Central adrenal insufficiency following traumatic brain injury: a missed diagnosis in the critically injured.

BACKGROUND: High-dose steroid administration is no longer recommended in the treatment of acute traumatic brain injury (TBI) as it failed to prove beneficial in improving patients' outcome. However, a masked benefit of steroid administration in TBI management was that it provided corticosteroid replacement therapy in patients with TBI-related central adrenal insufficiency. CASE PRESENTATION: We report the case of a 12-year-old boy who suffered a severe TBI from a motor vehicle accident that resulted in complete deficiency of anterior pituitary function. Central adrenal insufficiency was not ruled out by a near normal response to a low-dose ACTH test performed on D11. CONCLUSION: Consideration should be given to the empirical treatment of TBI pediatric patients with stress doses of corticosteroids if injury to the hypothalamus or pituitary gland is possible until a formal assessment of the hypothalamic-pituitary-adrenal axis can be made.

Ophthalmological outcomes of patients treated for pineal region tumors.

OBJECTIVE The ophthalmological outcomes of children treated for pineal tumors have received limited attention in the literature. METHODS This paper reviews the outcomes of 29 children treated for pineal and posterior third ventricular tumors in the contemporary era using chemotherapy, radiotherapy, and resection as defined by the histology and/or marker profile of the tumor. RESULTS At the time of diagnosis, all patients except 1 had hydrocephalus and all had ophthalmological involvement. Papilledema was found in 69% of patients. Seventy-five percent of patients had partial or complete Parinaud's syndrome, and diplopia or blurred vision was noted in the remaining patients. Visual acuity was impaired in 8 patients. Outcomes were dependent on the histology of the tumor and the treatment required. Those patients who did not requiring resection showed a lower rate of ophthalmological worsening during treatment and greater long-term improvement, in particular with respect to up-gaze palsy. Patients who underwent resection for postchemotherapy residual disease or primary resection showed greater worsening during treatment and lesser degrees of recovery. All patients with impaired visual acuity improved with treatment. CONCLUSIONS As the mortality of germ cell and other pineal tumors decreases, posttreatment morbidity remains, specifically that related to convergence nystagmus, accommodation, and diplopia. In addition to survival, ophthalmological morbidity should be reported in studies concerning the outcomes of treatment for pineal neoplasms.

Cerebellar cavernous malformation in pediatric patients: defining clinical, neuroimaging, and therapeutic characteristics.

OBJECT: Cerebellar cavernous malformations (CCMs) have not been specifically described in the pediatric age group. Authors of this study, after considering the published literature, describe the characteristic clinical, radiological, and surgical features of CCM in children. METHOSDS: Patients younger than 18 years of age who were known to have CCM and had undergone surgery between 1992 and 2014 at the authors' institution were reviewed. Pediatric CCM cases reported in the literature (case reports and cases included in series on CMs in the pediatric age group) were also analyzed for specific features of this entity. RESULTS: Four male patients and 1 female patient (2.5-14 years of age) with CCM presented acutely with severe headache followed by cerebellar dysfunction. In all patients, neuroimaging (cranial CT and MRI) demonstrated hemorrhagic cerebellar lesions with heterogeneous T1 and T2 signal intensities and hyperintense blooming on susceptibility-weighted imaging. The lesions reached large sizes exhibiting spherical, cystic, and often "pseudotumoral" morphology. In 3 patients, developmental venous anomalies (DVAs) were found. In 4 of the 5 patients, the CCMs and hematomas were totally removed. All patients had a clinically excellent functional outcome without surgical complication and with complete resolution of their presenting symptoms. CONCLUSIONS: Cerebellar CMs occur in all pediatric age groups and display characteristic clinical and imaging features. In children, CCMs reach large sizes and can result in massive hemorrhage, often leading to a possible diagnosis of hemorrhage into a tumor. An associated DVA is quite common. Surgery is a safe and efficient treatment option with excellent outcomes in patients.

Radiographic Detectability of Retained Neuropatties in a Cadaver Model.

