Primary cerebellar glioblastomas multiforme in children. Report of four cases

Primary cerebellar glioblastomas multiforme are exceedingly rare in children. The authors therefore retrospectively characterized the clinical behavior and pathological features of these tumors. A review of the database at the Hospital for Sick Children, Toronto, Canada revealed four patients with cerebellar tumors that displayed significant pleomorphism, hypercellularity, mitoses, and necrosis with pseudopalisading. The authors performed a detailed clinical, radiological, histological, and immunohistochemical analysis of the tumors in these four children (three boys and one girl; average age at presentation 7 years; range 21 months-15 years). Magnetic resonance imaging and computerized tomography most commonly revealed a large lesion with minimal edema, inhomogeneous contrast enhancement, and a discrete border. Tumor resection was subtotal in one patient and gross total in three patients. Immunostaining of the tumor cells with antisera to glial fibrillary acidic protein and vimentin was positive in varying degrees. Initial adjuvant therapy consisted of local radiation only (one patient), chemotherapy only (one patient), and radiation and chemotherapy (one patient). One patient received no adjuvant therapy. Tumor recurrence was documented in all patients: two local recurrences (at 3.5 and 7 months), one spinal recurrence (at 14 months), and one local recurrence with ventricular and spinal spread (at 8 months). Ultimately, three of the four patients developed leptomeningeal tumor spread. Patient follow up ranged from 8 to 17 months (mean 12.5 months). Three patients were dead at last follow up with a mean survival of 15 months. The prognosis for patients with cerebellar glioblastomas is extremely poor, and the tumor has a tendency for cerebrospinal fluid dissemination. The optimal management of patients harboring of these difficult-to-treat tumors, including the role of craniospinal radiation and chemotherapy, has not yet been achieved.     

Late death after extracorporeal membrane oxygenation for congenital diaphragmatic hernia

PURPOSE: The aim of this study was to determine the long-term outcome of neonates who required extracorporeal membrane oxygenation (ECMO) for respiratory insufficiency associated with congenital diaphragmatic hernia (CDH). METHODS: All neonates born with CDH, who required ECMO (oxygenation index over 40 in the presence of maximal support) during a 6-year period, were reviewed. The median duration of follow-up for survivors was 14 months (range, 9 to 22 months). RESULTS: Of 72 neonates with CDH, 11 (15%) required ECMO. The median age at the start of ECMO was 2 days (range, 1 to 4); duration was 9 days (range, 4 to 17); post-ECMO ventilation was 27 days (range, 8 to 86); and stay in intensive care unit, 33 days (range, 8 to 133). Three patients survived and are not oxygen dependent. There were three early deaths at 9 to 16 days and five late deaths at a median of 6 months (range, 2 to 32 months) secondary to chronic lung disease (n = 3) and infection (n = 2). Four of the five patients with late deaths were oxygen dependent at discharge from hospital. Three of the late death patients and one survivor underwent a fundoplication for gastrooesophageal reflux. CONCLUSIONS: Neonates born with CDH and requiring ECMO had a significant late mortality. Follow-up for more than 1 year is indicated to assess the benefit of ECMO for this diagnosis. The authors report only three long-term survivors from 11 ECMO patients selected from a total of 72 neonates with CDH.     

Mutation rates among RNA viruses

The rate of spontaneous mutation is a key parameter in modeling the genetic structure and evolution of populations. The impact of the accumulated load of mutations and the consequences of increasing the mutation rate are important in assessing the genetic health of populations. Mutation frequencies are among the more directly measurable population parameters, although the information needed to convert them into mutation rates is often lacking. A previous analysis of mutation rates in RNA viruses (specifically in riboviruses rather than retroviruses) was constrained by the quality and quantity of available measurements and by the lack of a specific theoretical framework for converting mutation frequencies into mutation rates in this group of organisms. Here, we describe a simple relation between ribovirus mutation frequencies and mutation rates, apply it to the best (albeit far from satisfactory) available data, and observe a central value for the mutation rate per genome per replication of micro(g) approximately 0.76. (The rate per round of cell infection is twice this value or about 1.5.) This value is so large, and ribovirus genomes are so informationally dense, that even a modest increase extinguishes the population.     

