ABSTRACT
BACKGROUND: Children with obesity are more likely to suffer gastroesophageal reflux disease, requiring acid-suppression therapy with proton pump inhibitors (PPIs) and no guidelines regarding dosing. OBJECTIVE: To prospectively evaluate lean-body-weight-based (LBW) dosing of the PPI pantoprazole for children with and without obesity. METHODS: Methods: Sixty-two children (6-17 years) received a one-time oral dose of liquid pantoprazole (1.2 mg kg-1 LBW). Plasma pantoprazole concentrations were measured at 10 time points over 8 h and pharmacokinetic (PK) profiles generated using non-compartmental techniques, in order to compare PK parameters of interest between children with and without obesity, while accounting for CYP2C19 genotype. RESULTS: Adjusted for milligram-per-kilogram total body weight (TBW) pantoprazole received, apparent drug clearance (CL/F) was reduced 50% in children with vs. without obesity (p=0.03). LBW-based dosing compensated for this reduction in CL/F (p = 0.15). CONCLUSION: To achieve comparable systemic PPI exposures for children with and without obesity, we recommend using LBW, rather than TBW-based dosing for pantoprazole.
Subject(s)
Body Weight/drug effects , Gastroesophageal Reflux/drug therapy , Pantoprazole/administration & dosage , Pediatric Obesity/complications , Proton Pump Inhibitors/administration & dosage , Adolescent , Child , Cytochrome P-450 CYP2C19/genetics , Drug Dosage Calculations , Female , Follow-Up Studies , Gastroesophageal Reflux/etiology , Genotype , Humans , Male , Pantoprazole/pharmacokinetics , Pediatric Obesity/drug therapy , Prospective Studies , Proton Pump Inhibitors/pharmacokineticsABSTRACT
BACKGROUND: Peppermint oil has been used for centuries as a treatment for gastrointestinal ailments. It has been shown to have several effects on gastrointestinal physiology relevant to clinical care and management. AIM: To review the literature on peppermint oil regarding its metabolism, effects on gastrointestinal physiology, clinical use and efficacy, and safety. METHODS: We performed a PubMed literature search using the following terms individually or in combination: peppermint, peppermint oil, pharmacokinetics, menthol, oesophagus, stomach, small intestine, gallbladder, colon, transit, dyspepsia, nausea, abdominal pain, and irritable bowel syndrome. Full manuscripts evaluating peppermint oil that were published through 15 July 2017 were reviewed. When evaluating therapeutic indications, only randomised clinical trials were included. References from selected manuscripts were used if relevant. RESULTS: It appears that peppermint oil may have several mechanisms of action including: smooth muscle relaxation (via calcium channel blockade or direct enteric nervous system effects); visceral sensitivity modulation (via transient receptor potential cation channels); anti-microbial effects; anti-inflammatory activity; modulation of psychosocial distress. Peppermint oil has been found to affect oesophageal, gastric, small bowel, gall-bladder, and colonic physiology. It has been used to facilitate completion of colonoscopy and endoscopic retrograde cholangiopancreatography. Placebo controlled studies support its use in irritable bowel syndrome, functional dyspepsia, childhood functional abdominal pain, and post-operative nausea. Few adverse effects have been reported in peppermint oil trials. CONCLUSION: Peppermint oil is a natural product which affects physiology throughout the gastrointestinal tract, has been used successfully for several clinical disorders, and appears to have a good safety profile.
