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Biomedical subjects

Alan Jones

Publications and source records attributed to Alan Jones.

14 recordsLinked to original sources

Evaluating the return of additional findings from the 100,000 Genomes Project: A mixed-methods study exploring participant experiences of receiving secondary findings from genomic sequencing.

PURPOSE: The 100,000 Genomes Project participants could consent to receive additional findings (AFs) for variants associated with susceptibility to cancer and familial hypercholesterolemia. Here, we evaluate stakeholder experiences to inform clinical practice. METHODS: Mixed-methods study conducted at 18 sites across England that comprised a cross-sectional survey and interviews with participants who received a positive AF (PAF) and interviews with participants who had no AFs (NAF). RESULTS: There were 146 surveys followed by 35 interviews with PAF participants and 29 interviews with NAF participants. Surveys found that PAF results were seen as useful and would influence health management (82%). Most (90%) had shared their result with family members. Experiences differed by PAF type; cancer PAF participants were often initially shocked and anxious and found telling family members challenging compared with participants with a familial hypercholesterolemia PAF. Although most experiences of NAF results were positive, some misunderstandings were identified. Participants supported returning AFs when offering genome sequencing. CONCLUSION: Patient experiences of receiving AFs were primarily positive, and there is support for offering AFs routinely. Considerations for offering AFs in clinical practice include adapting approaches tailored to individual conditions and greater support for people with a NAF result.

Humans↗

Physical properties of root cementum: Part 9. Effect of systemic fluoride intake on root resorption in rats.

INTRODUCTION: Orthodontically induced inflammatory root resorption is a common complication in orthodontic treatment. Fluoride has been reported to have a beneficial effect against root resorption in dental traumatology. The effect of fluoride on orthodontically induced inflammatory root resorption has not been investigated. This study was undertaken to investigate the effect of fluoride on the incidence of root resorption. METHODS: Thirty-two female 8-week-old Wistar rats were separated into 4 groups. Two groups (6 rats per group) were controls; they did not undergo orthodontic tooth movement. The other 2 groups (10 rats per group) had orthodontic tooth movement consisting of activated 100-g closing nickel-titanium coils (NiTi 10-000-06, GAC International, Bohemia, NY) connecting the mandibular first molar to the incisors. Fluoridated water (100 ppm) was given ad libitum to 1 control and 1 experimental group. The other 2 groups received deionized water. After 2 weeks, the animals were killed, and the samples were harvested. Resorption craters were scanned with a Micro CT (SkyScan 1072, Aartselaar, Belgium). Software analysis of the scanned samples provided a volumetric measurement of the resorption craters on the mandibular molar cementum surface. RESULTS: Resorption sites were found in the control samples, especially on the distal surfaces; this could be attributed to normal physiological tooth drift. Resorption sites were significantly (P <.05) increased in the groups receiving orthodontic tooth movement. CONCLUSIONS: Fluoride reduces the size of resorption craters, but the effect is variable and not statistically significant (P >.05).

Administration, Oral↗

Ventricular tachycardia associated with hereditary magnesium-losing nephropathy.

Ventricular tachycardia (VT) can be a life threatening condition which can be caused by an underlying electrolyte disturbance, such as hypomagnesaemia. Causes of electrolyte disturbances, such as magnesium losing nephropathy, should be identified early to allow correct management of the underlying cause of the cardiac arrhythmia.

Adult↗

Recombinant human bone morphogenetic protein-2 in open tibial fractures. A subgroup analysis of data combined from two prospective randomized studies.

BACKGROUND: The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) to improve the healing of open tibial shaft fractures has been the focus of two prospective clinical studies. The objective of the current study was to perform a subgroup analysis of the combined data from these studies. METHODS: Two prospective, randomized clinical studies were conducted. A total of 510 patients with open tibial fractures were randomized to receive the control treatment (intramedullary nail fixation and routine soft-tissue management) or the control treatment and an absorbable collagen sponge impregnated with one of two concentrations of rhBMP-2. The rhBMP-2 implant was placed over the fracture at the time of definitive wound closure. For the purpose of this analysis, only the control treatment and the Food and Drug Administration-approved concentration of rhBMP-2 (1.50 mg/mL) were compared. Patients who anticipated receiving planned bone-grafting as part of a staged treatment were excluded from enrollment. RESULTS: Fifty-nine trauma centers in twelve countries participated, and patients were followed for twelve months postoperatively. Two subgroups were analyzed: (1) the 131 patients with a Gustilo-Anderson type-IIIA or IIIB open tibial fracture and (2) the 113 patients treated with reamed intramedullary nailing. The first subgroup demonstrated significant improvements in the rhBMP-2 group, with fewer bone-grafting procedures (p = 0.0005), fewer patients requiring invasive secondary interventions (p = 0.0065), and a lower rate of infection (p = 0.0234), compared with the control group. The second subgroup analysis of fractures treated with reamed intramedullary nailing demonstrated no significant difference between the control and the rhBMP-2 groups. CONCLUSIONS: The addition of rhBMP-2 to the treatment of type-III open tibial fractures can significantly reduce the frequency of bone-grafting procedures and other secondary interventions. This analysis establishes the clinical efficacy of rhBMP-2 combined with an absorbable collagen sponge implant for the treatment of these severe fractures.

