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1.
PLoS One ; 14(8): e0221560, 2019.
Article in English | MEDLINE | ID: mdl-31442273

ABSTRACT

Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-stranded RNA virus that grows in macrophages and causes acute pneumonia in pigs. PRRSV causes devastating losses to the porcine industry. However, due to its high antigenic variability and poorly understood immunopathogenesis, there is currently no effective vaccine or treatment to control PRRSV infection. The common occurrence of PRRSV infection with bacterial infections as well as its inflammatory-driven pathobiology raises the question of the value of antibiotics with immunomodulating properties for the treatment of the disease it causes. The macrolide antibiotic Tulathromycin (TUL) has been found to exhibit potent anti-inflammatory and immunomodulating properties in cattle and pigs. The aim of this study was to characterize the anti-viral and immunomodulating properties of TUL in PRRSV-infected porcine macrophages. Our findings indicate that blood monocyte-derived macrophages are readily infected by PRRSV and can be used as an effective cellular model to study PRRSV pathogenesis. TUL did not change intracellular or extracellular viral titers, not did it alter viral receptors (CD163 and CD169) expression on porcine macrophages. In contrast, TUL exhibited potent immunomodulating properties, which therefore occurred in the absence of any direct antiviral effects against PRRSV. TUL had an additive effect with PRRSV on the induction of macrophage apoptosis, and inhibited virus-induced necrosis. TUL significantly attenuated PRRSV-induced macrophage pro-inflammatory signaling (CXCL-8 and mitochondrial ROS production) and prevented PRRSV inhibition of non-opsonized and opsonized phagocytic function. Together, these data demonstrate that TUL inhibits PRRSV-induced inflammatory responses in porcine macrophages and protects against the phagocytic impairment caused by the virus. Research in live pigs is warranted to assess the potential clinical benefits of this antibiotic in the context of virally induced inflammation and tissue injury.


Subject(s)
Disaccharides/pharmacology , Heterocyclic Compounds/pharmacology , Immunologic Factors/pharmacology , Macrophages/virology , Porcine Reproductive and Respiratory Syndrome/pathology , Porcine respiratory and reproductive syndrome virus/physiology , Animals , Antigens, CD , Antigens, Differentiation, Myelomonocytic , Apoptosis/drug effects , Cell Differentiation/drug effects , Cell Line , Cell Shape/drug effects , Disaccharides/therapeutic use , Female , Heterocyclic Compounds/therapeutic use , Immunologic Factors/therapeutic use , Interleukin-10/metabolism , Interleukin-8/metabolism , Intracellular Space/metabolism , Macrophages/drug effects , Male , Mice , Mitochondria/drug effects , Mitochondria/metabolism , Necrosis , Opsonin Proteins/metabolism , Phagocytosis/drug effects , Porcine Reproductive and Respiratory Syndrome/drug therapy , Porcine respiratory and reproductive syndrome virus/drug effects , Reactive Oxygen Species/metabolism , Receptors, Cell Surface , Receptors, Virus/metabolism , Sialic Acid Binding Ig-like Lectin 1/metabolism , Swine , Virus Replication/drug effects
2.
Neuropathol Appl Neurobiol ; 45(3): 195-215, 2019 04.
Article in English | MEDLINE | ID: mdl-30298527

ABSTRACT

Inflammation and neurodegeneration are key features of many chronic neurological diseases, yet the causative mechanisms underlying these processes are poorly understood. There has been mounting interest in the role of the human microbiome in modulating the inflammatory milieu of the central nervous system (CNS) in health and disease. To date, most research has focussed on a gut-brain axis, with other mucosal surfaces being relatively neglected. We herein take the novel approach of comprehensively reviewing the roles of the microbiome across several key mucosal interfaces - the nose, mouth, lung and gut - in health and in Parkinson's disease (PD), Alzheimer's disease (AD) and multiple sclerosis (MS). This review systematically appraises the anatomical and microbiological landscape of each mucosal surface in health and disease before considering relevant mechanisms that may influence the initiation and progression of PD, AD and MS. The cumulative effects of dysbiosis from the nose to the gut may contribute significantly to neurological disease through a wide variety of mechanisms, including direct translocation of bacteria and their products, and modulation of systemic or CNS-specific immunity. This remains an understudied and exciting area for future research and may lead to the development of therapeutic targets for chronic neurological disease.


