Clinical and technical factors in endoscopic skull base surgery associated with reconstructive success.

BACKGROUND: In this study, we identified key discrete clinical and technical factors that may correlate with primary reconstructive success in endoscopic skull base surgery (ESBS). METHODS: ESBS cases with intraoperative cerebrospinal fluid (CSF) leaks at four tertiary academic rhinology programs were retrospectively reviewed. Logistic regression identified factors associated with surgical outcomes by defect subsite (anterior cranial fossa [ACF], suprasellar [SS], purely sellar, posterior cranial fossa [PCF]). RESULTS: Of 706 patients (50.4% female), 61.9% had pituitary adenomas, 73.4% had sellar or SS defects, and 20.5% had high-flow intraoperative CSF leaks. The postoperative CSF leak rate was 7.8%. Larger defect size predicted ACF postoperative leaks; use of rigid reconstruction and older age protected against sellar postoperative leaks; and use of dural sealants compared to fibrin glue protected against PCF postoperative leaks. SS postoperative leaks occurred less frequently with the use of dural onlay. Body-mass index, intraoperative CSF leak flow rate, and the use of lumbar drain were not significantly associated with postoperative CSF leak. Meningitis was associated with larger tumors in ACF defects, nondissolvable nasal packing in SS defects, and high-flow intraoperative leaks in PCF defects. Sinus infections were more common in sellar defects with synthetic grafts and nondissolvable nasal packing. CONCLUSIONS: Depending on defect subsite, reconstructive success following ESBS may be influenced by factors, such as age, defect size, and the use of rigid reconstruction, dural onlay, and tissue sealants.

Review and action plan for oral health improvement in Sheffield special schools.

A description of the process of a review of oral health improvement in special schools in Sheffield and the implementation of an action plan for these activities. Public health competencies encompassed: assessing the evidence on oral health and dental interventions, programmes and services; strategic leadership and collaborative working for health; oral health improvement.

NHS dental professionals' evaluation of a child protection learning resource.

The aim of this survey was to evaluate the impact of an educational child protection resource which had been developed and made available, free of charge, to all NHS dental practices and salaried primary dental care services in England and concurrently published online. A postal questionnaire was sent to a random sample of 1000 NHS dental practices to assess whether the learning objectives of the educational resource had been met. A total of 467 questionnaires were completed (46.7% response rate). Almost two thirds of participants (63.4%) remembered receiving the Child Protection and Dental Team (CPDT) handbook or seeing the website and almost all of them had used (looked at or read) it and felt able to access it if needed. Of the 265 users, 76.2% felt it had improved their knowledge of child protection, 60.5% had adopted a child protection policy, 53.7% had identified a child protection lead and 25.8% had arranged further training as a result of using the educational resource. The findings from the evaluation indicated that the learning objectives of the CPDT educational resource had been met and highlighted ways in which the resource could be further improved to effectively meet the needs of dental professionals.

Safeguarding children in dentistry: 2. Do paediatric dentists neglect child dental neglect?

In this second part of a two-part report, further findings of a postal questionnaire sent in March 2005 to dentists with an interest in paediatric dentistry working in varied UK settings are presented and discussed in the context of current multi-agency good practice in safeguarding and promoting the welfare of children. Using insights gained from a survey of self-reported management of children with neglected dentitions, this paper explores whether paediatric dentists neglect child dental neglect. The authors conclude that current practice already includes much that contributes to promoting children's oral health and wellbeing. However, in a society where children continue to suffer as a result of abuse and neglect, they warn that improvements are needed in communication between dentists and other health and social care professionals if children's welfare is to be safeguarded and promoted effectively and future tragedies avoided.

Safeguarding children in dentistry: 1. Child protection training, experience and practice of dental professionals with an interest in paediatric dentistry.

Following several highly publicised inquiries into the deaths of children from abuse and neglect, there has been much recent interest in the role and responsibility of all health professionals to protect children at risk of maltreatment. The findings of a postal questionnaire, sent in March 2005 to 789 dentists and dental care professionals with an interest in paediatric dentistry working in varied settings in the UK, are presented in a two-part report and discussed in the context of current multi-agency good practice in safeguarding and promoting the welfare of children. This first part explores reported child protection training, experience and practice. There was a significant gap between recognising signs of abuse and responding effectively: 67% of respondents had suspected abuse or neglect of a child patient at some time in their career but only 29% had ever made a child protection referral. The dental profession is alerted to the need to ensure necessary appropriate action to safeguard children is always taken when child abuse or neglect are suspected.

Protecting children.