BACKGROUND: Counts are the commonest method used to ensure that all sponges and neuropatties are removed from a surgical site before closure. When the count is not reconciled, plain radiographs of the operative site are taken to determine whether the missing patty has been left in the wound. The purpose of this study was to describe the detectability of commonly used neuropatties in the clinical setting using digital technologies. METHODS: Neuropatties were implanted into the anterior and posterior cranial fossae and the thoracolumbar extradural space of a mature male cadaver. Four neuropatty sizes were used: 3 × 1 in, 2 × ½ in, ½ × ½ in, and » × » in. Neuropatties, with size and location chosen at random, were placed in the surgical sites and anteroposterior/posterior-anterior and lateral radiographs were taken using standard portable digital radiographic equipment. Six clinicians reviewed the digital images for the presence or absence of neuropatties. The readers were not aware of the number and size of the patties that were included in each image. RESULTS: The detectability of neuropatties is dependent on the size of the neuropatty's radiopaque marker and the operative site. Neuropatties measuring 2 × ½ in and 3 × 1 in were detected reliably regardless of the operative site. » × » in neuropatties were poorly detected by neurosurgeons and radiologists in all three operative sites. Readers of various experience and background were similar in their ability to detect neuropatties under these conditions. CONCLUSIONS: Under simulated operating room conditions and using currently available neuropatties and plain radiograph imaging technology, small »-in and ½-in neuropatties are poorly visible/detectable on digital images.

Oxygen carrying microbubbles for enhanced sonodynamic therapy of hypoxic tumours.

Tumour hypoxia represents a major challenge in the effective treatment of solid cancerous tumours using conventional approaches. As oxygen is a key substrate for Photo-/Sono-dynamic Therapy (PDT/SDT), hypoxia is also problematic for the treatment of solid tumours using these techniques. The ability to deliver oxygen to the vicinity of the tumour increases its local partial pressure improving the possibility of ROS generation in PDT/SDT. In this manuscript, we investigate the use of oxygen-loaded, lipid-stabilised microbubbles (MBs), decorated with a Rose Bengal sensitiser, for SDT-based treatment of a pancreatic cancer model (BxPc-3) in vitro and in vivo. We directly compare the effectiveness of the oxygen-loaded MBs with sulphur hexafluoride (SF6)-loaded MBs and reveal a significant improvement in therapeutic efficacy. The combination of oxygen-carrying, ultrasound-responsive MBs, with an ultrasound-responsive therapeutic sensitiser, offers the possibility of delivering and activating the MB-sensitiser conjugate at the tumour site in a non-invasive manner, providing enhanced sonodynamic activation at that site.

Delayed visual loss from optochiasmatic arachnoiditis after resection of craniopharyngioma.

Visual loss following surgery for craniopharyngioma is usually the result of operative injury or tumor recurrence. The authors present the case of a 12-year-old boy who developed progressive visual field constriction 11 years after gross-total resection of a solid and cystic craniopharyngioma. No tumor recurrence was evident on multiple MRI studies, and it was only at surgical exploration that the diagnosis of optochiasmatic arachnoiditis was established. Lysis of the adhesions around the optic nerves and chiasm resulted in substantial and sustained visual improvement.

Disruption of silicone valve housing in a Codman Hakim Precision valve with integrated Siphonguard.

Authors of this report describe 2 patients who had undergone shunt insertion for hydrocephalus and who, at 6 weeks or 9 months after their last revision, presented with symptoms of shunt dysfunction and CSF collections at the valve site. At the ensuing shunt revision in both patients, the silicone housing was fractured and the Siphonguard was disconnected from the Codman Hakim Precision flat-bottom valve. The cause of these failures was not clear since manipulation, bending, and twisting of the valves were not thought to have occurred during implantation. A review of the FDA's Manufacturer and User Facility Device Experience (MAUDE) database revealed 58 cases of silicone housing failure in the Codman Hakim Precision valve with integrated Siphonguard since the year 2000. A single report was found in the databases administered by the Canadian Medical Devices Sentinel Network (CMDSNet). The Codman Hakim Precision valves with integrated Siphonguard are delicate devices that do not withstand the intraoperative handling tolerated by other valves. When these valves are implanted, gentle handling and wide exposures are needed to minimize the risk of valve damage. Valves should be handled according to the manufacturer's instructions. However, in light of this particular pattern of failure, it is recommended that the manufacturer redesign this valve to provide handling tolerance that is characteristic of other valves on the market. The featured cases illustrate the importance of the surgeon's role in postmarket surveillance of medical devices and reporting device failures to the responsible agencies and manufacturers.

