A pilot study of the effects of niacin administration on free fatty acid and growth hormone concentrations in children with obesity.

CONTEXT: Children with obesity have low spontaneous growth hormone (GH) secretion. High circulating free fatty acid (FFA) concentration is believed to inhibit GH secretion in those with obesity. In adults, lipolytic inhibition with niacin lowers FFA and increases GH, but there are no prior studies in children with obesity. OBJECTIVE: The objective of the study was to determine the dose and frequency of niacin administration required to lower FFA and stimulate GH in children with obesity. DESIGN: Dose-finding study of nondiabetic children ages 6-12 years with body mass index (BMI) ≥ 95th percentile given niacin 250 mg q2h × 3 doses (n = 2), 500 mg q2h × 3 doses (n = 5) or 500 mg q1h × 4 doses (n = 5). PARTICIPANTS: Eight boys and four girls (age 9.7 ± 1.8 years; BMI 26.4 ± 3.1 kg m-2 ; BMIz 2.2 ± .25) were studied. MAIN OUTCOME: Percentage of serum FFA values that were below 0.2 mEq L-1 . GH, insulin and glucose were also measured serially. RESULTS: FFA decreased as the dose and frequency of niacin increased (p = .01). Niacin 500 mg q1h 4 doses suppressed FFA < 0.2 mEq L-1 and significantly increased GH (p = .04). Adverse effects were flushing/warmth (100%), tingling (60%) and GI complaints (20-40%). CONCLUSIONS: Niacin 500 mg q1h significantly lowered serum FFA and increased GH. These pilot data suggest that high FFA is an important suppressor of GH secretion in children with obesity.

A nine-year review of medicolegal claims in neurosurgery.

INTRODUCTION: Neurosurgery remains among the highest malpractice risk specialties. This study aimed to identify areas in neurosurgery associated with litigation, attendant causes and costs. METHODS: Retrospective analysis was conducted of 42 closed litigation cases treated by neurosurgeons at one hospital between March 2004 and March 2013. Data included clinical event, timing and reason for claim, operative course and legal outcome. RESULTS: Twenty-nine claims were defended out of court and twelve were settled out of court. One case required court attendance and was defended. Of the 42 claims, 28, 13 and 1 related to spinal (0.3% of caseload), cranial (0.1% of caseload) and peripheral nerve (0.07% of caseload) surgery respectively. The most common causes of claims were faulty surgical technique (43%), delayed diagnosis/misdiagnosis (17%), lack of information (14%) and delayed treatment (12%), with a likelihood of success of 39%, 29%, 17% and 20% respectively. The highest median payouts were for claims against faulty surgical technique (£230,000) and delayed diagnosis/misdiagnosis (£212,650). The mean delay between clinical event and claim was 664 days. CONCLUSIONS: Spinal surgery carries the highest litigation risk versus cranial and peripheral nerve surgery. Claims are most commonly against faulty surgical technique and delayed diagnosis/misdiagnosis, which have the highest success rates and payouts. In spinal surgery, the most common cause of claims is faulty surgical technique. In cranial surgery, the most common cause is lack of information. Claims may occur years after the clinical event, necessitating thorough contemporaneous documentation for adequate future defence. We emphasise thorough patient consultation and meticulous surgical technique to minimise litigation in neurosurgical practice.

An extended role for CT in the emergency diagnosis of malignant spinal cord compression.

AIM: To evaluate the usefulness of computed tomography (CT) for triaging between urgent transfer to a neurosurgical unit and delayed magnetic resonance imaging (MRI) in the local hospital. MATERIALS AND METHODS: Radiologists blinded to the MRI findings scored CT images from 1-5 using a novel grading system based on the degree of cord compression observed in 44 patients. Seventy separate levels were scored. The observers' CT scores were compared with the MRI findings. All scoring radiologists were specialist registrars at different stages of training. RESULTS: Agreement between CT and MRI scores for metastatic spinal cord compression (MSCC) were high with Cohen's weighted Kappa score 0.70 (p<0.001, 95% CI 0.65 to 0.75). CT has a sensitivity of 89% and specificity of 92% for MSCC. Half the false-positive and false-negative results came from a single junior radiologist who would not normally report CT or MRI studies unsupervised. The best CT-MRI agreement was from the most senior trainee radiologist. CONCLUSIONS: Spinal findings on routine staging whole-body CT combined with clinical findings are sufficient to determine which patients with MSCC can safely wait for MRI the next working day at the local hospital and those who need emergency transfer to a neurosurgical unit for MRI and possible surgical decompression.

Blunt traumatic vertebral artery injury: a clinical review.

Blunt traumatic vertebral injury (TVAI) is frequently associated with head and neck injury and is being detected with increasing frequency due to improved imaging of the trauma patient. In a few cases, it can lead to potentially fatal posterior circulation ischaemia There is debate in the literature regarding whether TVAI should be actively screened for and, if so, how. Management of TVAI may be conservative, medical (antiplatelet agents or anticoagulation), endovascular or open surgery. We review the literature concerning the mechanisms and presentation of TVAI following blunt injury and the current screening recommendations. Management strategies proposed are based on the radiological grade and clinical severity of TVAI, where high-grade symptomatic injuries and high-grade injuries in patients where anticoagulation is contraindicated are treated endovascularly and asymptomatic or low-grade injuries are managed with anticoagulation where it is not contraindicated. Follow-up is via CT angiography to assess for resolution of the injury.