Subject(s)
Gastrointestinal Diseases/drug therapy , Gastrointestinal Tract/drug effects , Irritable Bowel Syndrome/drug therapy , Plant Oils/pharmacology , Plant Oils/therapeutic use , Abdominal Pain/drug therapy , Abdominal Pain/etiology , Abdominal Pain/physiopathology , Child , Dyspepsia/complications , Dyspepsia/drug therapy , Dyspepsia/physiopathology , Gastrointestinal Diseases/complications , Gastrointestinal Diseases/physiopathology , Gastrointestinal Tract/physiology , Humans , Irritable Bowel Syndrome/complications , Mentha piperita , Plant Oils/adverse effects , Plant Oils/pharmacokinetics , Treatment OutcomeABSTRACT
Melnick-Needles syndrome (MNS) is a rare congenital X-linked dominant skeletal dysplasia, characterized by exophthalmos, a prominent forehead, and mandibular hypoplasia and retrognathism. Dental features may include anodontia, hypodontia, or oligodontia. Increased collagen content, unpredictable collagen synthesis, and abnormal bony architecture have raised concerns regarding bone splitting intraoperatively and bone healing postoperatively. This report describes the cases of two sisters with MNS, who successfully underwent orthognathic surgery consisting of bilateral mandibular ramus osteotomies combined with advancement genioplasty and iliac crest bone grafting, to correct the classical MNS facial deformity of mandibular retrognathia.
Subject(s)
Orthognathic Surgical Procedures , Osteochondrodysplasias/surgery , Adult , Female , Humans , Osteochondrodysplasias/diagnostic imaging , SiblingsABSTRACT
BACKGROUND: Odontogenic myxoma is a benign odontogenic tumour of the jaw [1]. This tumour often presents as an asymptomatic expansile lesion without sensory nerve changes [2]. It is thought to arise from mesenchymal origin with cells of microscopic similarity to dental pulp and follicle [3]. Radiographically it presents most often as a multiloculated radiolucency [2]. It is a locally aggressive lesion which may require extensive treatment to prevent recurrence. METHOD: The authors present the case of a 13-year-old boy with an extensive lesion in the maxilla. CONCLUSION: We discuss various treatment approaches for management of this tumour.
Subject(s)
Maxilla/pathology , Myxoma/pathology , Odontogenic Tumors/pathology , Adolescent , Humans , Male , Maxilla/surgery , Myxoma/surgery , Neoplasm Recurrence, Local , Odontogenic Tumors/surgeryABSTRACT
Melanotic neuroectodermal tumour of infancy (MNTI) is a rare pigmented neoplasm of neural crest origin. It usually presents in the first year of life in the maxilla as a fast growing lesion. We describe the case of a 3-month-old boy who presented with an enlarging swelling of left maxillary alveolus. He was treated with combined surgical and chemotherapy modalities. MNTI is complicated by high recurrence rate, local invasion and malignancy has been reported. This report describes the diagnosis, treatment and follow-up of recurrent MNTI.
Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Maxillary Neoplasms/surgery , Neuroectodermal Tumor, Melanotic/surgery , Vincristine/therapeutic use , Combined Modality Therapy , Humans , Infant , Male , Maxillary Neoplasms/drug therapy , Neuroectodermal Tumor, Melanotic/drug therapy , Treatment OutcomeABSTRACT
Appropriate pediatric dose selection remains one of the most vexing clinical problems faced by healthcare professionals who are charged to provide medical care to infants and children. While body size does reflect the ontogeny of processes that govern drug disposition, there are extremes of disease that perturb the expected relationships.