Integration of psychoanalytic concepts in the formulation and management of hospitalized psychiatric patients.

Although psychoanalysis and psychodynamic psychotherapy have flourished theoretically and in practice for an increasingly widespread population of patients, the mental health professions have in recent decades experienced a hegemony of managed care, a preoccupation with pharmacological approaches at the expense of psychological approaches, and a predilection for brief symptom-focused, more easily researchable manualized psychotherapies, in spite of literature demonstrating the effective contribution of psychoanalysis and psychodynamic thought to the practice of the mental health professions. In this article a psychiatric inpatient is considered from the point of view of what psychodynamic theory can offer practically to understanding and managing her. It is not suggested that this patient might necessarily benefit from formal psychodynamic psychotherapy, but rather that incorporation of a psychodynamic understanding of her can lead to a more effective management approach, especially regarding dealing with staff reactions to disturbing patients. Consideration of the patient's personality and recognition of the patient's having a comorbid personality disorder appeared important in her management, and have practical implications regarding staff members' understanding of the patient and the consequent identification and handling of transference and countertransference manifestations. Problems that are likely to occur as enactments on the inpatient unit can more readily be anticipated or identified earlier and a consistent staff approach prepared. A psychodynamically informed management approach on the inpatient unit can help to anticipate challenging interpersonal experiences such as enactments. Psychodynamic thought has developed in a manner so as to be applicable in an increasingly wide range of clinical situations, not only in terms of the varieties of patients who are deemed to be able to benefit from psychodynamic treatment per se, but also regarding the clinical venues in which psychodynamic concepts can be usefully applied.

Enhanced vascular permeability is hypothesized to promote inflammation-induced carcinogenesis and tumor development via extravasation of large molecular proteins into the tissue.

We propose that the growth of solid tumors is dependent, in part, on the entry of large molecular blood-borne growth regulators into the tissue and is facilitated by the highly permeable nature of tumor blood vessels. There is abundant evidence that the tumor vasculature is hyperpermeable and tumor growth is dependent on mediators that increase vascular permeability (e.g., VEGF and mast cells). Therefore, the extravasation of plasma proteins into the interstitial space could be an important determinant of tumor growth. Angiogenesis promotes cancer by creating a network of blood vessels that supplies oxygen and nutriment. A highly permeable vasculature could complement this by facilitating the entry of plasma proteins into the tumor space, permitting them to exert effects on growth and survival pathways. Plasma proteins could act directly (on the cancer cells) or indirectly (via the stroma), and could conceivably stimulate cell proliferation, enhance cell survival, promote angiogenesis, and/or provide the cells with essential nutrients. Since increased vascular permeability is a hallmark of inflammation and since chronic inflammation is a forerunner to cancer, we also suggest that the prolonged influx of plasma proteins during chronic inflammation could contribute to the carcinogenic process. Perhaps over time and in sufficient quantity, the extruded plasma proteins and the attendant edema set up a feed-forward cycle that exacerbates the inflammation and potentiates the formation of mutagens and growth regulators. It is tempting to speculate that differences in tumor growth/metastasis and patient outcome are at least partly due to the degree of permeability of the tumor vasculature.

HMC-1 human mast cells synthesize neurotensin (NT) precursor, secrete bioactive NT-like peptide(s) and express NT receptor NTS1.