Subject(s)
Alzheimer Disease/microbiology , Dysbiosis/microbiology , Inflammation/microbiology , Intestines/microbiology , Lung/microbiology , Microbiota , Mouth/microbiology , Multiple Sclerosis/microbiology , Nasal Cavity/microbiology , Olfaction Disorders/microbiology , Parkinson Disease/microbiology , Alzheimer Disease/complications , Humans , Multiple Sclerosis/complications , Olfaction Disorders/etiology , Parkinson Disease/complications
4.
Dis Esophagus ; 29(5): 497-502, 2016 Jul.
Article in English | MEDLINE | ID: mdl-25893778

ABSTRACT

Nutcracker esophagus (NE), Jackhammer esophagus (JHE), distal esophageal spasm (DES), and hypertensive lower esophageal sphincter (HTLES) are defined by esophageal manometric findings. Some patients with these esophageal motility disorders also have abnormal gastroesophageal reflux. It is unclear to what extent these patients' symptoms are caused by the motility disorder, the acid reflux, or both. The aim of this study was to determine the effectiveness of laparoscopic Nissen fundoplication (LNF) on esophageal motility disorders, gastroesophageal reflux, and patient symptoms. Between 2007 and 2013, we performed high-resolution esophageal manometry on 3400 patients, and 221 patients were found to have a spastic esophageal motility disorder. The medical records of these patients were reviewed to determine the manometric abnormality, presence of gastroesophageal symptoms, and amount of esophageal acid exposure. In those patients that underwent LNF, we compared pre- and postoperative esophageal motility, gastroesophageal symptom severity, and esophageal acid exposure. Of the 221 patients with spastic motility disorders, 77 had NE, 2 had JHE, 30 had DES, and 112 had HTLES. The most frequently reported primary and secondary symptoms among all patients were: heartburn and/or regurgitation, 69.2%; respiratory, 39.8%; dysphagia, 35.7%; and chest pain, 22.6%. Of the 221 patients, 192 underwent 24-hour pH monitoring, and 103 demonstrated abnormal distal esophageal acid exposure. Abnormal 24-hour pH monitoring was detected in 62% of patients with heartburn and regurgitation, 49% of patients with respiratory symptoms, 36.8 % of patients with dysphagia, and 32.6% of patients with chest pain. Sixty-six of the 103 patients with abnormal 24-hour pH monitoring underwent LNF. Thirty-eight (13NE, 2JHE, 6 DES, and 17 HTLES) of these 66 patients had a minimum of 6-month postoperative follow-up that included clinical evaluation, esophageal manometry, and 24-hour pH monitoring. Postoperatively, all 38 patients had normal distal esophageal acid exposure. Of these 38 patients, symptoms resolved in 28 and improved in 10. Of six patients (one with NE, two JHE, and three with HTLES) that underwent postoperative esophageal manometry, five exhibited normal motility. Typical reflux symptoms are common among patients with esophageal hypermotility disorders. Abnormal 24-hour pH monitoring is present in the majority of patients with who report typical reflux symptoms and almost half of patients who report respiratory symptoms. Conversely, the majority of patients who report dysphagia or chest pain have normal distal esophageal acid exposure. Based on a small number of patients in this study, it also appears that motility disorders often improve after LNF. LNF is associated with resolution or improvement in reflux related symptoms and esophageal motility parameters in patients exhibiting abnormal esophageal acid exposure. This suggests that patient symptoms are due to abnormal acid exposure and not the motility disorder.


Subject(s)
Esophageal Motility Disorders/surgery , Fundoplication/methods , Gastroesophageal Reflux/complications , Laparoscopy/methods , Adult , Aged , Aged, 80 and over , Deglutition Disorders/etiology , Deglutition Disorders/physiopathology , Esophageal Motility Disorders/complications , Esophageal Motility Disorders/physiopathology , Esophageal pH Monitoring , Esophagus/physiopathology , Esophagus/surgery , Female , Gastroesophageal Reflux/physiopathology , Heartburn/etiology , Heartburn/physiopathology , Humans , Male , Manometry , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
5.
Br Dent J ; 218(7): 423-8; discussion 428, 2015 Apr 10.
Article in English | MEDLINE | ID: mdl-25858740

