Fourth cranial nerve palsy in pediatric patients with pseudotumor cerebri

PURPOSE: To describe three children with acute fourth cranial nerve palsy secondary to pseudotumor cerebri. METHODS: We reviewed the medical records of children younger than 18 years who were diagnosed with pseudotumor cerebri between 1977 and 1997. Pseudotumor cerebri was defined by normal neuro-imaging, elevated intracranial pressure measured by lumbar puncture, and normal cerebrospinal fluid composition. RESULTS: Three children with pseudotumor cerebri presented with vertical diplopia and clinical signs of fourth cranial nerve palsy including a hypertropia of the affected eye, which increased with adduction and ipsilateral head tilt. The fourth cranial nerve palsy resolved after reduction of the intracranial pressure in all three children. CONCLUSIONS: Fourth cranial nerve palsy may occur in children with pseudotumor cerebri and may be a nonspecific sign of elevated intracranial pressure.     

Characterization of cellulosic hot-melt extruded films containing lidocaine.

Hot-melt extrusion technology was used to produce thin films containing a model drug, lidocaine, and the cellulosic polymers hydroxypropyl cellulose (HPC) and hydroxypropyl methyl cellulose (HPMC). Two film formulations were extruded and compared, one containing only HPC and the other containing HPC:HPMC (80:20). Thermal analysis of the films using differential scanning calorimetry (DSC) suggested that the drug existed in the amorphous condition, which was confirmed by wide angle X-ray diffractometry. Sustained release of the drug was observed from both of the polymer matrices. Dissolution profiles suggested that HPMC retarded the drug release from HPC:HPMC (80:20) films. However, the mechanism of drug release from both of the films was predominantly diffusion of the drug through the polymer matrices. Incorporation of HPMC also increased both adhesive strength and work of adhesion as compared to the HPC-only films.     

Unintended consequences of policy change to watchful waiting for asymptomatic inguinal hernias

Introduction

In 2009 the Department of Health instructed McKinsey & Company to provide advice on how commissioners might achieve world class National Health Service productivity. Asymptomatic inguinal hernia repair was identified as a potentially cosmetic procedure, with limited clinical benefit. The Birmingham and Solihull primary care trust cluster introduced a policy of watchful waiting for asymptomatic inguinal hernia, which was implemented across the health economy in December 2010. This retrospective cohort study aimed to examine the effect of a change in clinical commissioning policy concerning elective surgical repair of asymptomatic inguinal hernias.

Methods

A total of 1,032 patients undergoing inguinal hernia repair in the 16 months after the policy change were compared with 978 patients in the 16 months before. The main outcome measure was relative proportion of emergency repair in groups before and after the policy change. Multivariate binary logistic regression was used to adjust the main outcome for age, sex and hernia type.

Results

The period after the policy change was associated with 59% higher odds of emergency repair (3.6% vs 5.5%, adjusted odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.03–2.47). In turn, emergency repair was associated with higher odds of adverse events (4.7% vs 18.5%, adjusted OR: 3.68, 95% CI: 2.04–6.63) and mortality (0.1% vs 5.4%, p<0.001, Fisher’s exact test).

Conclusions

Introduction of a watchful waiting policy for asymptomatic inguinal hernias was associated with a significant increase in need for emergency repair, which was in turn associated with an increased risk of adverse events. Current policies may be placing patients at risk.     

Melt extrusion with poorly soluble drugs

Melt extrusion (ME) over recent years has found widespread application as a viable drug delivery option in the drug development process. ME applications include taste masking, solid-state stability enhancement, sustained drug release and solubility enhancement. While ME can result in amorphous or crystalline solid dispersions depending upon several factors, solubility enhancement applications are centered around generating amorphous dispersions, primarily because of the free energy benefits they offer. In line with the purview of the current issue, this review assesses the utility of ME as a means of enhancing solubility of poorly soluble drugs/chemicals. The review describes major processing aspects of ME technology, definition and understanding of the amorphous state, manufacturability, analytical characterization and biopharmaceutical performance testing to better understand the strength and weakness of this formulation strategy for poorly soluble drugs. In addition, this paper highlights the potential advantages of employing a fusion of techniques, including pharmaceutical co-crystals and spray drying/solvent evaporation, facilitating the design of formulations of API exhibiting specific physico-chemical characteristics. Finally, the review presents some successful case studies of commercialized ME based products.     

Torsion in patients with superior oblique palsies: dynamic torsion during saccades and changes in Listing’s plane

Background The purpose was to assess intra- and post-saccadic torsion in superior oblique palsy (SOP) patients and the effect of surgery on torsion. Methods Eleven patients with a presumed congenital SOP and five with acquired SOP performed 10° vertical saccades over a range of ±20°. Eye movements were recorded with dual search coils. Dynamic torsion was calculated by subtracting the expected change in torsion during the saccade (based upon static torsion before and after the saccade) from the maximum intrasaccadic torsion. Eight healthy subjects were controls. We also examined the effects of surgery on dynamic torsion and the orientation of Listing’s plane in patients with congenital SOP who were operated on either by weakening of the inferior oblique muscle on the affected eye (n = 5), by recession of the inferior rectus muscle on the normal eye (n = 4) or by both procedures (n = 2). Postoperative recordings were obtained at least 1 month after surgery. Results Patients with congenital and acquired SOP showed an increased dynamic extorsion, primarily during downward saccades. Following a recession of the inferior oblique muscle in congenital SOP patients, half showed significant decreases in extorsion (up to 1.0°) during downward saccades by the affected eye. Following surgery all showed a temporal rotation of Listing’s plane (up to 15° for primary position). Conclusion Patients with a SOP show a characteristic pattern of dynamic torsion during vertical saccades differing from normals. Recession of the inferior oblique muscle leads to rotation of Listing’s plane in all congenital SOP patients and causes large changes in dynamic torsion in a subgroup of them, perhaps reflecting the heterogeneity of congenital SOP. This study was supported by the Deutsche Forschungsgemeinschaft DFG 860/2-1, Bonn Germany, Grant EYO1489, from the National Institute of Health, Bethesda, Maryland, the Abe Pollin scholarship fund, Swiss National Science Foundation Grant 3200B0-105434 and the Betty and David Koetser Foundation for Brain Research, Zurich, Switzerland.     

Induction and distribution of amylolytic activity in Cucumis sativus L. in response to virus infection

Inoculation of cucumber (Cucumis sativus L. cv. Laura) cotyledons with tobacco necrosis virus (TNV) causes both qualitative and quantitative changes in the total and fractionated protein extracts as well as in amylolytic activity. Using a specific test it was demonstrated that the virus infection strongly enhances a major band (Rf 0.0645) of amylolytic activity, predominantly located in apoplast space. The accumulation of this extracellular amylolytic activity is regulated by a time-dependent manner and is correlated with the development of necrotic lesions. The amylolytic activity may be related to degradation of starch shown to be accumulated in the immediate vicinity of necrotic lesions associated with the hypersensitive response (HR). The possible biological function of the identified amylolytic activity in the term of ,,pathosmosis" is also discussed.