OBJECTIVE AND DESIGN: To determine if mast cells synthesize the inflammatory peptide, neurotensin (NT), secrete immunoreactive and bioactive NT, and express the NT receptor NTS1. MATERIALS: HMC-1 cells, pleural mast cells from Sprague-Dawley rats, LAD2 mast cells, and human cord blood mast cells were used. TREATMENT: HMC-1 cells were stimulated with NT, C48/80, mastoparan, or PGE(2). For changes in cutaneous vascular permeability, anesthetized rats were injected intravenously with Evans Blue dye and intradermally with saline, NT, histamine, diphenhydramine, and C48/80. METHODS: RT-PCR was used to identify RNA transcripts. Histamine was measured by fluorometric assay. In vivo cutaneous vascular permeability assays, radio-immunoassays for NT, Western blotting for the NT precursor protein and NTS1 protein from HMC-1 cells and tissues from rats were used. Immunohistochemistry was used to identify NT precursor-like proteins in HMC-1 mast cells. RESULTS: HMC-1 cells express mRNAs for NT precursor, PC5A processing enzyme and NTS1 receptor. Human cord blood mast cells and LAD2 mast cells express mRNA transcripts for NT precursor and NTS1. Western blotting showed NT precursor and NTS1 receptor in HMC1. Rat tissues with high numbers of mast cells contained NT precursor proteins. NT-like peptides from HMC-1 displayed NT-like bioactivity. CONCLUSIONS: HMC-1 mast cells synthesize and secrete immunoreactive and bioactive NT-like peptide(s) and express the NT receptor, suggesting that NT from mast cells might serve autocrine and paracrine roles.

Endoscopic choroid plexus cauterization versus ventriculoperitoneal shunt for hydranencephaly and near hydranencephaly: a prospective study.

OBJECTIVE: To prospectively evaluate the results of endoscopic choroid plexus cauterization (ECPC) and ventriculoperitoneal shunts (VPSs) in infants with hydranencephaly or near hydranencephaly. METHODS: We prospectively collected clinical data from all untreated hydranencephalic and near hydranencephalic children from October 2006 to March 2008. All patients treated were randomly divided into 2 groups, ECPC or VPS, and submitted to either endoscopic choroid plexus cauterization or ventriculoperitoneal shunt placement. RESULTS: Seventeen patients were entered into the study. ECPC was completed in 9 patients; the procedure successfully controlled excessive head circumference and signs of increased intracranial pressure in 8 of these patients (88.8%). One endoscopic procedure in a hydranencephalic child failed after 7 months, resulting in VPS placement. Thus, of the 10 patients randomized to ECPC, 8 were treated successfully by ECPC (80%), and 2 went on to have a VPS. There were no complications related to this method of treatment. Seven children were randomized to the VPS group; and of these, 2 patients (28.5%) required shunt revisions during follow-up. There were no complications related to shunt placement. There was no difference in the success rate between patients randomized to ECPC and VPS, but the ECPC was more economical. CONCLUSION: ECPC is an acceptable alternative to VPS for treatment of hydranencephaly and near hydranencephaly. It is a single, definitive, safe, effective, and economical treatment that may avoid the complications of shunting.

Bilateral choroid plexus hyperplasia: a case report and management strategies.

INTRODUCTION: Choroid plexus hyperplasia (CPH) is a rare cause of cerebrospinal fluid (CSF) overproduction and shunt-resistant hydrocephalus in infants. If treated with a ventriculoperitoneal (VP) shunt, these patients secondarily develop CSF accumulation along the shunt tract and within the peritoneum. The surgical management of this condition is not as clearly defined as in the case of a choroid plexus papilloma or carcinoma. CASE REPORT: An 8-day-old male patient presented with bulging fontanelle, head circumference = 42 cm (>98th percentile), and cranial ultrasound demonstrating communicating hydrocephalus with enlarged choroid plexuses. A VP shunt was inserted, and secondarily progressive hydrocephalus, shunt tract fluid accumulation, and ascites developed. The infant underwent staged bilateral plexectomy and is tolerating CSF diversion. The pathology confirmed CPH. DISCUSSION: Of the cases reported in the literature, treatments have included CSF shunting, endoscopic coagulation, and craniotomy with plexectomy. CSF shunting was required in the majority but not all. Only those having undergone bilateral choroid plexectomy have been rendered shunt free.

Formulating a web-based educational needs assessment questionnaire from healthcare competencies.

This paper by David Cochrane, Janette Palmer, Grace Lindsay, Elizabeth Tolmie, Douglas Allan and Kay Currie describes a project that led to the formulation of an online educational needs assessment tool by drawing on national healthcare competencies in coronary heart disease. It discusses the merits of web-based data collection and concludes that web-based survey systems offer distinct advantages providing researchers proceed with care.