Symptomatic venous sinus thrombosis following bone wax application to emissary veins.

A retrosigmoid craniectomy was performed for acoustic neuroma during which bone wax was used to control emissary vein bleeding. Postoperatively the patient developed an extensive venous thrombosis due to wax in the sigmoid sinus from which she recovered. We discuss this rare complication of posterior fossa surgery.

The value of interhospital transfer and emergency MRI for suspected cauda equina syndrome: a 2-year retrospective study.

INTRODUCTION: The timing of surgery in cauda equina syndrome due to prolapsed intervertebral disc remains controversial. Assessment of these patients requires magnetic resonance imaging (MRI), which is of limited availability outside normal working hours in the UK. PATIENTS AND METHODS: We reviewed radiological results in all patients undergoing emergency MRI within our unit for suspected cauda equina syndrome over a 2-year period, and all subjects undergoing emergency lumbar discectomy for cauda equina syndrome within the same period. Outcome measures were: proportion of positive findings in symptomatic patients and proportion of patients referred with diagnostic MRI scans undergoing emergency surgery. We also assessed outcomes of patients having surgery for cauda equina syndrome in terms of improvement of pain, sensory and sphincter disturbance. RESULTS: A total of 76 patients were transferred for assessment and 'on-call' MRI; 27 were subsequently operated upon. Only 5 proceeded to emergency discectomy that night (prior to next scheduled list). This may be due to delays in timing--from referral to acceptance, to arrival in the department, to diagnostic scan and to theatre. With the second group of patients, 43 had emergency discectomy for cauda equina syndrome during the study period. Of these, 6 patients had an out-of-hours MRI at our hospital for assessment (one patient living locally). Most surgically treated patients experienced improvement in their pain syndrome, with approximately two-thirds experiencing improvement in sensory and sphincter disturbance. CONCLUSIONS: These data support a policy of advising MRI scan for cauda equina syndrome at the earliest opportunity within the next 24 h in the referring hospital, rather than emergency transfer for diagnostic imaging which has a relatively low yield in terms of patients operated on as an emergency.

Congenital disseminated neurofibromatosis type 1: a clinical and molecular case report.

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition with a birth incidence of 1/3,500. Around 50% of cases are due to new mutations. The NF1 gene maps to 17q11.2 and encodes neurofibromin. NF1 is a "classical" tumor suppressor gene. Congenital disseminated NF1 is rare with just two cases previously reported. We present a deceased baby with congenital disseminated NF1 in whom we performed molecular studies. A germline mutation (R461X) in exon 10a of the NF1 gene was found. A 2 bp deletion (3508delCA) in codon 1170 of exon 21 was identified in DNA derived from some tumor tissue. Loss of heterozygosity in NF1 and TP53 was observed in other tumor samples. No microsatellite instability was observed in the tumor samples. This is the first report of molecular analysis of the NF1 locus in a patient with disseminated congenital neurofibromatosis. This case had a de novo germline mutation in NF1 and three documented somatic mutations in the NF1 and TP53 genes in tumor specimens.

Posterior approach vertebrectomy in the thoracolumbar spine with expandable cage reconstruction: indications and techniques based on eight cases.

We present a series of eight patients undergoing circumferential neural decompression and stabilization of the thoracolumbar spine via a single midline posterior approach, with complete vertebrectomy for a variety of indications. Four had primary tumours, two secondary tumours, one patient had tuberculosis and one had delayed deformity due to trauma. This single posterior approach is made possible via the use of an expandable cage that may be expanded in situ to offer anterior and middle column reconstruction. There were no major neurological complications and all patients with deficits improved postoperatively. Extensive posterior fixation was avoided with five patients undergoing a one above/one below fixation and three undergoing a two above/two below fixation. When combined with pedicle screw and rod fixation this anterior reconstruction makes a sound construct. The flexibility of this approach in the thoracolumbar spine, some of the biomechanical advantages and pitfalls are considered.

Masson's tumour in the right parietal lobe after stereotactic radiosurgery for cerebellar AVM: case report and review.

We present a 50-year-old patient who had undergone stereotactic radiosurgery for a cerebellar vermian arteriovenous malformation. On routine surveillance MR imaging a lesion suggestive of a meningioma was demonstrated and removed. Histologically it was found to be intravascular papillary endothelial hyperplasia (Masson's tumour). The characteristic radiological and histological findings are presented. Aspects of management of this rare tumour are discussed. Given that cases are often found in combination with a vascular abnormality, we discuss the possibility of a change in local haemodynamics after radiosurgery promoting development of this tumour.

Cryptic mosaicism for monosomy 20 identified in renal tract cells.

