin polyethylene terephthalate (PET), recycled PET, and low-density polyethylene (LDPE) were investigated for the occurrence, migration, and health risk of phthalic acid esters (PAEs) at 25 °C, 35 °C, and 45 °C. The average concentration of six USEPA priority PAEs in refrigerated water samples was highest in recycled PET> LDPE > virgin PET. The highest leaching was seen at 45 °C after 2 days for LDPE water packets with ∑₆PAEs amounting to 64,300 ng/L. Similarly, for recycled PET, the highest migration was seen at 45 °C after seven days (3,800 µg/L). Bis 2-ethyl hexyl phthalate (DEHP) and di-n-butyl phthalate (DnBP) were the predominant plasticizers from PET bottles and LDPE water packets, respectively. Predicted concentration after three weeks based on best fit obtained through the polynomial model for PET bottles was seen higher than the recommended limit suggested by USEPA (6 µg/L) and WHO (8 µg/L).

     

Dexmedetomidine in a Child with Methylphenidate Intoxication

Methylphenidate intoxication, due to accidental ingestion, is a common occurrence in pediatrics. Symptoms of extreme agitation are typically controlled with benzodiazepines or barbiturates. There is, however, a legitimate risk of mechanical ventilation due to respiratory depression with increasing doses of benzodiazepines. The authors describe a case of 7-y-old girl with methylphenidate toxicity where dexmedetomidine was successfully used to manage agitation and cardiovascular stimulation without respiratory compromise.     

Embryologically Based Resection of Cervical Cancers: A New Concept of Surgical Radicality

Objectives With the objective of improving outcomes in oncological surgery, a new concept of surgical anatomy deduced from embryonic development, called ontogenetic anatomy and compartment theory of local tumor spread, is proposed by Michael Höckel from Germany. Hypothesis Compartment resection enables the preservation of functionally important tissues of different embryonic origin despite its close proximity to the tumor and incomplete resection of the compartment results in increase in local recurrences. This approach should maximize local tumor control and minimize treatment-related morbidity. Total Mesometrial Resection (TMMR) This new surgical technique has been developed and standardized over past 12 years for cervical cancer with a high local control rate without need for adjuvant radiotherapy. Conclusion This Embryological based surgery holds a great promise for management of cervical cancer. However this novel surgery needs confirmation in multi institutional settings to translate research into practice for an excellent therapeutic index.