Absorbable Implants↗

Reinnervation of laryngeal muscles: a study of changes in myosin heavy chain expression.

Direct repair of the recurrent laryngeal nerve (RLN) results in synkinesis and compromised laryngeal function. We have therefore developed a pig model to investigate whether anastomosis of the phrenic nerve with the abductor branch of the RLN leads to specific reinnervation of abductor muscles. Expression of myosin heavy chain protein (MyHC), a marker of appropriate reinnervation, was determined in the posterior cricoarytenoid (PCA) abductor and thyroarytenoid (TA) adductor muscles following nerve injury and repair. The denervated PCA muscle exhibited decreased levels of the fast-type MyHC isoforms IIA and IIB, and increased slow-type MyHC expression. Similarly, there was a fall in type IIB levels in the denervated TA muscle but increases in both IIA and slow MyHC. Four months after repair, the MyHC expression in the PCA was near normal, suggesting that our model reduces the risk of synkinesis and ensures the accurate muscle reinnervation required for full functional recovery.

Analysis of Variance↗

An ex vivo model for reperfusion of laryngotracheal grafts.

OBJECTIVE: To describe the development of an ex vivo model to facilitate the study of ischemia-reperfusion injury in laryngotracheal grafts taken from Minnesota minipigs. STUDY DESIGN: This is a descriptive study. METHODS: Laryngotracheal grafts from Minnesota minipigs were harvested and placed in cold storage for 3 hours. Autologous blood was used to reperfuse the graft for up to 8 hours using the described reperfusion model. RESULTS: By altering retrieval technique and pressures within the graft, we demonstrated healthy grafts after 8 hours of reperfusion. CONCLUSIONS: Ex vivo reperfusion offers a range of experimental advantages over in vivo reperfusion including close control of interventions, ease of outcome measurement, and reduction in animal use. This model is now ready to be used for further studies of interventions to reduce ischemia-reperfusion injury in these grafts.

Animals↗

Guidelines for the provision of echocardiography in Canada: recommendations of a joint Canadian Cardiovascular Society/Canadian Society of Echocardiography Consensus Panel.

Recognizing the central role of echocardiographic examinations in the assessment of most cardiac disorders and the need to ensure the provision of these services in a highly reliable, timely, economical and safe manner, the Canadian Cardiovascular Society and Canadian Society of Echocardiography undertook a comprehensive review of all aspects influencing the provision of echocardiographic services in Canada. Five regional panels were established to develop preliminary recommendations in the five component areas, which included the echocardiographic examination, the echocardiographic laboratory and report, the physician, the sonographer and indications for examinations. Membership in the panels was structured to recognize the regional professional diversity of individuals involved in the provision of echocardiography. In addition, a focus group of cardiac sonograhers was recruited to review aspects of the document impacting on sonographer responsibilities and qualification. The document is intended to be used as a comprehensive and practical reference for all of those involved in the provision of echocardiography in Canada.

Canada↗

Laryngeal abductor muscle reinnervation in a pig model.

OBJECTIVE: To develop a large animal model for studies of laryngeal abductor reinnervation. MATERIAL AND METHODS: Six minipigs underwent unilateral anastomosis of the phrenic nerve-abductor branch of the recurrent laryngeal nerve (RLN). Polyhydroxybutyrate (PHB) conduits were used for repair. At each of 30, 60 and 120 days, 2 animals underwent video laryngeal endoscopy (VLE) and were then killed. VLE was also performed in the 120-day pair at 60 days. Nerve-conduit-nerve-muscle samples were fixed for light and immunofluorescence (pan-neurofilaments, S-100) microscopy. Laryngeal muscles were harvested (myosin heavy chain analysis). RESULTS: VLE showed recovery of abductor function in 1 animal at 60 days and in 1 at 120 days. Haematoxylin-eosin staining demonstrated a complex inflammatory response. Eosinophil recruitment was observed. Stepwise regeneration and reorganization of the distal nerve between 30 and 120 days was observed with pan-NF staining. The mean minimum diameter in the reinnervated posterior crico-arytenoids tended to increase for up to 120 days. CONCLUSIONS: Anastomosis of the phrenic nerve-abductor branch of the RLN with a PHB conduit in a pig can result in functional and histological recovery within 2-4 months and appears to at least sustain abductor muscle fibre morphology. Recovery occurs despite a complex inflammatory response, which may be an essential part of healing rather than inhibitory.