Primary bacterial colonization of implant surfaces

The purpose of this study was to assess the effects of modifying titanium surfaces, in terms of wettability, roughness, and mode of sterilization, on the ability of the oral bacterium Streptococcus sanguis to colonize. An in vitro model system was developed. All surfaces were colonized by the bacteria, but to significantly different levels. Titanium samples that exhibited rough or hydrophobic (low wettability) surfaces, along with all autoclaved surfaces, were preferentially colonized (P < .01). Titanium surfaces that had been repeatedly autoclaved were colonized with the levels of bacteria 3 to 4 orders of magnitude higher than other modes of sterilization. This may have implications relative to the commonly used method of autoclaving titanium implants, which may ultimately enhance bacterial biofilm formation on these surfaces.     

Cephalomedullary nails in the treatment of high-energy proximal femur fractures in young patients: a prospective, randomized comparison of trochanteric versus piriformis fossa entry portal

OBJECTIVE: The purpose of this study is to compare a cephalomedullary nail that uses a piriformis fossa starting point to one that uses a trochanteric starting point, in the treatment of high-energy proximal femur fractures in young patients. Our hypothesis was that a nail that uses a trochanteric starting point would result in less blood loss than a nail that uses a piriformis fossa starting point. DESIGN: Prospective, randomized. SETTING: Level 1 trauma center. PATIENTS: Thirty-four consecutive patients aged between 18 and 50 years who sustained a subtrochanteric, intertrochanteric, or ipsilateral femoral neck/shaft fracture due to a high-energy injury were enrolled. INTERVENTION: Patients were randomized to have their fractures repaired with a Russell-Taylor Recon Nail or Howmedica Long Gamma Nail. Surgery was performed on a fracture table, in supine or lateral position according to the surgeon's preference. Direct fracture exposure was avoided. Reduction was obtained through traction, patient positioning, and manual pressure. If necessary, stab-wound incisions were made to introduce instruments to improve reduction. Intramedullary reamers were used, and all nails were statically locked. Bone grafting was not used. MAIN OUTCOME MEASURES: Blood loss, incision length, duration of surgery, and body mass index were recorded for each patient. Surgeon's assessment of ease of use of the device and quality of reduction were noted. Patients were to be followed up to assess fracture union. Hip and knee ranges of motion at latest follow-up were measured. Radiographs obtained at the time of union were assessed for varus malalignment. Return to work status was recorded, and the Harris Hip Score was used to assess hip function. RESULTS: There were 17 patients in each group. The 2 groups did not differ with regard to blood loss, incision length, and duration of surgery or intraoperative complications. Body mass index was significantly linked to duration of surgery (P<0.001) and incision length (P<0.001). Surgeon's assessment of ease of use and reduction quality for the two devices did not differ. The rate of varus malunion did not differ between the 2 groups. Two patients were lost to follow-up before fracture union. All other fractures healed with no need for bone grafting or other procedures to obtain union. One obese patient developed a wound infection that resolved after debridement and a course of antibiotics. A total of 6 patients were lost prior to their 1-year follow-up visit. Among the remaining 28 patients, at an average follow-up of 14 months, no difference was noted between the 2 groups with regard to return to work status, Harris Hip Score, or hip and knee ranges of motion. CONCLUSIONS: Both devices yield predictably good results in these difficult fractures. We found no difference between the two devices with regard to incision length, duration of surgery, blood loss, reduction, ease of use, union rate, complication rate, or outcome.     

