Transseptal puncture in the dog utilizing three-dimensional transesophageal echocardiographic guidance.

Transseptal puncture is necessary to access the left atrium and mitral valve from a transvenous approach but is poorly described in veterinary medicine. The procedure is generally regarded as difficult and dangerous, particularly given the size of most small animal patients. Precise imaging is paramount to the procedure to ensure that puncture occurs within the desired location and to monitor for potential complications. Transesophageal echocardiography, including biplanar two-dimensional and particularly three-dimensional modalities, has great potential to improve the success and safety of transseptal puncture due to superior visualization of the fossa ovalis and other intracardiac structures. Here, we describe the use of transesophageal echocardiography to guide transseptal puncture based on our experience in 159 dogs, with an emphasis on three-dimensional echocardiography. We also detail how to perform transseptal puncture from a jugular approach, which we consider preferable in most patients. Complications from transseptal puncture are discussed, along with ways to limit those complications.

Outcomes of Preoperative Transophthalmic Artery Embolization of Meningiomas: A Systematic Review with a Focus on Embolization Agent.

BACKGROUND: Transophthalmic artery embolization of intracranial meningiomas is thought to be associated with a high complication risk. PURPOSE: With advances in endovascular techniques, we systematically reviewed the current literature to improve our understanding of the safety and efficacy of transophthalmic artery embolization of intracranial meningiomas. DATA SOURCES: We performed a systematic search using PubMed from inception until August 3, 2022. STUDY SELECTION: Twelve studies with 28 patients with intracranial meningiomas embolized through the transophthalmic artery were included. DATA ANALYSIS: Baseline and technical characteristics and clinical and safety outcomes were collected. No statistical analysis was conducted. DATA SYNTHESIS: The average age of 27 patients was 49.5 (SD, 13) years. Eighteen (69%) meningiomas were located in the anterior cranial fossa, and 8 (31%), in the sphenoid ridge/wing. Polyvinyl alcohol particles were most commonly (n = 8, 31%) used to preoperatively embolize meningiomas, followed by n-BCA in 6 (23%), Onyx in 6 (23%), Gelfoam in 5 (19%), and coils in 1 patient (4%). Complete embolization of the target meningioma feeders was reported in 8 (47%) of 17 patients; partial embolization, in 6 (32%); and suboptimal embolization, in 3 (18%). The endovascular complication rate was 16% (4 of 25), which included visual impairment in 3 (12%) patients. LIMITATIONS: Selection and publication biases were limitations. CONCLUSIONS: Transophthalmic artery embolization of intracranial meningiomas is feasible but is associated with a non-negligible complication rate.

Post-traumatic stress symptoms in childhood brain tumour survivors and their parents.

OBJECTIVES: This study aimed to investigate post-traumatic stress symptoms (PTSS) in childhood brain tumour survivors and their parents. A further aim was to explore the relationship between objective illness parameters, parent-child interactions, coping styles and PTSS. METHODS: A cross-sectional correlational design was employed. Fifty-two childhood brain tumour survivors, aged 8-16, and 52 parents completed a battery of questionnaires designed to assess quality of parent-child interactions, monitoring and blunting attentional coping styles and PTSS. RESULTS: Over one-third (35%) of survivors and 29% of their parents reported severe levels of PTSS (suggestive of post-traumatic stress disorder 'caseness'). Increased parent-child conflict resolution for survivors and number of tumour recurrences for parents independently predicted the variance in PTSS. CONCLUSIONS: For a substantial proportion of brain tumour survivors and their parents the process of survivorship is a considerably distressing experience.

Should Robotic Surgery Simulation Be Introduced in the Core Surgical Training Curriculum?