Safeguarding children from maltreatment and neglect is part of the responsibility of all health professionals, and dental practitioners may be in a unique position to recognise and respond to concerns of this kind. This article outlines some of the ways that abuse can present to the dental team and describes the action that should be taken if abuse is suspected in a young patient.

The spectrum of mutations causing HPRT deficiency: an update.

Mutations in the gene encoding hypoxanthine-guanine phosphoribosyltransferase (HPRT) cause Lesch-Nyhan disease, which is characterized by hyperuricemia, severe motor disability, and self-injurious behavior. Mutations in the same gene also cause less severe clinical phenotypes with only some portions of the full syndrome. A large database of 271 mutations associated with both full and partial clinical phenotypes was recently compiled. Since the original database was assembled, 31 additional mutations have been identified, bringing the new total to 302. The results demonstrate a very heterogeneous collection of mutations for both LND and its partial syndromes. The differences between LND and the partial phenotypes cannot be explained by differences in the locations of mutations, but the partial phenotypes are more likely to have mutations predicted to allow some residual enzyme function. The reasons for some apparent exceptions to this proposal are addressed.

Nucleotide degradation products in cerebrospinal fluid (CSF) in inherited and acquired pathologies.

CSF purines were grossly elevated compared with controls only in adenylosuccinate lyase (ADSL) deficiency and TB meningitis. The former representing low permeability, the latter severe damage to the normal blood/brain barrier. By contrast, the similarity to controls, with no difference between Lesch-Nyhan disease (LND) or LND variants, would exclude hypoxia as a factor in the severe neurological deficits in LND. Similar findings in purine nucleoside phosphorylase (PNP) deficiency (although nucleosides replace the normal bases) likewise exclude hypoxia in the aetiology of the albeit milder neurological deficits.

The plasma membrane of microaerophilic protists: oxidative and nitrosative stress.

The trans-plasma-membrane electrochemical potential of microaerophilic protists was monitored by the use of voltage-sensitive charged lipophilic fluorophores; of the many available probes, the anionic oxonol dye bis(1,3-dibarbituric acid)-trimethine oxonol [DiBAC(4)(3)] is an example of one which has been successfully employed using fluorescence microscopy, confocal laser-scanning microscopy and flow cytometry. Several microaerophilic protists have been investigated with this dye; these were Giardia intestinalis, Trichomonas vaginalis, Tritrichomonas foetus, Hexamita inflata and Mastigamoeba punctachora. Under conditions where they exhibit normal vitality, these organisms exclude DiBAC(4)(3) by virtue of their maintenance of a plasma-membrane potential (negative inside). Uptake of the fluorophore is indicative of disturbance to this membrane (i.e. by inhibition of pump/leak balance, blockage of channels or generation of ionic leaks), and is indicative of metabolic perturbation or environmental stress. Here, it is shown that oxidative or nitrosative stress depolarizes the plasma membranes of the aforementioned O(2)-sensitive organisms and allows DiBAC(4)(3) influx. Oxonol uptake thereby provides a sensitive and early indication of plasma-membrane perturbation by agents that may lead to cytotoxicity and eventually to cell death by necrotic or apoptotic pathways.

Nitrosative stress induced cytotoxicity in Giardia intestinalis.

AIMS: To investigate the antigiardial properties of the nitrosating agents: sodium nitrite, sodium nitroprusside and Roussin's black salt. METHODS AND RESULTS: Use of confocal laser scanning microscopy and flow cytometry indicated permeabilization of the plasma membrane to the anionic fluorophore, DiBAC4(3) [bis(1,3-dibutylbarbituric acid) trimethine oxonol]. Loss of plasma membrane electrochemical potential was accompanied by loss of regulated cellular volume control. Changes in ultrastructure revealed by electron microscopy and capacity for oxygen consumption, were also consequences of nitrosative stress. Roussin's black salt (RBS), active at micromolar concentrations was the most potent of the three agents tested. CONCLUSIONS: These multitargeted cytotoxic agents affected plasma membrane functions, inhibited cellular functions in Giardia intestinalis and led to loss of viability. SIGNIFICANCE AND IMPACT OF THE STUDY: Nitrosative damage, as an antigiardial strategy, may have implications for development of chemotherapy along with suggesting natural host defence mechanisms.

Dental disease and caries related microflora in children with dystrophic epidermolysis bullosa.