ABSTRACT

OBJECTIVE: To analyse the factors affecting the clinical performance and those influencing the survival of resin-retained bridgework provided at a UK dental teaching hospital between 1994 and 2001. DESIGN: A prospective analysis of restorations provided at a single centre using case notes with all patients invited for review to corroborate findings. SETTING: Department of Restorative Dentistry, University of Bristol Dental Hospital and School, Bristol, United Kingdom. SUBJECTS AND METHODS: Between January 1994 and December 2001, data regarding 1,000 consecutive resin-retained bridges provided at Bristol Dental Hospital and School were recorded. Data was available for 805 patients at the time of the study. Following invitation, 621 patients attended for a review appointment. Life table and Kaplan-Meir survival analysis were carried out for all restorations provided. RESULTS: The five-year and ten-year survival rates estimated by the life-table method are 80.8% (95% confidence interval 78.0-83.6%) and 80.4% (95% confidence interval 77.6-83.2%) respectively. The median survival cannot be estimated for this study as the survival probability remains above 80% even at the longest follow-up. Analysis of clinical variables influencing survival revealed that design of the restoration and experience of the operator providing the restoration were significant factors. Resin-retained bridges made with minimal tooth preparation are shown to be superior in terms of longevity than those for which other types of tooth preparation is made. Patient satisfaction with their treatment was high.


Subject(s)
Dental Restoration Failure/statistics & numerical data , Denture, Partial, Fixed, Resin-Bonded/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Hospitals, Teaching/statistics & numerical data , Humans , Male , Middle Aged , Patient Satisfaction/statistics & numerical data , Prospective Studies , United Kingdom , Young Adult
6.
Ultrasound Obstet Gynecol ; 41(5): 589-91, 2013 May.
Article in English | MEDLINE | ID: mdl-23288807

ABSTRACT

The ductus venosus (DV) connects the portal venous system to the inferior vena cava. Rarely, the umbilical venous drainage is anomalous, either connecting to the portal sinus within the liver or having an extrahepatic connection, bypassing the liver and draining to one of a variety of sites, including to the heart directly. Prenatally, there is a recognized association of anomalous umbilical venous drainage with aneuploidy and other structural malformations. The fetus may also develop right heart failure because of unregulated volume loading. We report the postnatal development of diaphragmatic hernia in three fetuses with absent DV and umbilical venous drainage to the right atrium directly in two cases and to the coronary sinus in the third. In all fetuses, the abnormality was well-tolerated in pregnancy, with only a modest degree of right heart dilatation. All three neonates underwent repair of the diaphragmatic hernia and made a good recovery.


Subject(s)
Fetus/abnormalities , Hernia, Diaphragmatic/etiology , Umbilical Veins/abnormalities , Humans , Infant
7.
J Intellect Disabil Res ; 55(3): 302-12, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21199043

ABSTRACT

BACKGROUND: There are few well validated brief measures that can be used to assess the general progress of young children with autism spectrum disorders (ASD) over time. In the present study, the Autism Treatment Evaluation Checklist (ATEC) was used as part of a comprehensive assessment battery to monitor the progress of 22 school-aged children with ASD who had previously taken part in intensive home- or school-based intervention programmes in their pre-school years. METHODS: Parents completed the ATEC when the children were on average 5.5 years and then again 5-6 years later (mean age 10.4 years). Standardised measures were also used to assess cognitive, language and adaptive behaviour skills and severity of autism symptoms over the same period. RESULTS: The ATEC had high internal consistency at both time points. ATEC total and sub-scale scores remained relatively stable over time and were highly and significantly correlated with cognitive, language and adaptive behaviour skills and severity of autism symptoms at both assessment points. Initial ATEC total scores predicted 64% of the variance in scores at the subsequent follow-up. However, there was also considerable variation in the patterns of scores shown by individual children over time. CONCLUSIONS: This study provides some preliminary evidence of the ATEC's potential value for monitoring progress of children with ASD over time. Its advantages and limitations are discussed in the context of the need systematically to monitor the progress of children with ASD over time or in response to intervention.


Subject(s)
Child Development Disorders, Pervasive/therapy , Child Development , Disability Evaluation , Early Intervention, Educational , Outcome Assessment, Health Care/methods , Behavior Therapy , Child , Child Development Disorders, Pervasive/diagnosis , Child, Preschool , Cohort Studies , Humans , Longitudinal Studies , Male , Program Evaluation , Reproducibility of Results
8.
Hum Reprod ; 23(2): 421-6, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18084048