Obstetric regional blocks for women with multiple sclerosis: a survey of UK experience

BACKGROUND: There has been a reluctance to use regional blocks for women with multiple sclerosis as effects on the course of the disease are unclear. We assessed the views of UK consultant obstetric anaesthetists regarding management of women with multiple sclerosis. METHODS: Following Obstetric Anaesthetists' Association approval a questionnaire was sent to UK consultant members. Opinions were sought on antenatal assessment, labour analgesia, anaesthesia for elective and emergency caesarean section, and modification in technique for those with multiple sclerosis. Enquiries were made of postnatal problems ascribed to regional blocks. RESULTS: Of the 592 replies analysed, 91% of respondents had seen fewer than 10 cases of multiple sclerosis in the past 10 years. Antenatal assessment was recommended by many with postnatal relapse most commonly discussed (64%). Many highlighted the need for informed consent and minimising local anaesthetic dose. For labour analgesia 79% would perform a regional block; a further 20% would do so in certain circumstances. For elective caesarean section, epidural rather than spinal anaesthesia was preferred by 4%; 2% would not use a regional block, preferring general anaesthesia. For emergency caesarean section with time only for single-shot spinal, 3% would give a general anaesthetic. Deterioration of symptoms after delivery were reported by 20% with 3% attributing symptoms such as prolonged block, leg weakness, bladder dysfunction and postnatal relapse to regional blocks. CONCLUSION: Most UK anaesthetists would perform regional blocks for labour and caesarean section in multiple sclerosis, although the experience of each anaesthetist is limited. Many emphasised the need for thorough pre-assessment and informed consent.     

Influence of various central moieties on the hypolipidemic properties of long hydrocarbon chain diols and diacids

A series of long (11-15) hydrocarbon chain diols and diacids with various central functional groups and terminal gem-dimethyl or -methyl/aryl substituents was synthesized and evaluated in both in vivo and in vitro assays for its potential to favorably alter lipid disorders including metabolic syndrome. Compounds were assessed for their effects on the de novo incorporation of radiolabeled acetate into lipids in primary cultures of rat hepatocytes, as well as for their effects on lipid and glycemic variables in obese female Zucker fatty rats, Crl:(ZUC)-faBR. The most active compounds were hydroxyl-substituted symmetrical diacids and diols with a 13-atom chain and terminal gem-dimethyl substituents. Furthermore, biological activity was enhanced by central substitution with O, C=O, S, S=O compared to the methylene analogues and was diminished for compounds with central functional groups such as carbamate, ester, urea, acetylmethylene, and hydroxymethylene.     

Differential Effects of Two Types of Formative Assessment in Predicting Performance of First-year Medical Students

Formative assessments are systematically designed instructional interventions to assess and provide feedback on students’ strengths and weaknesses in the course of teaching and learning. Despite their known benefits to student attitudes and learning, medical school curricula have been slow to integrate such assessments into the curriculum. This study investigates how performance on two different modes of formative assessment relate to each other and to performance on summative assessments in an integrated, medical-school environment. Two types of formative assessment were administered to 146 first-year medical students each week over 8 weeks: a timed, closed-book component to assess factual recall and image recognition, and an un-timed, open-book component to assess higher order reasoning including the ability to identify and access appropriate resources and to integrate and apply knowledge. Analogous summative assessments were administered in the ninth week. Models relating formative and summative assessment performance were tested using Structural Equation Modeling. Two latent variables underlying achievement on formative and summative assessments could be identified; a “formative-assessment factor” and a “summative-assessment factor,” with the former predicting the latter. A latent variable underlying achievement on open-book formative assessments was highly predictive of achievement on both open- and closed-book summative assessments, whereas a latent variable underlying closed-book assessments only predicted performance on the closed-book summative assessment. Formative assessments can be used as effective predictive tools of summative performance in medical school. Open-book, un-timed assessments of higher order processes appeared to be better predictors of overall summative performance than closed-book, timed assessments of factual recall and image recognition. This research was presented at the 86th Annual Meeting of the American Educational Research Association (AERA) in Montreal, Canada, April 11–15, 2005.