PURPOSE: The purpose of this study was to investigate dental caries, bacterial dental plaque, gingivitis and caries related oral microflora in children with predominantly autosomal recessive Dystrophic Epidermolysis Bullosa (DEB). METHODS: Thirty children with DEB from The Great Ormond Street Hospital for Children and 31 control children matched for age, gender and ethnicity were included in the study. RESULTS: The main findings were: 1. A significantly greater mean dmft in the DEB children (p < 0.05). 2. A significantly greater mean plaque score for the DEB children for both the primary (p < 0.001) and permanent teeth (p < 0.02) compared with the control children. 3. A significantly greater mean gingivitis score for the DEB children for both the primary (p < 0.002) and permanent teeth (p < 0.0001) compared with the control children. 4. A significantly greater salivary total anaerobic count for the control children compared with the DEB children (p < 0.001). CONCLUSIONS: The results reflect the difficulties that children with DEB have with basic oral hygiene procedures combined with slow oral clearance.

Are the Twelve Steps more acceptable to drug users than to drinkers? A comparison of experiences of and attitudes to Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) among 200 substance misusers attending inpatient detoxification.

The present study is a cross-sectional interview-based investigation comparing experiences of and attitudes towards Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) in a sample of 200 patients attending inpatient substance misuse detoxification services. Two hundred consecutive admissions were recruited; 100 each from one drug and one alcohol in-patient treatment service in which attendance at AA/NA was a voluntary adjunct to a generic treatment programme. Although there were no differences in the history of AA/NA attendance, the drug users (who were on average younger) reported significantly more positive attitudes towards AA/NA, more willingness to attend during their in-patient treatment and greater intention to attend following completion of their detoxification. In particular, despite no differences in spiritual/religious orientation, the drug users reported more positive views of the Twelve Steps. As AA/NA remain popular and accessible forms of substance misuse support, it is critical that we develop a clearer understanding of their impact and of the scope for their integration with generic forms of substance misuse treatment.

Ocular motor dysfunction in Lesch-Nyhan disease.

Eye movements were assessed in 22 patients with varying degrees of hypoxanthine-guanine phosphoribosyltransferase deficiency. Ocular motility was clinically normal in seven patients with moderate enzyme deficiency but grossly abnormal in 15 patients with severe enzyme deficiency. In patients with severe deficiency, fixation was interrupted by frequent unwanted saccades toward minor visual distractions. Voluntary saccades were associated with an initial head movement and/or eyeblink in all of these patients. When head motion was prevented, voluntary saccades were often delayed and sometimes absent. In contrast, saccade speed, reflexive saccades, and other reflexive eye movements appeared clinically normal. Four patients with severe enzyme deficiency also experienced mild blepharospasm, and two had ocular tics. These disturbances of ocular motility are consistent with dysfunction of the basal ganglia or its connections with ocular motor centers in the prefrontal cortex or midbrain.

Self-injurious behavior: gene-brain-behavior relationships.

This paper summarizes a conference held at the National Institute of Child Health and Human Development on December 6-7, 1999, on self-injurious behavior [SIB] in developmental disabilities. Twenty-six of the top researchers in the U.S. from this field representing 13 different disciplines discussed environmental mechanisms, epidemiology, behavioral and pharmacological intervention strategies, neurochemical substrates, genetic syndromes in which SIB is a prominent behavioral phenotype, neurobiological and neurodevelopmental factors affecting SIB in humans as well as a variety of animal models of SIB. Findings over the last decade, especially new discoveries since 1995, were emphasized. SIB is a rapidly growing area of scientific interest to both basic and applied researchers. In many respects it is a model for the study of gene-brain-behavior relationships in developmental disabilities.

Antigiardial drugs.

Giardia intestinalis is a world-wide cause of intestinal infection. Treatment of this debilitating disease is usually accomplished using one of several drugs. Metronidazole is the treatment of choice, but benzimidazoles are now being used more frequently. Other treatments include quinacrine, paromomycin and furazolidone. Even though these drugs are all used to treat the same disease, their modes of action differ in all cases. However, resistance is increasing and new alternatives are being sought. New wave antigiardials all appear to have their roots in natural herbal remedies. This mini-review looks at the current treatments available, their efficacy, side effects and different modes of action and addresses a possible way forward using natural products.

Antimicrobial properties of Allium sativum (garlic).

Although garlic has been used for its medicinal properties for thousands of years, investigations into its mode of action are relatively recent. Garlic has a wide spectrum of actions; not only is it antibacterial, antiviral, antifungal and antiprotozoal, but it also has beneficial effects on the cardiovascular and immune systems. Resurgence in the use of natural herbal alternatives has brought the use of medicinal plants to the forefront of pharmacological investigations, and many new drugs are being discovered. This review aims to address the historical use of garlic and its sulfur chemistry, and to provide a basis for further research into its antimicrobial properties.