ABSTRACT

BACKGROUND: The role of LH in sensitizing antral follicles to FSH is unclear. LH is required for normal hormone production and normal oocyte and embryo development, but follicular responses to LH may depend upon the stage of development. Potential roles at the early follicular phase were explored in a clinical setting by employing a sequential approach to stimulation by recombinant human (r-h) LH followed by r-hFSH in women who were profoundly down-regulated by depo GnRH agonist. METHODS: We employed a multi-centre, prospective, randomized approach. Women (n = 146) were treated in a long course high-dose GnRH agonist (Decapeptyl, 4.2 mg s.c.) protocol and were randomized to receive r-hLH (Luveris, 300 IU/day) for a fixed 7 days, or no r-hLH treatment. This was followed by a standard r-hFSH stimulation regime (Gonal-F, 150 IU/day). Ultrasound and hormone assessments of responses were measured at the start of r-hLH treatment, on FSH stimulation Days 0 and 8 and at the time of HCG administration. RESULTS: The LH treatment was associated with increased small antral follicles prior to FSH stimulation (P = 0.007), and an increased yield of normally fertilized (2 PN) embryos (P = 0.03). There was no influence of the r-hLH pretreatment upon hormone profiles or ultrasound assessments during the FSH phase. Anti-mullerian hormone increased in both groups during the week prior to FSH stimulation (P = 0.002). CONCLUSIONS: This sequential approach to the use of r-hLH in standard IVF showed a possible modest clinical benefit. The results support other recent work exploring up-regulated androgen drive upon follicular metabolism indicating that clinical benefit may be obtainable after further practical explorations of the concept.


Subject(s)
Fertilization in Vitro , Follicle Stimulating Hormone, Human/pharmacology , Luteinizing Hormone/therapeutic use , Ovarian Follicle/drug effects , Ovarian Follicle/physiology , Adult , Anti-Mullerian Hormone/metabolism , Drug Administration Schedule , Embryo, Mammalian , Female , Fertilization , Humans , Luteinizing Hormone/administration & dosage , Ovarian Follicle/metabolism , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Treatment Outcome
9.
Heart ; 94(5): 581-4, 2008 May.
Article in English | MEDLINE | ID: mdl-17690157

ABSTRACT

BACKGROUND: In recent large paediatric cardiomyopathy population studies from North America and Australia, vitamin D deficiency was not identified as a cause of infant heart failure. However, rickets is resurgent in developed countries. OBJECTIVE: To review the prevalence of this cardiomyopathy in paediatric cardiology units of southeast England and determine the prognosis. METHODS AND RESULTS: A retrospective review from 2000 to 2006 in southeast England. Sixteen infants (6 Indian subcontinent, 10 black ethnicity) were identified: median (range) age at presentation was 5.3 months (3 weeks-8 months). All had been breast fed. Ten presented at the end of the British winter (February-May). Median shortening fraction was 10% (range 5-18%) and median left ventricular end diastolic dimension z score was 4.1 (range 3.1-7.0). Six had a cardiac arrest; three infants died. Eight were ventilated, two required mechanical circulatory support and 12 required intravenous inotropic support. Two were referred for cardiac transplantation. Median (range) of biochemical values on admission was: total calcium 1.5 (1.07-1.74) mmol/l; alkaline phosphatase 646 (340-1057) IU/l; 25-hydroxyvitamin D 18.5 (0-46) nmol/l (normal range >35) and parathyroid hormone 34.3 (8.9-102) pmol/l (normal range <6.1). The clinical markers and echocardiographic indices of all survivors have improved. The mean time from diagnosis to achieve normal fractional shortening was 12.4 months. CONCLUSIONS: Vitamin D deficiency and consequent hypocalcaemia are seen in association with severe and life-threatening infant heart failure. That no infant or mother was receiving the recommended vitamin supplementation highlights the need for adequate provision of vitamin D to ethnic minority populations.


Subject(s)
Heart Failure/etiology , Hypocalcemia/complications , Receptors, Calcitriol/metabolism , Vitamin D Deficiency/complications , Calcium/blood , Ethnicity , Female , Humans , Hypocalcemia/prevention & control , Infant , Infant, Newborn , Male , Pregnancy , Treatment Outcome , United Kingdom/ethnology , Vitamin D/therapeutic use
10.
J Pediatr ; 148(2): 213-6, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16492431

