Characterization of Ribosomal Binding and Antibacterial Activities Using Two Orthogonal High-Throughput Screens

We report here the affinity and antibacterial activity of a structurally similar class of neomycin dimers. The affinity of the dimer library for rRNA was established by using a screen that measures the displacement of fluorescein-neomycin (F-neo) probe from RNA. A rapid growth inhibition assay using a single drug concentration was used to examine the antibacterial activity. The structure-activity relationship data were then rapidly analyzed using a two-dimensional ribosomal binding-bacterial inhibition plot analysis.     

Costs and outcomes of acute kidney injury (AKI) following cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is a recognized complication of cardiac surgery; however, the variability in costs and outcomes reported are due, in part, to different criteria for diagnosing and classifying AKI. We determined costs, resource use and mortality rate of patients. We used the serum creatinine component of the RIFLE system to classify AKI. METHODS: A retrospective cohort study was conducted from the electronic data repository at the University of Pittsburgh Medical Center of patients who underwent cardiac surgery and had an elevation (>or=0.5 mg/dl) of serum creatinine postoperatively. Data were compared to age- and APACHE III-matched controls. Cost, mortality and resource use of AKI patients were determined postoperatively for each of the three RIFLE classes on the basis of changes in serum creatinine. RESULTS: Of the 3741 admissions, 258 (6.9%) had AKI and were classified as RIFLE-R 138 (3.7%), RIFLE-I 70 (1.9%) and RIFLE-F 50 (1.3%). Total and departmental level costs, length of stay (LOS) and requirement for renal replacement therapy (RRT) were higher in AKI patients compared to controls. Statistically significant differences in all costs, mortality rate and requirement for RRT were seen in the patients stratified into RIFLE-R, RIFLE-I and RIFLE-F. Even patients with the smallest change in serum creatinine, namely RIFLE-R, had a 2.2-fold greater mortality, a 1.6-fold increase in ICU LOS and 1.6-fold increase in total postoperative costs compared to controls. DISCUSSION: Costs, LOS and mortality are higher in postoperative cardiac surgery patients who develop AKI using RIFLE criteria, and these values increase as AKI severity worsens.     

Surgical removal of unilateral vestibular schwannomas after failed Gamma Knife radiosurgery

One of the primary criticismes of vestibular schwannoma (VS) radiosurgery is that the risk of surgical morbidity is increased for patients whose tumor progresses after the procedures. We reviewed the French experience of operated patients after failed Gamma Knife radiosurgery. From July 1992 to January 2002, 25 out of the 1000 treated patients underwent another treatment procedure for a gamma knife failure. Excluding the NF2 patients, 21 patients have been operated and the present study shows the data collected for 20 of them. In order to analyze the difficulties observed during the surgery, a questionnaire was filled by the surgeons. The mean interval between radiosurgery and removal was 36 Months, from 10 to 83 Months. The mean increase in Volume was 559% (37 to 3036%, median 160%). Evolution of the Koos grading was found from 8 grade II, 10 grade III et 2 grade IV to 10 grade III and 10 grade IV. Patients have been operated for radiological tumor growth in 7 cases and for clinico-radiological evolution in 13 cases. In 9 cases, the surgeon considered that he had to face unusual difficulties mainly because of adhesion of the tumor to neurovascular structures. Tumor removal was total in 14 cases, near total in 4 cases and subtotal in 2 cases. One case of venous infarction was noticed at the second day following surgery responsible of hemiparesis and aphasia that gradually recovered. At last follow-up examination, facial nerve was normal (House and Brackmann grade I and II) in 10 cases while it was a grade III in 7 cases and grade IV and V in 3 cases. We recommend that the decision for surgical removal of growing vestibular schwannoma after Gamma Knife treatment should be done after a sufficiently long follow-up period. Our results show that the quality of removal and of facial nerve preservation might be impaired by radiosurgery in half of cases. However these results do not support a change in our policy of radiosurgical treatment of small to medium size vestibular schwannoma.     

Intraoperative fluid administration volumes during pediatric liver transplantation and postoperative outcomes: A multicenter analysis

Introduction

Fluid administration is an important aspect of the management of children undergoing liver transplantation and may impact postoperative outcomes. Our aim was to evaluate the association between volume of intraoperative fluid administration and our primary outcome, the duration of postoperative mechanical ventilation following pediatric liver transplantation. Secondary outcomes included intensive care unit length of stay and hospital length of stay.

Methods

We conducted a multicenter, retrospective cohort study using electronic data from three major pediatric liver transplant centers. Intraoperative fluid administration was indexed to weight and duration of anesthesia. Univariate and stepwise linear regression analyses were conducted.