Optic nerve sheath fenestration and bilateral expansile cranioplasty for raised intracranial pressure in craniometaphyseal dysplasia: a case report.

INTRODUCTION: Raised intracranial pressure (ICP) has been previously associated with craniometaphyseal dysplasia (CMD). To our knowledge, expansile cranioplasty has not previously been described as a treatment for raised ICP in this setting. We describe our evaluation and surgical management of a patient presenting with seizures, headaches, and CMD. CASE REPORT: An 18-year-old male presented with seizures, headaches, and diminished visual acuity, and was found to have chronic bilateral papilledema. Lumbar puncture demonstrated raised opening pressure (50 cm of water). Plain skeletal radiographs revealed long-bone dysplasia, and computed tomography (CT) of the head demonstrated diffuse thickening of the calvarium, diminished subarachnoid spaces, and slit ventricles. The raised ICP was managed with bilateral fronto-parieto-temporal expansile cranioplasty and right optic nerve sheath fenestration. At 6 months follow-up, the headaches and papilledema completely resolved. The visual acuity improved as did the seizure control. Follow-up CT demonstrated the normalization of the subarachnoid spaces and ventricles. CONCLUSION: Expansile cranioplasty, in conjunction with optic nerve sheath fenestration, may represent a safe and effective treatment for raised ICP associated with CMD.

Nitric oxide inhibits metamorphosis in larvae of Crepidula fornicata, the slippershell snail.

This paper concerns the role of nitric oxide (NO) in controlling metamorphosis in the marine gastropod Crepidula fornicata. Metamorphosis was stimulated by the nitric oxide synthase (NOS) inhibitors AGH (aminoguanidine hemisulfate) and SMIS (S-methylisothiourea sulfate) at concentrations of about 100-1000 micromol l(-1) and 50-200 micromol l(-1), respectively. Metamorphosis was not, however, induced by the NOS inhibitor l-NAME (l-N(G)-nitroarginine methyl ester) at even the highest concentration tested, 500 micromol l(-1). Moreover, pre-incubation with l-NAME at 20 and 80 micromol l(-1) did not increase the sensitivity of competent larvae to excess K(+), a potent inducer of metamorphosis in this species; we suggest that either l-NAME is ineffective in suppressing NO production in larvae of C. fornicata, or that it works only on the constitutive isoform of the enzyme. In contrast, metamorphosis was potentiated by the guanylate cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3, -a]quinoxalin-1-one) in response to a natural metamorphic inducer derived from conspecific adults. Because NO typically stimulates cGMP production through the activation of soluble guanylate cyclase, this result supports the hypothesis that NO acts as an endogenous inhibitor of metamorphosis in C. fornicata. The expression of NOS, shown by immunohistochemical techniques, was detected in the apical ganglion of young larvae but not in older larvae, further supporting the hypothesis that metamorphosis in C. fornicata is made possible by declines in the endogenous concentration of NO during development.

Regulation of neurotensin receptor function by the arachidonic acid-lipoxygenase pathway in prostate cancer PC3 cells.

Neurotensin (NT) elevates leukotriene levels in animals and stimulates 5-HETE formation in prostate cancer PC3 cells. PC3 cell growth is stimulated by NT and inhibited by lipoxygenase (LOX) blockers. This led us to test LOX blockers (NDGA, MK886, ETYA, Rev5901, AA861 and others) for effects on NT binding and signaling. LOX blockers dramatically enhanced 125I-neurotensin binding to NT receptor NTR1 in PC3 cells, whereas they inhibited NT-induced inositol phosphate formation. These effects were indirect (binding to isolated membranes was unaffected), receptor-specific (binding to beta2-adrenergic, V1a-vasopressin, EGF and bombesin receptor was unaffected) and pathway-specific (cyclooxygenase inhibitors were inactive). NT receptor affinity was increased but receptor number and % internalization were unchanged. Also supporting the involvement of arachidonic acid metabolism in NTR1 regulation was the finding that inhibitors of PLA2 and DAG lipase enhanced NT binding. These findings suggest that NTR1 is regulated by specific feedback mechanism(s) involving lipid peroxidation and/or LOX-dependent processes.