Anastomosis, Surgical↗

Overview of SHOT hardware capabilities and range of cell biology experiment designs.

Cell science hardware is currently available for lease or production by SHOT(R). The SHOT Avian Development Facility (ADF) is a single middeck locker experiment containing two carousels capable of rotating at variable g. Each carousel accommodates 18 40-ml vessels that can be adapted for the cultivation of avian or reptilian eggs, small invertebrates, zebra fish, small plants, seeds, spores, cells or tissues. Cellcult Cassettes contain a small (20-50 ml) rotating cylindrical culture vessel with feed media reservoir, pumps, waste bag and sample collection bags. Cultures can be rotated, perfused, fed, aerated and sampled automatically or on remote command. Fluid Processing Cassettes contain a flexible combination of feed, culture and fixative bags with valves and pumps programmable for various feeding and fixing protocols. Dynacult Cassettes contain a cylindrical bioreactor with differentially rotating walls, pumps and valves for feeding and sampling, and pH and oxygen measurement. All cassettes are doubly contained and are accommodated by a computerized, thermally controlled processing facility, the Advanced Space Experiment Processor, which processes three cassettes, or the Biotechnology Thermal Environment Carrier, which holds up to six cassettes.

Animals↗

Daily multidisciplinary rounds shorten length of stay for trauma patients.

PURPOSE: Efficient patient care depends on close communication between the trauma team, other surgical providers, nursing, physical therapy, and discharge planners. Communication is hampered by the number of services involved, the workload of each service, and the institution's training mission. We hypothesized that daily multidisciplinary "discharge rounds" would improve patient flow and increase readiness. METHODS: A senior trauma center physician leads discharge rounds, focusing on each patient's plan of care, including surgeries, diagnostic tests, and anticipated date of discharge or transfer. Present at rounds are the fellows leading each trauma team; an orthopedic surgeon; the hospital bed manager; the unit's discharge planner; the unit nursing staff; and physical, occupational, and speech therapists. RESULTS: Discharge rounds cover 90 inpatient trauma service beds in approximately 60 minutes each day. Discharge rounds have had a dramatic effect on patient flow. While maintaining the daily census, we have seen a 36% increase in patient volume and a 15% decrease in length of stay. "Bypass" status-inability to accept admissions-has been virtually eliminated. This effect has been sustained. CONCLUSION: By providing a forum for clear communications among all providers, discharge rounds have streamlined the care of complex trauma patients. As health care resources become ever more constrained, this sort of multidisciplinary effort is a viable option for senior physicians to directly impact hospital performance.

Humans↗

Effect of the counter-anion type and concentration on the liquid chromatography retention of beta-blockers.

Analysis of beta-blockers, basic pharmaceutical compounds with pKa values greater than 8.5, in reversed-phase HPLC can sometimes be challenging in terms of selection of the mobile phase pH, buffer concentration, and acidic modifier. The effect of the type and concentration of various mobile phase additives on the reversed-phase HPLC retention of these compounds was studied. HPLC analysis was performed at a mobile phase pH of 3 ensuring the protonation of the beta-blockers. It was found that at increasing perchlorate anion concentration at a constant mobile phase pH the retention factor for all beta-blocker compounds studied increased to varying degrees. The relative increase in the retention was attributed to ion interaction with the anionic mobile phase additive. Similar trends were observed when other types of inorganic salts such as NaH2PO4, NaPF6, NaBF4, and CF3CO2Na were employed. Differences in selectivity of the beta-blockers were obtained at a constant pH and an equimolar concentration of the different additives throughout the whole concentration range studied.

Adrenergic beta-Antagonists↗

Development of a competitive immunoassay for the determination of N-(2-hydroxyethyl)valine adducts in human haemoglobin and its application in biological monitoring.

Ethylene oxide (EO) is an important industrial compound and a directly acting mutagen. Human exposure to it can be monitored by the determination of haemoglobin (Hb) adducts. An immunoassay that quantifies the N-terminal adduct N-(2-hydroxyethyl)valine in whole blood was developed, and its potential usefulness as a tool for biologically monitoring occupational exposure demonstrated. Analytical reliability was confirmed in a comparative study with gas chromatography-mass spectrometry (range 0.040-589 nmol g(-1) Hb, correlation coefficient 0.98, n=10). The assay was configured as a competitive enzyme-linked immunosorbent assay to facilitate the rapid throughput of samples. The assay uses a whole blood matrix and has a working range of 10-10000 pmol N-(2-hydroxyethyl)valine g(-1) hB. The assay does not appear to be affected by structurally similar metabolites and has been used to determine adducts in human blood samples. The first results from potentially exposed workers indicate the assay might be a powerful tool for the routine occupational biomonitoring of EO exposure.

Binding, Competitive↗