ABSTRACT

OBJECTIVE: To determine outcome of delivery before 36 weeks gestation in babies diagnosed antenatally with serious congenital heart disease (CHD). STUDY DESIGN: A retrospective database review at 2 tertiary care fetal cardiology centers. Details of neonatal course and outcome were obtained for those antenatally diagnosed with serious CHD who were live born before 36 weeks gestation. RESULTS: Between January 1998 and December 2002, 9918 women were referred for fetal echocardiography. Serious CHD was diagnosed in 1191 fetuses (12%), of which 46 (4%) delivered prematurely. Median gestation was 33 (range 24-35) weeks, and median birth weight 1.56 (0.50-3.59) kg. Extracardiac/karyotypic anomalies occurred in 23 (50%). Twenty-six babies (57%) underwent neonatal surgery: 16 a cardiac procedure, 5 a general surgical procedure, and 5 both. Eight died during or after operation (31%). Two babies underwent interventional heart catheterization; both died. The overall mortality rate was 72%. Extracardiac/karyotypic anomalies increased the relative risk of death by a factor of 1.36. Mean hospital stay for those surviving to initial discharge was 46 (2-137) days. CONCLUSIONS: There is a very high morbidity and mortality rate in this group, particularly for those with extracardiac/karyotypic anomalies. This should be reflected in decisions over elective preterm delivery and when counseling parents.


Subject(s)
Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/mortality , Premature Birth , Prenatal Diagnosis , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/mortality , Adolescent , Adult , Birth Weight , Chromosome Aberrations , Echocardiography , Female , Gestational Age , Heart Defects, Congenital/therapy , Humans , Infant , Infant, Newborn , Length of Stay , Pregnancy , Retrospective Studies , Risk Factors , Survival Analysis , United Kingdom/epidemiology
11.
Hum Reprod ; 21(6): 1436-41, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16439501

ABSTRACT

BACKGROUND: During excess FSH treatment, different categories of follicles can be discerned: those responding and appearing to grow immediately (FolsS8) and those appearing subsequently during the follicular phase (Fols/d). These follicular categories were explored in cycles of assisted reproduction in the context of follicular biology, including primordial follicle pool (PFP) depletion, age, insulin resistance and potential markers. METHODS: Follicular cohorts were examined in 365 conventional ART cycles and related to patient insulin sensitivity, plasma FSH and anti-Mullerian hormone (AMH). RESULTS: Age had no influence upon the FolsS8 category but was associated with a significant (P < 0.005) decline in the Fols/d. In contrast, insulin-resistant polycystic ovary syndrome (IR-PCOS) showed a significant (P = 0.005) increase in FolsS8. Circulating AMH correlated strongly with oocyte yield and Fols/d. CONCLUSION: Age showed little impact on the initial follicular cohort, but a significant impact upon the secondary cohort, while insulin resistance appeared to promote the former category alone. The disturbance to follicular dynamics and AMH in IR-PCOS reflected a larger stockpile of FSH-sensitive follicles. Circulating AMH appears to represent all categories of antral follicles observed.


Subject(s)
Follicle Stimulating Hormone/therapeutic use , Glycoproteins/metabolism , Infertility, Female/drug therapy , Oocytes/metabolism , Ovarian Follicle/drug effects , Testicular Hormones/metabolism , Adult , Age Factors , Anti-Mullerian Hormone , Body Mass Index , Cohort Studies , Female , Humans , Insulin/metabolism , Insulin Resistance , Ovarian Follicle/metabolism , Ovulation Induction , Polycystic Ovary Syndrome/drug therapy
12.
Heart ; 92(3): 382-7, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16118238

ABSTRACT

OBJECTIVE: To determine the accuracy of prenatal and postnatal echocardiography in delineating the degree of cardiac fusion, intracardiac anatomy (ICA), and ventricular function of 23 sets of conjoined twins with thoracic level fusion presenting to a single centre over a 20 year period. METHODS: 13 thoracopagus, 5 thoraco-omphalopagus, and 5 parapagus pairs presenting to the authors' institution between 1985 and 2004 inclusive were assessed. Echocardiographic data were analysed together with operative intervention and outcome. Twins were classified according to the degree of cardiac fusion: separate hearts and pericardium (group A, n = 5), separate hearts and common pericardium (group B, n = 7), fused atria and separate ventricles (group C, n = 2), and fused atria and ventricles (group D, n = 9). RESULTS: The degree of cardiac fusion was correctly diagnosed in all but one set. ICA was correctly diagnosed in all cases, although the antenatal diagnosis was revised postnatally in three cases. Abnormal ICA was found in one twin only in two group A pairs, one group B pair, and both group C pairs. All group D twins had abnormal anatomy. Ventricular function was good in all twins scanned prenatally, and postnatally function correlated well with clinical condition. Thirteen sets of twins in groups A-C were surgically separated; 16 of 26 survived. None from groups C or D survived. CONCLUSIONS: Prenatal and postnatal echocardiography accurately delineates cardiac fusion, ICA, and ventricular function in the majority of twins with thoracic level fusion. It is integral in assessing feasibility of separation. The outcome in twins with fused hearts remains dismal.