Results

Among 286 successful pediatric liver transplants, the median duration of postoperative mechanical ventilation was 10.8 h (IQR 0.0, 35.4), the median intensive care unit length of stay was 4.3 days (IQR 2.7, 6.8), and the median hospital length of stay was 13.6 days (9.8, 21.1). Univariate linear regression showed a weak correlation between intraoperative fluids and duration of ventilation (r² = .037, p = .001). Following stepwise linear regression, intraoperative fluid administration remained weakly correlated (r² = .161, p = .04) with duration of postoperative ventilation. The following variables were also independently correlated with duration of ventilation: center (Riley Children's Health versus Children's Health Dallas, p = .001), and open abdominal incision after transplant (p = .001).

Discussion

The amount of intraoperative fluid administration is correlated with duration of postoperative mechanical ventilation in children undergoing liver transplantation, however, it does not seem to be a strong factor.

Conclusions

Other modifiable factors should be sought which may lead to improved postoperative outcomes in this highly vulnerable patient population.     

Cystothecostomy: a new technique to treat long segment spinal extradural arachnoid cyst

Pathogenesis and treatment of the spinal arachnoid cyst has not been well established. A novel method of treatment of a long segment spinal arachnoid cyst is being presented in a 9-year-old boy. He presented to us with a slowly progressive spastic paraparesis. MRI revealed dorsal epidural arachnoid cyst extending from T7 vertebral body to L1 body producing marked cord compression. In order to save the child from a long segment laminectomy or laminoplasty, a new minimally invasive technique was devised. In this technique L1 laminectomy was performed under local anaesthesia, and the cyst was communicated to thecal sac by making an interconnecting stoma. We named this procedure as cystothecostomy. There was gradual neurological recovery after the procedure.     

How successful is the conservative management of pelvi‐ureteric junction obstruction in adults?

OBJECTIVE

To assess the conservative management of pelvi‐ureteric junction obstruction (PUJO), according to severity, accepted in paediatric urology but rarely reported in adults.

PATIENTS AND METHODS

A series of 23 patients (median age 58 years, 17 men and six women) with asymptomatic or minimally symptomatic PUJO were managed conservatively. The patients’ age, preference and comorbidities were considered. The diagnosis of PUJO was based on intravenous urography and isotopic renography. After stringently reviewing the renograms based on relative renal function (RRF) and output efficiency (OE), 15 patients had an OE consistent with definitive PUJO. One patient had no further imaging due to associated comorbidities. Ten patients had right PUJO, three left and one with bilateral PUJO, with unilateral conservative management. The follow‐up included annual renography and clinical consultation. Laparoscopic pyeloplasty was considered for patients with a >10% loss of RRF and/or <40% RRF during the follow‐up.

RESULTS

Overall, 14 of 15 patients had renograms during the follow‐up. The mean RRF of the affected kidney at diagnosis was 48.6% which marginally decreased to 46.7% after a median (range) follow‐up of 44 (23–75) months. The RRF of 11 patients remained stable and in three decreased significantly (median 11% RRF), requiring pyeloplasty. None of the patients became symptomatic throughout the follow‐up.

CONCLUSION

In asymptomatic adults the conservative management of PUJO appears to be safe during a short‐ to medium‐term follow‐up. We recommend that patients are regularly followed with renography and seen promptly should they become symptomatic. A longer follow‐up is needed in a larger group to confirm these findings.     

Secretin Provocation: Gastrin Results in Various Clinical Situations

Our previous secretin provocation studies in normal volunteers and unoperated duodenal ulcer patients suggested that the gastrin rise in gastrinoma may be an exaggeration of the normal response rather than paradoxical. We report further studies in various clinical settings having normogastrinemia (normal, n = 17; unoperated duodenal ulcer, n = 13; primary hyperparathyroidism, n = 7) and hypergastrinemia (postvagotomy, n = 5; hypochlorhydria, n = 7; achlorhydria, n = 10; chronic renal failure, n = 10; gastrinoma, n = 5). Under all nongastrinoma conditions, there were similar gastrin rises of 9-19% between 2 and 5 min after bolus intravenous GIH secretin (2 CU/kg), which fell to baseline by 8 min, except for chronic renal failure. In chronic renal failure, gastrin remained elevated from 7 to 30 min and was significantly different (p less than 0.05) at 10-30 min compared to all other nongastrinoma conditions except hyperparathyroidism. Peak rises occurred within 5 min in all entities, but only three gastrinoma patients had positive secretin provocation tests by the predefined criterion of a gastrin rise greater than 200 pg/ml. The results of secretin provocation in various clinical entities with and without hypergastrinemia further support the hypothesis that the gastrin rise in gastrinoma is an exaggeration of the normal response. The prolonged gastrin rise seen in chronic renal failure may be due to altered renal clearance, inasmuch as other hypergastrinemic states had responses similar to normal and duodenal ulcer.     

GC-FID,Antioxidants Analysis and Antimicrobial,Anti-Inflammatory,Anti-Diabetic Activities of Tisanes Derived from Underutilized Lemon Grass Cymbopogon khasianus (Hack.)

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Cymbopogon khasianus (Hack.) is widely distributed and an underutilized plants in tropical and subtropical...