Introduction: The focus of this research is to qualitatively analyse the literature and address the knowledge gap between robotic surgery simulation (RoSS) and core surgical training curriculum. It will compare the effectiveness and the benefits of using robotic simulators in training as compared to the current standard training methods. Materials and Methods: A qualitative research of literature was carried out with the use of critical analysis formatting to expand the search. The inclusion criteria entailed selecting academic resources that focused on Robotic Surgery Simulation (RoSS) and core surgical curriculum. The Online databases used in the search took into account information retrieval from stakeholders. Evidence Synthesis: In this article, we compiled and scrutinized the available relevant literature comparing performance assessments, surgical skills transfer and assessment tools between robotic surgery simulation (RoSS) and current training platforms in open and minimal access surgery. Data that has been published underpins the authenticity of robotic Surgery Simulation (RoSS), based on a combination of observational evaluation and simulation scores. Conclusion: The introduction of robotic surgery simulation (RoSS) has the potential to bring major improvements in the surgical training curriculum. RoSS platforms are more robust in terms of ensuring rapid surgical skills transfer/ acquisition, assessment is standardized, unbiased and the training covers non-technical skills aspects.

Astrocytoma derived short-term cell cultures retain molecular signatures characteristic of the tumour in situ.

The heterogeneity of tumours and uncertainties surrounding derived short-term cell cultures and established cell lines fundamentally challenge the research and understanding of tumour growth and development. When tumour cells are cultured, changes are inevitably induced due to the artificial growth conditions. Several recent studies have questioned how representative established cell lines or derived short-term cell cultures are of the tumour in situ. We have characterised gene expression changes induced by short-term culture in astrocytoma in order to determine whether derived short-term cell cultures are representative of the tumour in situ. In comparison to the majority of studies, paired biopsies and derived short-term cultures were investigated to reduce the effects of long-term culture and inter-tumour variability when comparing biopsies and derived cultures from tumours with the same histology from different individuals. We have used the Affymetrix GeneChip U133A to generate gene expression profiles of 6 paediatric pilocytic astrocytoma (PA) biopsies and derived short-term cell cultures and 3 adult glioblastoma multiforme (GBM) biopsies and derived short-term cultures. Significant differential gene expression is induced by short-term culture. However, when the biopsy and derived short-term cell culture samples were grouped according to tumour type (PA and GBM) a molecular signature of 608 genes showed significant differential expression between the groups. This gene cohort can distinguish PA and GBM tumours, regardless of the sample source, suggesting that astrocytoma derived short-term cultures do retain key aspects of the global tumour expression profile and are representative of the tumour in situ. Furthermore, these genes are involved in pathways and functions characteristic of adult GBM including VEGF signalling, hypoxia and TP53 signalling.

Boron modifications produced in an induction-coupled argon plasma.

Most of the small particles (50 to 100 micrometers in diameter) of microcrystalline beta-rhombohedral boron that quickly transit an argon plasma maintained within a radio-frequency induction-coupled torch emerge as better crystallized spheroids of the same crystalline form and nearly the same size as the starting material. A few crystals of each of four distinctive, well-faceted habits are formed along with the general product. Three of these types are monocrystals of the beta-rhombohedral polymorph, of the tetragonal-III modification, and of an unreported cubic form of boron. Specimens of the fourth type are polycrystals of another unreported form of boron, apparently consisting of many hexagonal platelets stacked in an imprecise fashion.

Is CSF cytology a useful diagnostic procedure in staging paediatric CNS tumours?

OBJECTIVES: To evaluate whether there are any factors that predict malignant cells being found in paediatric cerebrospinal fluid (CSF) samples. To determine whether CSF provides useful staging information not provided by magnetic resonance imaging (MRI) in paediatric patients with primary central nervous system (CNS) malignancy. METHODS: We compared the CSF cytology and spinal MRI staging results in paediatric patients with primary CNS malignancy at a UK tertiary referral centre, over a decade. RESULTS: Of 159 CSF samples, 72 samples were from 72 patients with primary CNS malignancy with spinal MRI available for comparison. Eight of these 72 had positive cytology (seven malignant and one suspicious). All had a high clinical suspicion of tumour at the time of sampling. Of the 72 patients, only two had evidence of CSF spread on MRI spinal staging and CSF cytology; ten had MRI without cytological evidence and six had cytological without MRI evidence. CONCLUSIONS: In paediatric patients with primary CNS tumours, CSF cytology provides useful staging information. Spinal MRI alone may miss some patients with CSF spread who would be identified with CSF cytology.