Subject(s)
Echocardiography/standards , Heart Defects, Congenital/ultrastructure , Perinatal Care/standards , Twins, Conjoined , Ultrasonography, Prenatal/standards , Ventricular Dysfunction, Left/diagnostic imaging , Female , Humans , Infant, Newborn , Male , Sensitivity and Specificity , Twins, Conjoined/surgery
13.
Aust N Z J Public Health ; 29(5): 457-60, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16255448

ABSTRACT

OBJECTIVE: Supplementary questionnaires provide additional information from subgroups, but may have an attritional effect on response rates. We examined the effects of different instruction methods on response rates to a two-part questionnaire. METHODS: The ACT Kindergarten Health Survey comprises a health questionnaire for all school-entry children. A supplementary questionnaire targets children with respiratory symptoms. We cluster-randomised 109 schools in the ACT (4,494 children) to two instruction groups. Group 1 (instruction burden) had instructions to complete the supplementary questionnaire if certain questions in the primary questionnaire were answered. Group 2 (response burden) had instructions to complete both questionnaires irrespective of answers to the primary questionnaire. RESULTS: Instructing all respondents to complete both questionnaires regardless of eligibility resulted in a statistically significantly lower primary questionnaire response rate (82% vs. 87%), but a statistically significantly higher response rate to the supplementary questionnaire (99% vs. 91%). The net effect was a small overall gain (82% vs. 79%) for the response burden group. CONCLUSION: Increasing the response burden had a minor impact on response rate to the primary questionnaire, but increased the response rate for most items to the supplementary questionnaire. IMPLICATIONS: Large surveys may be broken into primary and supplementary questionnaires, if strategies to maximise response rates are used. Questionnaires may need to be modified to take into account the likely attrition on response to either questionnaire resulting from instruction and response burdens.


Subject(s)
Quality Control , Surveys and Questionnaires , Teaching , Child , Cluster Analysis , Humans , Respiratory System/physiopathology
14.
Cephalalgia ; 25(12): 1103-9, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16305598

ABSTRACT

Nine healthy volunteers aged 18-28 years were recruited into this open, single-centre, two-phase trial. In phase 1, two volunteers received a single dose of 11C-zolmitriptan 2.5 mg administered as a nasal spray and then underwent positron emission tomography (PET) scanning to determine the most appropriate times for scanning in phase 2. In phase 2, six volunteers received two doses and an additional volunteer one dose of 11C-zolmitriptan 2.5 mg intranasally. Volunteers underwent PET scanning over sectors covering one of the nasopharynx, lungs or abdomen, for up to 1.5 h postdose. The brain was also scanned and plasma zolmitriptan levels were measured. Almost 100% of the administered dose was detected in the nasopharynx immediately after dosing. This declined thereafter to about 50% at 20 min and to 35% at 80 min after dosing. Radioactivity appeared slowly in the upper abdomen, with 25% of given radioactivity detected at 20 min and persisting until 80 min after dosing. Minimal radioactivity was detected in the lungs. Radioactivity was detectable within brain tissue suggesting central penetration of zolmitriptan. Zolmitriptan in plasma had approached its maximum concentration by 15 min postdose. The data indicate initial absorption across the nasal mucosa contributing to an early systemic availability. 11C-Zolmitriptan administered intranasally was well tolerated.


Subject(s)
Nasal Mucosa/metabolism , Nasopharynx/metabolism , Oxazolidinones/administration & dosage , Oxazolidinones/pharmacokinetics , Positron-Emission Tomography/methods , Respiratory Mucosa/metabolism , Tryptamines/administration & dosage , Tryptamines/pharmacokinetics , Administration, Inhalation , Adolescent , Adult , Brain , Carbon Radioisotopes/pharmacokinetics , Female , Humans , Male , Metabolic Clearance Rate , Nasopharynx/diagnostic imaging , Nose/diagnostic imaging , Organ Specificity , Radiopharmaceuticals/pharmacokinetics , Respiratory Mucosa/diagnostic imaging , Serotonin Receptor Agonists/administration & dosage , Serotonin Receptor Agonists/pharmacokinetics , Tissue Distribution
15.
J Dent ; 33(1): 19-25, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15652164

