Bioinformatics analysis of wild-type ParC and S79F, S79Y mutations in Streptococcus pneumoniae.

OBJECTIVE: S79Y and S79F mutations in ParC at the fluoroquinolone binding site confer resistance to quinolones in Streptococcus pneumoniae. The aim of this study was to perform bioinformatics analysis of wild-type and mutant ParC identified in S. pneumoniae strains. MATERIALS AND METHODS: Homology models were created with Swiss Model, and the UCSF Chimera was used for the analysis and evaluation of the models. Molecular docking studies and protein-ligand interaction analysis were performed using CB-Dock developed by AutoDock Vina and Protein Ligand Interaction Profiler (PLIP), respectively. RESULTS: According to the homology modeling results, changes were observed in the physicochemical properties. Both mutant types showed a decrease in hydrophobicity (S79F: 2.0, S79Y: 0.5 - Kyte-Doolittle) and an increase in regional volume (S79F: 95 Å3, S79Y: 100 Å3). The docking scores for the wild-type, S79F, and S79Y types were 6.3, 4.9, and 5.0, respectively. The decrease in docking scores indicates weaker binding in the mutant types. The results of the PLIP analysis indicate that new bonds were formed, and the bond types changed in both mutant types, while some bonds disappeared. CONCLUSIONS: It is believed that the change in physicochemical properties caused by the mutation altered the conformation of the quinolone binding region and the bond types, numbers, and proximities of the amino acids involved in the interaction with the active substance. The results obtained from the modeling performed in this study with visualization and analysis of possible conformational, hydrophobic, and volumetric changes of only ParC mutations provided data and literature support to elucidate the mechanism. The molecular docking and PLIP results obtained in this study support both the homology modeling results and the fact that S79F and S79Y have been shown to be resistant in the literature.

Incidence and prognosis of intraabdominal hypertension and abdominal compartment syndrome in children.

PURPOSE: Intraabdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are associated with high mortality rates in children (40-60%). However, literature lacks comprehensive series in childhood. In this study, we aimed to determine the incidences of IAH and ACS, to identify high risk disorders for the development of IAH/ACS and to decrease ACS-associated mortality by early diagnosis and timely intervention. METHODS: A prospective study was performed between December 2009 and October 2010 in our institution. IAH was defined by a sustained or repeated pathological elevation in IAP≥12mmHg without a new organ failure. ACS was identified as a sustained IAP>15mmHg with a new organ dysfunction/failure. After recognition of IAH or ACS, patients underwent prompt decompressive interventions as medical or surgical procedures. RESULTS: 150 patients were enrolled to the study (86 M, 64 F). The incidences of IAH and ACS were 9% and 4%, respectively. High risk disorders were trauma, ileus, necrotizing enterocolitis, abdominal wall defects, diaphragmatic hernia and septic shock with massive fluid resuscitation. 14 patients with IAH were treated and mean IAP was decreased from 13.9±1.9mmHg to 9.2±2.1mmHg (p<0.001). None of them progressed to ACS. Six patients with ACS underwent decompressive laparotomy. Mean IAP decreased significantly from 20±3mmHg to 9±1.4mmHg (p=0.001). Vital signs like mean urine output, abdominal perfusion pressure (APP) and respiratory rate were significantly improved after surgery (p<0.05). ACS-associated mortality rate was determined as 16%. CONCLUSIONS: IAH or ACS was occurred in nearly one tenth of patients admitted to neonatal and pediatric intensive care units. High clinical suspect must be drawn on to recognize and treat these clinical complications more efficiently. Regular and frequent IAP measurement in high risk disorders is essential for early diagnosis. Lower mortality rates can be achieved by early recognition and timely intervention in children.

Complete clinical recovery of a central pontine and extrapontine myelinolysis delayed onset in a child with acute myeloblastic leukemia.

Central pontine myelinolysis (CPM) is a demyelinating disease of the pons often associated with the demyelination of extrapontine areas of the central nervous system. It typically occurs 0.5-7 days after a rapid increment in serum Na level in hyponatremic patients and may lead to death. A 2.5-year-old child with a diagnosis of acute myeloblastic leukemia developed febril neutropenia, diarrhea, gastrointestinal hemorrhage followed by pulmonary aspergillosis. He could not tolerate enteral nutrition. He was given broad spectrum antibiotics and antifungal treatment. Laboratory tests showed electrolyte abnormalities including hyponatremia, hypokalemia and hypophosphatemia in a chronic course. Twenty three days after a rapid correction of hyponatremia (16 mEq/L/24 h) he revealed flask quadriparesis, disphagia, mutism, irregular respiratory pattern and loss of cough and gag reflex. Cranial magnetic resonance showed central pontine and extrapontine myelinolysis. He required mechanical ventilation and then he regained his neurologic functions. He completed chemotherapy protocol and underwent hematopoietic stem cell transplantation. After 2.5 years of the occurrence of CPM he is in completely normal physical and neurological status. CPM is a very severe but rare disorder in children with underlying disease. In the presence of multiple etiologic factors it may reveal a delayed onset and optimum outcome can be seen even in the severe clinical presentation with adequate intensive support.

A case of herpes simplex encephalitis revealed by decompressive craniectomy.

A 15-year-old girl was referred to our hospital due to fever, headache, and vomiting of 7 days duration and focal motor convulsion at the day of referral. Her clinical signs and cerebral imaging findings were found to be compatible with herpes simplex encephalitis. In spite of prompt acyclovir administration, her consciousness deteriorated gradually. Emergent cranial magnetic resonance imaging demonstrated a shift of midline intracranial structures. Decompressive surgery resulted in partial improvement in the shift of midline intracranial structures and potentially saved the patient's life. This case report stresses the importance of proper management of increased intracranial pressure in patients with herpes simplex encephalitis.

Unusual presentation of brucellosis in a child: acute blindness.

UNLABELLED: In brucellosis, visual impairment due to optic nerve involvement is rare, and acute onset visual loss is an unusual presenting feature. We report a 15-y-old girl who had pancytopenia and who was admitted to our hospital with acute onset of bilateral blindness and fever. There was no light perception, and anterior segment and fundus examination were normal in both eyes. No other abnormal neurological findings were detected. Increased latencies and decreased amplitudes were found in visual evoked potentials. Cranial MR and CT revealed no abnormality. Blood culture was found to be positive for Brucella melitensis. Anti-Brucella treatment and high-dose metil prednisolon were given. Pancytopenia completely resolved 5 d after anti-Brucella treatment, and at the end of the third month her complaints about impaired vision were resolved. CONCLUSION: Brucellosis may present with uncommon symptoms in children. Physicians, particularly in areas where the disease is endemic, must consider this in differential diagnosis of a child with acute blindness and pancytopenia.