We report a post-natal case of mosaic aneuploidy for chromosome 20 in a 4 months old male baby with an abnormal phenotype including dysmorphic features (asymmetric facial growth), ventricular septal defect, hypotonia and bilateral vesicoureteric reflux. Conventional cytogenetics on peripheral blood showed 1 cell of 200 with 47,XY,+20. Further investigations using fluorescent in situ hybridization (FISH) on a urine sample, with a centromere probe for chromosome 20, revealed 39 of 50 cells giving one signal indicative of monosomy 20. FISH analysis of a buccal smear was consistent with disomy 20 as was conventional cytogenetics on skin fibroblasts. This is the fourth reported case of mosaic monosomy 20, the second case where monosomy 20 is present with a trisomy 20 cell and the first case with each aneuploidy found in two separate tissues. The identification of mosaicism is a difficult task since the abnormal cells can be present only in certain tissues and may disappear with selection as the fetus develops, thus leading to single-cell abnormalities that may get dismissed (pseudomosaicism). The use of FISH in this case was crucial in identifying the cryptic mosaic monosomy 20 cell line. The likely mechanism of origin is post-zygotic nondisjunction giving rise to monosomy, disomy and trisomy cell(s) in the same or different tissues. Although no other trisomy 20 cells were found, the abnormal phenotype plus the finding of a monosomy 20 cell line make this mechanism the most plausible explanation. Had we dismissed the single-cell abnormality, the cryptic mosaicism of monosomy 20 would not have been identified. A detailed analysis of all tissues accessible in conjunction with careful consideration of all clinical information available is the best course of action in suspected mosaicism.

Aneurysmal subarachnoid haemorrhage in a patient with thyrotoxicosis.

A case of subarachnoid haemorrhage secondary to rupture of an intracranial aneurysm occurring in a patient with new-onset, frank thyrotoxicosis is described. This unusual case highlights the dilemma of whether to continue beta-blockers such as propanolol for frank thyrotoxicosis, or whether to assign higher priority to maintaining adequate cerebral perfusion pressure in established ischaemic deficit due to vasospasm. In a complicated case such as this, the Maudsley Mentation Test score and perfusion CT scanning are two useful adjuncts for the early detection and evaluation of the course of ischaemic deficit.

Growing skull fracture in the absence of a dural tear.

A case of growing skull fracture associated with unrecognized extradural haematoma is presented together with the relevant radiology. The pathophysiology of growing skull fracture is reviewed in light of this previously unreported case.

Prenatal diagnosis of cri du chat (5p-) syndrome in association with isolated moderate bilateral ventriculomegaly.

A case of prenatally detected cri du chat syndrome (5p-) is reported. Amniocentesis was performed following an abnormal ultrasound finding of isolated moderate bilateral ventriculomegaly. The karyotype showed a terminal deletion of the short arm of chromosome 5 including the critical region 5p15 for cri du chat syndrome. This was confirmed by fluorescence in situ hybridisation (FISH). Isolated mild ventriculomegaly may be a non-specific marker for cri du chat syndrome.

The Giardia genome project database.

The Giardia genome project database provides an online resource for Giardia lamblia (WB strain, clone C6) genome sequence information. The database includes edited single-pass reads, the results of BLASTX searches, and details of progress towards sequencing the entire 12 million-bp Giardia genome. Pre-sorted BLASTX results can be retrieved based on keyword searches and BLAST searches of the high throughput Giardia data can be initiated from the web site or through NCBI. Descriptions of the genomic DNA libraries, project protocols and summary statistics are also available. Although the Giardia genome project is ongoing, new sequences are made available on a bi-monthly basis to ensure that researchers have access to information that may assist them in the search for genes and their biological function. The current URL of the Giardia genome project database is www.mbl.edu/Giardia.

Search strategies in syntactic reanalysis.

We first consider the nature of syntactic reanalysis, paying particular attention to questions about whether and how it differs from the construction of an initial analysis, such as whether it is encapsulated or whether alternatives are considered in parallel or not. We then outline different strategies that the processor may use in reanalysis, and review the relevant evidence. We show that our experimental evidence is compatible with an encapsulated serial search strategy.

Wide-coverage probabilistic sentence processing.

This paper describes a fully implemented, broad-coverage model of human syntactic processing. The model uses probabilistic parsing techniques, which combine phrase structure, lexical category, and limited subcategory probabilities with an incremental, left-to-right "pruning" mechanism based on cascaded Markov models. The parameters of the system are established through a uniform training algorithm, which determines maximum-likelihood estimates from a parsed corpus. The probabilistic parsing mechanism enables the system to achieve good accuracy on typical, "garden-variety" language (i.e., when tested on corpora). Furthermore, the incremental probabilistic ranking of the preferred analyses during parsing also naturally explains observed human behavior for a range of garden-path structures. We do not make strong psychological claims about the specific probabilistic mechanism discussed here, which is limited by a number of practical considerations. Rather, we argue incremental probabilistic parsing models are, in general, extremely well suited to explaining this dual nature--generally good and occasionally pathological--of human linguistic performance.