Predictors of the need for an extracervical approach to intrathoracic goitre.

Background: Sternotomy and lateral thoracotomy are required infrequently to remove an intrathoracic goitre (ITG). As few studies have explored the need for an extracervical approach (ECA), the aim of this study was to examine this in a large cohort of patients. Methods: A prospective database of all patients who had surgery for ITG between 2004 and 2016 was interrogated. Patient demographics, preoperative characteristics and type of operation were analysed to identify factors associated with an ECA. Results: Of 237 patients who had surgery for ITG, 29 (12·2 per cent) required an ECA. ITGs below the aortic arch (odds ratio (OR) 10·84; P = 0·004), those with an iceberg shape (OR 59·30; P < 0·001) and revisional surgery (OR 4·83; P = 0·022) were significant preoperative predictors of an ECA. Conclusion: The extent of intrathoracic extension in relation to the aortic arch, iceberg goitre shape and revisional surgery were independent risk factors for ECA. Careful preoperative assessment should take these factors into consideration when determining the optimal surgical approach to ITG.

Evidence of Early Emergence of the Primary Dentition in a Northern Plains American Indian Population.

The purposes of this study were to describe primary tooth emergence in an American Indian (AI) population during the first 36 mo of life to compare 1) patterns of emergence between male and female children and 2) tooth emergence between these AI children and other U.S. ethnic groups. Data were derived from a birth cohort of 239 AI children from a Northern Plains tribe participating in a longitudinal study of early childhood caries, with examination data at target ages of 8, 12, 16, 22, 28, and 36 mo of age (±1 mo). Patterns of emergence in AI children were characterized and sex comparisons accomplished with interval-censored survival methodology. Numbers of erupted teeth in AI children at each age were compared via Kruskal-Wallis tests against those in children of the same age, as drawn from a cross-sectional study of dental caries patterns in Arizona; these comparisons were based on the dental examinations of 547 White non-Hispanic and 677 Hispanic children. Characterization of time to achievement of various milestones-including emergence of the anterior teeth, the first molars, and the complete primary dentition-provided no evidence of sex differences among AI children. AI children had significantly more teeth present at 8 mo (median, 3) than either White non-Hispanic (P < 0.0063) or Hispanic (P < 0.0001) children (median, 2 each). This was also true at 12 mo (P < 0.001; medians, 8 vs. 6 and 7, respectively) and 16 mo (P < 0.001; medians, 12 vs. 11 each). Less pronounced differences were seen at 22 mo (P < 0.0001). White non-Hispanic and Hispanic children did not differ at any time considered (P > 0.05). These results provide evidence of earlier tooth emergence in AI children than in the other 2 ethnicities. Although the underlying etiology of the severity of early childhood caries in AI children is likely to be multifactorial, earlier tooth emergence may be a contributing factor. Knowledge Transfer Statement: The findings of this study have practical implications for practitioners providing childhood oral health care to ethnic groups with early tooth emergence. It may be important to provide parents with information on toothbrushing, dentist visits, and other practices supportive of good oral health as early as possible to protect their children's primary dentition.

Longitudinal study of bone density and periodontal disease in men.

Bone loss is a feature of both periodontitis and osteoporosis, and periodontal destruction may be influenced by systemic bone loss. This study evaluated the association between periodontal disease and bone mineral density (BMD) in a cohort of 1347 (137 edentulous) older men followed for an average of 2.7 years. Participants were recruited from the Osteoporotic Fractures in Men Study. Random half-mouth dental measures included clinical attachment loss (CAL), pocket depth (PD), calculus, plaque, and bleeding. BMD was measured at the hip, spine, and whole-body, by dual-energy x-ray absorptiometry, and at the heel by ultrasound. After adjustment for age, smoking, race, education, body mass index, and calculus, there was no association between number of teeth, periodontitis, periodontal disease progression, and either BMD or annualized rate of BMD change. We found little evidence of an association between periodontitis and skeletal BMD among older men.