ABSTRACT

OBJECTIVES: The recent tendency for toothpaste manufacturers to combine active ingredients for benefits to a number of oral problems requires that such combinations do not vitiate the action of any one agent. The aim of this study was to compare the desensitising effects of a modified formulation with the established product. MATERIALS AND METHODS: The study was a randomised, double blind, two treatment parallel design comparing an existing potassium citrate toothpaste product (Positive Control) with the same formulation to which triclosan and zinc citrate had been added (Test). A total of 56 subjects with dentine hypersensitivity (DH) completed the 8 week study period. At baseline, days 14 and 56 visual analogue scale scores were recorded by the subjects in response to air evaporative and cold water stimuli. RESULTS: Both groups showed improvements, mostly statistically significant, from baseline to day 14 and through to day 56. Most data favoured the Test paste but differences were, for the most part, not significant. CONCLUSIONS: It is concluded that the addition of known anti-plaque agents to an established potassium salt based desensitising toothpaste did not adversely affect the activity of the product in the treatment of DH.


Subject(s)
Dentin Sensitivity/drug therapy , Toothpastes/therapeutic use , Anti-Infective Agents, Local/therapeutic use , Citric Acid/therapeutic use , Double-Blind Method , Humans , Potassium Citrate/therapeutic use , Toothpastes/chemistry , Triclosan/therapeutic use , Zinc/therapeutic use
16.
Hum Reprod ; 20(3): 756-60, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15608033

ABSTRACT

BACKGROUND: Controlled ovulation induction and intrauterine insemination (OI-IUI) is associated with multiple pregnancies, which are a cause of much concern. No reliable datasets have shown clear criteria for predicting multiple pregnancy. The aim of this study was to eliminate a number of variables by examining only conception cycles to determine ultrasound criteria posing risks of multiple pregnancy. METHODS: 112 OI-IUI conception cycles (multiple pregnancy rate 19.6%) were analysed retrospectively to identify factors that may be used to evaluate multiple pregnancy risk. Analyses of ultrasound data on the day of hCG administration allowed study of the role of primary, secondary and tertiary follicle diameters (FD). RESULTS: There were no multiple pregnancies in cases where there was a single FD > or = 14 mm, and no higher-order pregnancies where the tertiary follicle measured <14 mm. Follicles with an FD of 15 mm showed an 8% attributable implantation rate. CONCLUSIONS: Revision of the criteria for administration of the ovulatory dose of hCG should include the concept that follicles of 15 mm diameter may yield a pregnancy. We suggest that rigorous application of such criteria (critical FD of 16 mm combined with secondary FD evidence) will not reduce the programme pregnancy rate, but will reduce the incidence of multiple conceptions.


Subject(s)
Fertilization , Insemination, Artificial , Ovarian Follicle/diagnostic imaging , Ovulation Induction , Pregnancy, Multiple , Adult , Embryo Implantation , Female , Humans , Pregnancy , Pregnancy, Multiple/statistics & numerical data , Retrospective Studies , Risk Assessment , Ultrasonography
17.
J Clin Periodontol ; 31(12): 1106-9, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15560813

ABSTRACT

OBJECTIVES: Plaque scoring usually employs subjective indices. The aim was to compare plaque inhibition of three toothpastes using two objective and one subjective measures of plaque. MATERIAL AND METHODS: Formulations were: (1) an experimental anti-plaque paste (test); (2) an experimental paste (minus active or negative control); and (3) a proprietary anti-plaque toothpaste product (positive control). The study was a blind, randomised crossover design using a 4-day, no tooth brushing, plaque regrowth model and involving 22 healthy subjects. After baseline plaque removal, subjects rinsed twice a day with slurries of the allocated paste. On day 5, plaque was scored by index, wet weight and optical density of extracted disclosing solution from the plaque (stain intensity). RESULTS: All data showed the same pattern. There were highly significant subject and treatment effects but not period effects. The positive control was highly significantly more effective in plaque control than the test and minus active experimental formulations, which in turn were not significantly different from each other. There were strong and significant correlations between pairs of scoring methods particularly wet weight and stain intensity. CONCLUSION: The use of objective methods of plaque alongside conventional subjective indices provided convincing evidence for increased discriminatory power in a study comparing plaque inhibition by toothpastes.