Subject(s)
Body Size , Drug Dosage Calculations , Pharmaceutical Preparations/administration & dosage , Age Factors , Child , Child, Preschool , Comorbidity , Dose-Response Relationship, Drug , Drug-Related Side Effects and Adverse Reactions/etiology , Drug-Related Side Effects and Adverse Reactions/prevention & control , Humans , Infant , Infant, Newborn , Patient Safety , Pharmaceutical Preparations/metabolism , Pharmacogenetics , Pharmacokinetics , Risk Assessment , Risk FactorsABSTRACT
BACKGROUND: Reconstruction of a urethral stricture poses a difficult surgical problem. Anastomotic repair remains the gold standard. Strictures longer than 2 cm may require substitution urethroplasty. This is a retrospective review of all patients who underwent urethral reconstruction with an autologous free buccal mucosa graft at a Regional hospital between 1998 and 2009. METHODS: Variables recorded included; demographics: patient gender/age; follow-up period. Urology: pre-operative diagnosis/aetiology; presenting complaint; previous urological surgery, pre-operative retrograde urethrogram, stricture length, graft size, operative time/blood loss, morbidity, complications. Maxillofacial: pre-/post-operative inter-incisal opening, patency of Stenson's parotid duct, ipsilateral parotid swelling, sensory nerve deficit. RESULTS: A total of eight male patients were included. Mean age was 33 years. Two patients had one-stage dorsal onlay urethroplasty, and the remaining six had a two-stage BMG urethroplasty. All patients underwent a urethrogram 20 days post-operatively, which demonstrated no leak, and a good caliber grafted urethra in all cases. A flexible cystoscopy scope was accommodated in all patients 8 weeks post-operatively. Mean follow-up was 42 months. At long-term follow-up, there was no evidence of stricture formation, and all patients were voiding well. There were no long-term intra-oral complications. CONCLUSION: This study suggests that anterior urethral strictures up to 6 cm in length may be predictably and safely managed with buccal mucosal urethroplasty. The buccal mucosa is easy to harvest, and can be used successfully in one- and two-stage grafting procedures. The rate of complications, from both a urological and maxillofacial perspective, in the group of patients studied was low.
Subject(s)
Mouth Mucosa/transplantation , Plastic Surgery Procedures/methods , Urethral Stricture/surgery , Urologic Surgical Procedures, Male/methods , Adult , Blood Loss, Surgical , Humans , Male , Middle Aged , Postoperative Period , Retrospective Studies , Treatment Outcome , Urethra/surgery , Wound Healing , Young AdultABSTRACT
OBJECTIVES: In premature infants with suspected intra-abdominal infection, biomarkers for treatment response to antimicrobial therapy are lacking. Intestinal fatty acid-binding protein (I-FABP) is specific to the enterocyte and is released in response to intestinal mucosal injury. I-FABP has not been evaluated as a surrogate marker of disease response to antimicrobial therapy. We examined the relationship between metronidazole exposure and urinary I-FABP concentrations in premature infants with suspected intra-abdominal infection. STUDY DESIGN: We conducted an intravenous metronidazole pharmacokinetic study, collecting ≤3 urine samples per infant for I-FABP concentration measurements. We analyzed the relationship between I-FABP concentrations and measures of metronidazole exposure and pharmacokinetics, maturational factors, and other covariates. RESULTS: Twenty-six samples from 19 premature infants were obtained during metronidazole treatment. When analyzed without regard to presence of necrotic gastrointestinal disease, there were no significant associations between predictor variables and I-FABP concentrations. However, when the sample was limited to premature infants with necrotic gastrointestinal disease, an association was found between average predicted metronidazole concentration and I-FABP concentration (p = 0.006). CONCLUSION: While a predictive association between urinary I-FABP and metronidazole systemic exposure was not observed, the data suggest the potential of this endogenous biomarker to serve as a pharmacodynamic surrogate for antimicrobial treatment of serious abdominal infections in neonates and infants.
Subject(s)
Anti-Infective Agents/pharmacokinetics , Fatty Acid-Binding Proteins/urine , Infant, Premature, Diseases/drug therapy , Intraabdominal Infections/drug therapy , Metronidazole/pharmacokinetics , Anti-Infective Agents/therapeutic use , Biomarkers/urine , Enterocolitis, Necrotizing/drug therapy , Enterocolitis, Necrotizing/urine , Female , Humans , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/urine , Infusions, Intravenous , Intraabdominal Infections/urine , Linear Models , Male , Metronidazole/therapeutic use , Prospective Studies , Treatment OutcomeABSTRACT
We present a previously undescribed skeletal dysplasia with dental anomalies and ectopic neural tissue in the internal auditory meati.