Phase I trial of orally administered pentosan polysulfate in patients with advanced cancer.

Tumor angiogenesis is critically important to tumor growth and metastasis. We have shown that pentosan polysulfate (PPS) is an effective inhibitor of heparin-binding growth factors in vitro and can effectively inhibit the establishment and growth of tumors in nude mice. Following completion of our Phase I trial of s.c. administered PPS, we performed a Phase I trial of p.o. administered PPS in patients with advanced cancer to determine the maximum tolerated dose (MTD) and toxicity profile and to search for any evidence for biological activity in vivo. Patients diagnosed with advanced, incurable malignancies who met standard Phase I criteria and who did not have a history of bleeding complications were enrolled, in cohorts of three, to receive PPS p.o. t.i.d., at planned doses of 180, 270, 400, 600, and 800 mg/m2. Patients were monitored at least every 2 weeks with physical exams and weekly with hematological, chemistry, stool hemoccult, and coagulation blood studies, and serum and urine samples for PPS and basic fibroblastic growth factor (bFGF) levels were also taken. The PPS dose was escalated in an attempt to reach the MTD. Eight additional patients were enrolled at the highest dose to further characterize the toxicity profile and biological in vivo effects of PPS. A total of 21 patients were enrolled in the three cohorts of doses 180 (n = 4), 270 (n = 3), and 400 (n = 14) mg/m2. The most severe toxicities seen were grade 3 proctitis and grade 4 diarrhea; however, 20 of the 21 patients had evidence of grade 1 or 2 gastrointestinal (GI) bleeding. These toxicities became evident at a much earlier time point as the dose was increased, but their severities were similar at all dose levels. There were no objective responses, although three patients had prolonged stabilization of previously progressing disease. Pharmacokinetic analysis suggested marked accumulation of PPS upon chronic administration. Serum and urine bFGF levels failed to show a consistent, interpretable pattern; however the data suggested an inverse relationship between PPS and bFGF levels in vivo. A MTD could not be determined using the daily t.i.d. dosing schedule due to the development of grade 3/4 GI toxicity (proctitis) at all dose levels studied. PPS, administered p.o. at doses of 400 mg/m2 t.i.d., did not cause significant systemic toxicity, but most patients developed moderate-to-severe GI toxicity within 1-2 months. The cause of the GI toxicity was unclear, but it was readily reversible upon cessation of the agent. The suggestion of an inverse relationship between PPS and bFGF supports further study of PPS as an antiangiogenic agent. The tested doses and schedule cannot be recommended for further study. Subsequent murine experiments showed PPS to be more effective as an anticancer agent when it is given intermittently. We propose a study of PPS given on a weekly schedule in further clinical trials.

A Phase I and pharmacokinetic study of TNP-470 administered weekly to patients with advanced cancer.