Subject(s)
Dental Plaque Index , Dental Plaque/prevention & control , Mouthwashes/therapeutic use , Outcome Assessment, Health Care/methods , Toothpastes/therapeutic use , Adult , Epidemiologic Methods , Female , Humans , Male , Mouthwashes/chemistry , Sodium Dodecyl Sulfate/therapeutic use , Tooth Discoloration/prevention & control , Toothpastes/chemistry
18.
J Clin Periodontol ; 31(10): 885-9, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15367193

ABSTRACT

OBJECTIVES: Potassium and fluoride salts have been used in the treatment of dentine hypersensitivity (DH). The primary aim of this study was to compare a fluoride-containing mouthrinse product with a placebo rinse for the treatment of DH. A secondary aim was to compare effects on plaque index (PI) and gingivitis index (GI). MATERIAL AND METHODS: The study was a double-blind, randomised, two-treatment parallel design involving 91 subjects with DH. At screening, an air evaporative stimulus (AES) was used for selection. Approximately 4 weeks later, at the baseline visit, DH was recorded, using a response-based visual analogue scale (VAS) from upper and lower incisors, canines, premolars and first molars in response to AES and from two to six teeth in response to a cold water stimulus (CWS). PI and GI were also recorded. Subjects were then allocated the test or placebo rinse. On days 28 and 56, VAS scores were again recorded for AES and CWS, with PI and GI recorded at day 56. RESULTS: Both groups improved symptoms to day 28 and again to day 56. The majority of the data favoured the test rinse as more effective but there was no clear evidence for a statistically significant difference between test and placebo. PI at lingual sites approached significance for the test rinse. CONCLUSIONS: The placebo response has again been shown to play a significant role in DH clinical trials and narrows the range over which to detect treatment differences. Study designs to minimise or prevent the placebo response in DH seem worthy of consideration.


Subject(s)
Dentin Sensitivity/drug therapy , Fluorides/therapeutic use , Mouthwashes/therapeutic use , Adolescent , Adult , Aged , Analysis of Variance , Dental Plaque Index , Double-Blind Method , Female , Humans , Male , Middle Aged , Periodontal Index , Placebo Effect , Statistics, Nonparametric , Time Factors
20.
J Paediatr Child Health ; 39(7): 534-9, 2003.
Article in English | MEDLINE | ID: mdl-12969209

ABSTRACT

OBJECTIVES: To measure the prevalence of respiratory symptoms and atopic disease in Aboriginal and Torres Strait Islander (indigenous) and non-indigenous children in the Australian Capital Territory (ACT). METHODS: A two-stage questionnaire survey of children in the ACT with stage two completed for children identified by parents as having respiratory symptoms or asthma in the first stage cross-sectional survey. Participants in the study were: (i) all new entrant primary schoolchildren aged 4-6 years in 1999, 2000 and 2001, 217 being indigenous children and 10 604 being non-indigenous children (80% of eligible); and (ii) Year 1-6 primary schoolchildren in 2000, with 216 being indigenous children and 14 202 being non-indigenous children (52% of eligible). Respiratory symptoms (including recent wheeze and parent-reported asthma) and other factors were measured by parental questionnaire. RESULTS: Indigenous kindergarten children had more recent wheeze (21%, odds ratio (OR) 1.4 95% confidence interval (CI) 1.0-2.0)) and parent-reported asthma (24%, OR 1.8 95% CI 1.3-2.5) than non-indigenous children (both 15%). However, indigenous children had less eczema (25%, OR 0.7 95% CI 0.5-0.9) and hayfever (14%, OR 0.7 95% CI 0.5-1.0) than non-indigenous children (32% and 19%, respectively). Among children with respiratory symptoms, the symptom severity did not differ between groups, but indigenous children were exposed to more environmental tobacco smoke (ETS) (63%, OR 3.5 95% CI 2.1-5.9) than non-indigenous children (32%). CONCLUSIONS: Indigenous children in the ACT have more respiratory morbidity but less of the atopic diseases of hayfever and eczema than non-indigenous children. Whether the respiratory morbidity represents 'asthma' or results from increased ETS exposure is unclear and needs to be further explored.


Subject(s)
Native Hawaiian or Other Pacific Islander , Respiratory Tract Diseases/epidemiology , Australian Capital Territory/epidemiology , Child , Child, Preschool , Female , Humans , Male , Surveys and Questionnaires
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