Subject(s)
Abnormalities, Multiple/pathology , Bone Diseases, Developmental/pathology , Craniofacial Abnormalities/pathology , Facial Bones/abnormalities , Tooth Abnormalities/pathology , Abnormalities, Multiple/genetics , Child , Child, Preschool , Choristoma/pathology , Female , Humans , Nerve Tissue , SyndromeABSTRACT
We present a case of life-threatening streptococcal sepsis in a young man with a history of Behçet's disease within two weeks of commencing high dose corticosteroid therapy for an exacerbation of Behçet's disease.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Behcet Syndrome/drug therapy , Extracorporeal Membrane Oxygenation , Prednisolone/administration & dosage , Sepsis/therapy , Streptococcal Infections/therapy , Adult , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/adverse effects , Azathioprine/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Male , Prednisolone/adverse effects , Sepsis/etiology , Streptococcal Infections/complicationsABSTRACT
Therapy with fresh frozen plasma (FFP) confers serious risks, such as contraction of blood-borne viruses, allergic reaction, volume overload and development of alloantibodies. The aim of this study was to apply principles of pharmacokinetic (PK) modelling to individual factor content of FFP to optimize individualized dosing, while minimizing potential risks of therapy. We used PK modelling to successfully target individual factor replacement in an 8-month-old patient receiving FFP for treatment of a severe congenital factor V (FV) deficiency. The model fit for the FV activity vs. time data was excellent (r = 0.98) and the model accurately predicted FV activity during the intraoperative and postoperative period. Accurate PK modelling of individual factor activity in FFP has the potential to provide better targeted therapy, enabling clinicians to more precisely dose patients requiring coagulation products, while avoiding wasteful and expensive product overtreatment, minimizing potentially life-threatening complications due to undertreatment and limiting harmful product-associated risks.
Subject(s)
Blood Component Transfusion , Coagulants/pharmacokinetics , Factor V Deficiency/therapy , Factor VIII/pharmacokinetics , Plasma , Blood Component Transfusion/adverse effects , Blood Component Transfusion/methods , Factor V Deficiency/metabolism , Humans , Infant , Male , Models, BiologicalABSTRACT
BACKGROUND: Giant cell granulomas (GCGs) are benign tumours of the jaws of unknown aetiology. Aggressive lesions are difficult to manage and demonstrate a tendency to recur after surgical curettage. In the early 1980s, interferon alpha-2a was found to inhibit angiogenesis through a series of laboratory experiments and was subsequently used to treat a child with pulmonary haemangiomatosis. It has been hypothesised that GCGs are proliferative vascular lesions and would, therefor, be expected to respond to antiangiogenic therapy. The purpose of this study is to report a treatment protocol consisting of enucleation, followed by subcutaneous interferon alpha. METHODS: Patients with a biopsy-confirmed giant cell lesion satisfying criteria for "aggressive" giant cell tumours were included. All lesions were enucleated, and the patients commenced interferon alpha-2a (3,000,000 units/m(2)) 48-72 h post-operatively. RESULTS: Two patients satisfied the criteria for aggressive giant cell lesions. All tumours were enucleated. There were no post-operative complications, and all patients tolerated the interferon therapy well. To date, there has been no evidence of tumour recurrence. The follow-up periods were 144 and 81 months, respectively. CONCLUSION: Antiangiogenic therapy, in combination with curettage, has proven to be a useful strategy for the management of these tumours. The use of interferon alpha-2a, following enucleation of these lesions, resulted in complete remission of all lesions, and decreased operative morbidity compared with conventional treatment.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Granuloma, Giant Cell/drug therapy , Interferon-alpha/therapeutic use , Jaw Neoplasms/drug therapy , Adult , Child , Combined Modality Therapy , Female , Granuloma, Giant Cell/surgery , Humans , Interferon alpha-2 , Jaw Neoplasms/surgery , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/surgery , Recombinant Proteins/therapeutic useABSTRACT
BACKGROUND: Airway management in patients undergoing maxillofacial surgery requires special consideration. A number of options including oro- or naso-tracheal intubation and tracheostomy are available. Submental intubation is now a recognised method of airway control during maxillofacial surgery. It provides a secure airway and does not interfere with maxillomandibular fixation or access to naso-orbito-ethmoid fractures. It avoids potential complications associated with nasotracheal intubation and tracheostomy in patients with multiple facial fractures, and obviates the need to alternate between oral and nasal intubation intra-operatively. METHODS: This is a ten year retrospective review of patients who underwent submental intubation in a Regional Oral and Maxillofacial Surgery Department. The following variables were recorded: patient gender and age, preoperative diagnosis, duration of intubation, and complications associated with the intubation technique. RESULTS: Submental intubation was performed 45 times on 45 patients. There were no complications relating to the submental intubation procedure. CONCLUSION: Submental intubation should be considered as an option for airway management in selected cases of craniomaxillofacial surgery. It is a quick and safe technique with minimal morbidity and a low complication rate. It allows access to the maxillofacial skeleton intra-operatively and does not preclude the use of intermaxillary fixation.