A Phase I study of angiogenesis inhibitor TNP-470 was conducted in patients with advanced cancer. TNP-470 (25-235 mg/m2) was administered i.v. over 4 h once a week to patients who had solid tumors refractory to the best available treatment or with a high risk of recurrence and who had normal renal, hepatic, and hematological function and no evidence of coagulopathy. The aims of the study were to determine the maximum tolerated dose, dose-limiting toxicities (DLTs), and the pharmacokinetics of TNP-470 given on a once-weekly schedule. Thirty-six patients, ages 23-75 (median, 54 years), with an Eastern Cooperative Oncology Group performance status of 0-2 were treated. The number of patients at each dose level (mg/m2) were 6 (25), 3 (50), 3 (75), 3 (100), 3 (133), 12 (177), and 6 (235). The principal toxicities of TNP-470 were dizziness, lightheadedness, vertigo, ataxia, decrease in concentration and short-term memory, confusion, anxiety, and depression, which occurred at doses of 133, 177, and 235 mg/m2. Two patients treated at 235 mg/m2 experienced DLT in the form of grade III cerebellar neurotoxicity after 6 weeks of treatment. Overall, these neurological symptoms were dose-related, had an insidious onset, progressively worsened with treatment, and resolved completely within 2 weeks of stopping the drug. One patient with malignant melanoma had stabilization of the previously growing disease for 27 weeks while on the treatment. Two patients, one with adenocarcinoma of the colon and the other with a soft tissue sarcoma, had no clinically detectable disease but were at high risk for recurrence at the initiation of treatment and received 13 months and > 3 years of treatment, respectively, with no evidence of disease recurrence. The remaining patients had progression of their disease after 1-6 months of treatment. The mean plasma half-life (t(1/2)) of TNP-470 and its principal metabolite, AGM-1883, were extremely short (harmonic mean, t(1/2) of 2 and 6 min, respectively) with practically no drug detectable in the plasma by 60 min after the end of the infusion. MII, an inactive metabolite, had a considerably longer t(1/2) of approximately 2.6 h. Mean peak TNP-470 concentrations were > or = 400 ng/ml at doses > or = 177 mg/m2. On the basis of this study, the maximum tolerated dose of TNP-470 administered on a weekly schedule was 177 mg/m2 given i.v over 4 h. The principal DLT was neurotoxicity, which appeared to be dose-related and was completely reversible. On the basis of the short plasma t(1/2) of TNP-470, exploration of a prolonged i.v. infusion schedule is warranted.

Tricalcium-phosphate and hydroxyapatite bone-graft extender for use in impaction grafting revision surgery. An in vitro study on human femora.

Impacted morsellised allografts have been used successfully to address the problem of poor bone stock in revision surgery. However, there are concerns about the transmission of pathogens, the high cost and the shortage of supply of donor bone. Bone-graft extenders, such as tricalcium phosphate (TCP) and hydroxyapatite (HA), have been developed to minimise the use of donor bone. In a human cadaver model we have evaluated the surgical and mechanical feasibility of a TCP/HA bone-graft extender during impaction grafting revision surgery. A TCP/HA allograft mix increased the risk of producing a fissure in the femur during the impaction procedure, but provided a higher initial mechanical stability when compared with bone graft alone. The implications of the use of this type of graft extender in impaction grafting revision surgery are discussed.

Stabilizing Dog Populations and Improving Animal and Public Health Through a Participatory Approach in Indigenous Communities.

Free-roaming dog populations are a global concern for animal and human health including transmission of infectious disease (e.g. rabies, distemper and parasites), dog bite injuries/mortalities, animal welfare and adverse effects on wildlife. In Saskatchewan (SK), Canada, veterinary care is difficult to access in the remote and sparsely inhabited northern half of the province, where the population is predominately Indigenous. Even where veterinary clinics are readily available, there are important barriers such as cost, lack of transportation, unique cultural perspectives on dog husbandry and perceived need for veterinary care. We report the effects of introducing a community action plan designed to improve animal and human health, increase animal health literacy and benefit community well-being in two Indigenous communities where a dog-related child fatality recently occurred. Initial door-to-door dog demographic surveys indicated that most dogs were sexually intact (92% of 382 dogs), and few had ever been vaccinated (6%) or dewormed (6%). Approximately three animal-related injuries requiring medical care were reported in the communities per 1000 persons per year (95% CL: 1.6-6.6), and approximately 86% of 145 environmentally collected dog faecal samples contained parasites, far above levels reported in other urban or rural settings in SK. Following two subsidized spay/neuter clinics and active rehoming of dogs, parasite levels in dog faeces decreased significantly (P < 0.001), and important changes were observed in the dog demographic profile. This project demonstrates the importance of engaging people using familiar, local resources and taking a community specific approach. As well, it highlights the value of integrated, cross-jurisdictional cooperation, utilizing the resources of university researchers, veterinary personnel, public health, environmental health and community-based advocates to work together to solve complex issues in One Health. On-going surveillance on dog bites, parasite levels and dog demographics are needed to measure the long-term sustainability of benefits to dog, human and wildlife health.

Growth hormone treatment of children with brain tumors and risk of tumor recurrence.

GH is increasingly used for treatment of children and adults. It is mitogenic, however, and there is therefore concern about its safety, especially when used to treat cancer patients who have become GH deficient after cranial radiotherapy. We followed 180 children with brain tumors attending three large hospitals in the United Kingdom and treated with GH during 1965-1996, and 891 children with brain tumors at these hospitals who received radiotherapy but not GH. Thirty-five first recurrences occurred in the GH-treated children and 434 in the untreated children. The relative risk of first recurrence in GH-treated compared with untreated patients, adjusted for potentially confounding prognostic variables, was decreased (0. 6; 95% confidence interval, 0.4-0.9) as was the relative risk of mortality (0.5; 95% confidence interval, 0.3-0.8). There was no significant trend in relative risk of recurrence with cumulative time for which GH treatment had been given or with time elapsed since this treatment started. The relative risk of mortality increased significantly with time since first GH treatment. The results, based on much larger numbers than previous studies, suggest that GH does not increase the risk of recurrence of childhood brain tumors, although the rising trend in mortality relative risks with longer follow-up indicates the need for continued surveillance.

Water-borne fluoride and cortical bone mass: a comparison of two communities.

This study investigated the relationship between cortical bone mass in an older female population and their ingestion of fluoride from community water supplies. The study was conducted among lifelong female residents in Lordsburg (3.5 ppm fluoride) and Deming (0.7 ppm fluoride), NM. A total of 151 postmenopausal women ranging in age from 39 to 87 years took part; 69 were residents of the optimal-fluoride community, while the remaining 82 were residents of the high-fluoride community. Although bivariate analyses showed no difference in cortical bone mass between women in the two communities, with multiple regression analyses, significant predictors of bone mass (p less than 0.05) were weight, years since menopause, current estrogen supplementation, diabetes, and fluoride exposure status. Based on a model containing all of these variables, women living in the high-fluoride community had a bone mass ranging from 0.004 to 0.039 g/cm2 less than that of similar women living in the optimum-fluoride community. These results suggest that lifelong ingestion of water containing 3.5 ppm fluoride, compared with water containing 0.7 ppm fluoride, does not increase cortical bone mass in women of similar age, weight, and menopausal status. Under the conditions of this study, cortical bone mass might be reduced in a high-fluoride area.

The association between water-borne fluoride and bone mineral density in older adults.

While the benefit of fluoridation in the prevention of dental caries has been overwhelmingly substantiated, the effect of fluoride on bone mineral density is less clear. This cross-sectional study was designed to compare the bone mineral densities of older adults exposed to various levels of fluoride from community water systems. Participants were recruited from 3 rural communities with naturally occurring fluoride in their water systems at 0.03, 0.7, and 2.5 mg/L. All adults, age 60 and over, were eligible if they were ambulatory and had a long-term history (> or = 20 yrs) of ingesting city water. Bone mineral density (BMD) was measured by means of dual-energy x-ray absorptiometry at 3 anatomical sites: lumbar spine, proximal femur, and forearm. A total of 353 white non-Hispanic women and 317 white non-Hispanic men took part in the study. When the data were stratified by city of residence and gender, men and women living in the community with high levels of fluoride in their community water system had significantly higher lumbar spine BMD than their counterparts from the communities with low and moderate fluoride levels. The women in the high-fluoride community had significantly higher proximal femur BMD, but there were no statistically significant differences among men in either proximal femur or forearm BMD. Long-term exposure (> or = 20 yrs) to higher levels of fluoride appears to have a positive impact on lumbar spine and proximal femur BMD. Based on the results of this study, exposure to fluoride at levels considered "optimal" for the prevention of dental caries (from 0.7 to 1.2 mg/L) appears to have no significant impact on bone mineral density. The relationship between higher levels of fluoride exposure and bone mineral density requires further investigation.