Subject(s)
Intubation, Intratracheal , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Mouth/surgery , Retrospective Studies , Surgery, Oral , Young AdultABSTRACT
In a 2010 review in Clinical Pharmacology & Therapeutics, Nick Holford noted that in neonates and young infants, maturation of the organs responsible for drug clearance is a more important determinant of pharmacokinetics (PK) than is body size.(1) Here we review recent developments that provide new insights into how physiological and environmental changes associated with adaptation to extrauterine life affect the ontogeny of drug biotransformation and interpretation of genotype-phenotype relationships in newborns and infants.
Subject(s)
Child Development/physiology , Pharmaceutical Preparations/administration & dosage , Pharmacogenetics/methods , Statistics as Topic/methods , Animals , Aryl Hydrocarbon Hydroxylases/genetics , Aryl Hydrocarbon Hydroxylases/metabolism , Body Size/drug effects , Body Size/physiology , Child Development/drug effects , Cytochrome P-450 CYP2C19 , Genetic Association Studies/methods , Humans , Infant, Newborn , Metabolic Clearance Rate/drug effects , Metabolic Clearance Rate/physiology , Pharmaceutical Preparations/metabolismSubject(s)
Gastroesophageal Reflux/drug therapy , Proton Pump Inhibitors/therapeutic use , Gastroesophageal Reflux/epidemiology , Humans , Infant , Infant, Newborn , Infant, Newborn, Diseases/drug therapy , Off-Label Use/statistics & numerical data , Practice Patterns, Physicians' , Proton Pump Inhibitors/adverse effects , Treatment FailureABSTRACT
BACKGROUND: Bisphosphonates are a class of chemical compounds used in the treatment of a variety of bone-related conditions. Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a well-recognised complication. C-terminal cross-linking telopeptide (CTX) estimation has been suggested as an indicator for the risk of BRONJ. It was reported that values <100 pg/ml represent a high risk of developing BRONJ following surgery and those between 100 and 150 pg/ml, a moderate risk. The aim of this study was to determine the effectiveness of the CTX test in predicting the development of BRONJ. METHODS: This is an 18-month-prospective study of patients taking bisphosphonates, referred to a regional Maxillofacial Surgery Unit for dento-alveolar surgery. The following variables were recorded: age, gender, reason for referral, bisphosphonate type, indication for and duration of bisphosphonate treatment, medical co-morbidities, CTX value, development of BRONJ, and follow-up period. RESULTS: 23 patients underwent a fasting CTX test. The mean age was 59 years (range, 44-78 years). Nineteen were taking alendronic acid, two risedronate sodium and two zoledronic acid. The mean duration of bisphosphonate treatment was 30 months (range, 8-72 months). The mean CTX value was 180 pg/ml (range, 50-370 pg/ml), with 11 patients having a value at or less than 150 pg/ml. The mean follow-up period was 5 months (range, 3-11 months). None of the patients, who underwent removal of one or more teeth, subsequently developed BRONJ. CONCLUSION: The CTX test was not predictive for the development of BRONJ following oral surgery.
Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw/blood , Bone Density Conservation Agents/adverse effects , Collagen Type I/blood , Diphosphonates/adverse effects , Peptides/blood , Adult , Aged , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Tooth Extraction/adverse effectsSubject(s)
Pharmacology, Clinical/trends , Translational Research, Biomedical/trends , Delivery of Health Care , Molecular Biology , National Institutes of Health (U.S.) , Pharmacology, Clinical/legislation & jurisprudence , Translational Research, Biomedical/legislation & jurisprudence , United StatesABSTRACT
The aim of orthognathic surgery is to produce a more aesthetic facial skeletal appearance, and improve jaw function. This prospective study, aimed to evaluate the impact of orthognathic surgery on quality of life for patients with dentofacial deformity, and whether it was clinically meaningful. 62 consecutive patients were recruited (27 male, 35 female) aged 18-38 years. Baseline data were collected using a validated health status measure (Orthognathic Quality of Life Questionnaire (OQLQ)) and a visual analogue scale (VAS). Postoperative questionnaires (OQLQ, VAS) and a Global Transition Scale (GTS) were completed at 6 months after completion of treatment and compared with pre-treatment scores. Following surgery, there was a significant (p<0.05, paired t test) improvement in OQLQ scores for each domain. The proportion of patients reporting a moderate or large improvement was: facial appearance (93%), chewing function (64%), comfort (60%) and speech (32%). Clinical relevance of change scores was reported in terms of effect sizes, and the largest effect was on facial aesthetics. The clinical impact was moderate on social aspects of deformity and oral function and a small effect on awareness of facial deformity. This research reaffirms that orthognathic surgery has positive effects on quality of life.
Subject(s)
Jaw Abnormalities/psychology , Mandible/surgery , Maxilla/surgery , Orthognathic Surgical Procedures/psychology , Quality of Life/psychology , Adolescent , Adult , Combined Modality Therapy , Female , Humans , Jaw Abnormalities/surgery , Longitudinal Studies , Male , Mandible/abnormalities , Maxilla/abnormalities , Oral Surgical Procedures/methods , Oral Surgical Procedures/psychology , Orthodontics, Corrective/psychology , Orthognathic Surgical Procedures/methods , Treatment Outcome , Young AdultABSTRACT
INTRODUCTION: Systemic lupus erythematosus (SLE) is an auto-immune disease that is characterised by autoantibody production. Male lupus is rare, apart from at either end of the age spectrum. AIM: In this series, we review the histories of six male lupus patients attending our service. RESULTS: Our patients presented in middle age and tended to develop haematological abnormalities, renal involvement and neurological manifestations which preceded the onset of their skin and joint complaints. Our patients accrued damage rapidly and overall did badly. They tended to respond sub-optimally to standard treatments. These cases highlight the need an increased awareness that male SLE patients present with a wide variety of symptoms, and that they accrue damage quickly. There is a need for timely diagnosis and appropriate initiation of treatment. This may help avoid preventable organ damage and increase the survival of men with SLE.
Subject(s)
Lupus Erythematosus, Systemic/diagnosis , Adult , Aged , Fatal Outcome , Glucocorticoids/administration & dosage , Humans , Lupus Erythematosus, Systemic/drug therapy , Male , Middle Aged , Prednisolone/administration & dosageABSTRACT
Any health-care provider knows that the sneezing, wheezing, and itching that are commonplace most often involve a small molecule, namely, histamine. In addition to its inherent physiologic role, this seemingly small "actor" is of profound historical and fiscal significance. This is evidenced in part by the awarding of the 1936 Nobel Prize in physiology or Medicine to Sir Henry Hallett Dale and Dr Otto Loewi who discovered the actions of histamine and the 1957 Nobel Prize in physiology or medicine to pharmacologist Dr Daniel Bovet who discovered the first antihistamine, pyrilamine (neoantergan)(1). (see Supplementary Data for full reference).