Medulloblastoma: is the 5-year survival rate improving? A review of 80 cases from a single institution.

A series of 80 cases of medulloblastomas in children undergoing operation and postoperatively followed between 1980 and 1990 at Great Ormond Street Hospital for Children (GOSH) has been reviewed and compared to an earlier series reported from the same institution by McIntosh. The overall 5-year survival rate for the present series was 50%, although three patients died after surviving 5 years. The operative mortality rate was 5%. Survival analysis revealed that the presence or absence of spinal metastases and the necessity for some form of cerebrospinal fluid diversion within 30 days of the operation independently significantly affected survival in this series. Those patients with no spinal metastasis and total tumor removal had a 5-year survival rate of 73%, making this the most favorable subgroup in the series. Patient age and gender, duration of symptoms, Chang T stages, tumor volume, extent of resection, and postoperative chemotherapy were not significant variables. Although these results are better than those reported in the earlier GOSH series, they are not significantly different from the results of the second 5-year cohort of patients described in that article. Radiotherapy remains the greatest advance in treatment, although it is hoped that further improvement will result from the various chemotherapy protocols now being studied and from increasing knowledge of the biological behavior of these tumors.

Surveillance neuroimaging in childhood intracranial ependymoma: how effective, how often, and for how long?

OBJECT: The authors examined images obtained in 52 children with intracranial ependymomas to determine risk factors for tumor recurrence and to assess the impact of surveillance imaging on patient outcome. METHODS: Data obtained in all children with intracranial ependymomas were prospectively entered into a database from January 1987 to June 2000. The imaging and clinical details in all patients were reviewed. Fifty-two children with histologically proven intracranial ependymomas were treated at the authors' institution; recurrences developed in 28 (54%) of them, with a median time from surgery to first recurrence of 14.5 months (range 3-65 months). Of these tumor recurrences, 43% were asymptomatic and were noted on surveillance imaging. Seventeen children died, all of whom had recurrences. Incomplete excision of the primary tumor was significantly associated with reduced time to recurrence (p = 0.0144) and time to death (p = 0.0472). The age of the patient, location of the primary tumor, histological findings, and the presence or absence of spinal metastases on preoperative imaging were not significantly associated with outcome. The risk of death at any given time was 12-fold greater in patients in whom a recurrence was identified due to symptoms rather than on surveillance images (p = 0.016). CONCLUSIONS: Recurrent childhood ependymoma has a poor prognosis. The extent of the initial local tumor resection is the factor most closely associated with outcome. Surveillance imaging reveals a substantial number of asymptomatic recurrences, and survival appears to be improved in these patients compared with those identified by symptoms. The improvement in survival is thought to be greater than that expected just from earlier diagnosis.

Fluoride and bone health.

This paper reviews some of the studies related to the effect of fluoride on the skeletal system of humans and outlines the knowns and unknowns of fluoride and bone health. Current research indicates that, in large enough doses, fluoride stimulates bone formation by osteoblastic stimulation, increases bone formation earlier and to a larger extent in trabecular bone compared to cortical bone, and increases spinal bone density. There is controversy, however, concerning the efficacy of fluoride as a therapeutic agent in the treatment of osteoporosis. Some clinical studies have found a reduction in vertebral fracture rates while others have not. To date, only ecologic studies have been conducted on the association between water fluoridation and hip fractures. The inability of ecologic studies to control for confounding variables makes their interpretation difficult. Based on the literature presented, it is concluded that there are more unknowns than knowns in terms of fluoride's effect on bone, osteoporosis, and fractures. One of the major unknowns in the relationship between fluoride and bone health is dose and duration. Two studies are underway that attempt to describe the dose-response relationship between waterborne fluoride and osteoporosis. These studies will be completed in the near future and their results, while providing new insight into fluoride's effects on bone, will by no means answer all the questions raised on this issue.