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Clinical Medicine (London, England) Oct 2018A 69-year-old man developed reduced consciousness of sudden onset. Examination and parameters were normal, except for a Glasgow Coma Scale (GCS) score of six. Brain... (Review)
Review
A 69-year-old man developed reduced consciousness of sudden onset. Examination and parameters were normal, except for a Glasgow Coma Scale (GCS) score of six. Brain imaging and blood tests were also normal, except for high plasma ammonia. His past medical history included epilepsy, hypertension and colitis. He was taking multiple antiepileptic medications, including sodium valproate, with no recent dose alterations. Medical intervention led to the sodium valproate being stopped and naloxone being administered. The patient's level of responsiveness and ammonia levels gradually improved. The patient was also being treated with ciprofloxacin for a urinary tract infection and a newly developed syndrome of inappropriate antidiuretic hormone secretion treated with demeclocycline. There is an association between long-term sodium valproate use and low carnitine levels, especially in the setting of polypharmacy. This in turn precipitates hyperammonaemia and encephalopathy. This case highlights the importance of an adequate drug history and the awareness of serious but uncommon adverse effects.
Topics: Aged; Ammonia; Anticonvulsants; Brain Diseases; Carnitine; Consciousness Disorders; Epilepsy; Humans; Hyperammonemia; Male; Polypharmacy; Valproic Acid
PubMed: 30287443
DOI: 10.7861/clinmedicine.18-5-430 -
Cureus May 2018We present the case of a 55-year-old Caucasian male with a history of schizophrenia presenting with severe hyponatremia attributed to long-acting injectable risperidone...
We present the case of a 55-year-old Caucasian male with a history of schizophrenia presenting with severe hyponatremia attributed to long-acting injectable risperidone treatment. Antipsychotic-induced hyponatremia is an uncommon but serious side effect that should be considered when assessing individuals on chronic psychiatric regimens. In this report, we will discuss our treatment plan for the patient when water deprivation and hypertonic saline failed to correct his serum sodium levels. The goal of this case report is to raise awareness of severe hyponatremia as a side effect of long-acting risperidone, and to encourage further studies to create guidelines for its management when current protocols fail to correct sodium levels.
PubMed: 30042908
DOI: 10.7759/cureus.2657 -
European Endodontic Journal 2018Tetracyclines are a unique class of antibiotics which also have additional effects including anti-inflammatory, anti-resorptive and substantive within the root canal.... (Review)
Review
Tetracyclines are a unique class of antibiotics which also have additional effects including anti-inflammatory, anti-resorptive and substantive within the root canal. There has been a long-held view that tetracycline medicaments discolour teeth and should be avoided. The evidence base around this topic was explored, including a review of the methodology used in laboratory studies. A search of PubMed, Medline and Scopus databases was conducted to identify studies of demeclocycline and doxycycline medicaments used in root canal therapy. An analysis of the methodology used in these studies was performed to determine if these replicate current clinical practice. The related literature on mechanisms of tetracycline stability and the effects of light, oxidation, moisture and chemical interactions was examined. Studies investigating the effects of Ledermix paste on segments of bovine dentine and avulsed or reimplanted teeth as well as combinations with other antibiotics were excluded from this review. Even though demeclocycline medicament pastes were introduced in 1962, the first laboratory studies of discolouration were not done until 2000. All later studies followed a similar approach, which included exposure to sodium hypochlorite for up to 30 minutes and storage in moist conditions with 100% humidity. Staining during dark storage and enhanced staining on exposure to light were reported, indicating multiple pathways of degradation of demeclocycline and its reaction products. Light, moisture and oxidation are the key factors which drive discolouration from demeclocycline. Clinical issues from tooth staining can be prevented by removal of medicament pastes from the access cavity, and placement of a sound interim restoration. Use of a doxycycline paste obviates concerns of staining. Laboratory assessments of the potential for staining should replicate in vivo conditions.
PubMed: 32161858
DOI: 10.14744/eej.2018.47966 -
The Cochrane Database of Systematic... Jun 2018Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs frequently, can be caused by various conditions, and is associated with shorter survival and longer... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs frequently, can be caused by various conditions, and is associated with shorter survival and longer hospital stays. Many treatments, such as fluid restriction or vasopressin receptor antagonists can be used to improve the hyponatraemia, but whether that translates into improved patient-important outcomes is less certain.
OBJECTIVES
This review aimed to 1) look at the benefits and harms of interventions for chronic non-hypovolaemic hypotonic hyponatraemia when compared with placebo, no treatment or head-to-head; and 2) determine if benefits and harms vary in absolute or relative terms dependent on the specific compound within a drug class, on the dosage used, or the underlying disorder causing the hyponatraemia.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 1 December 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We also screened the reference lists of potentially relevant studies, contacted authors, and screened the websites of regulatory agencies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of any intervention with placebo, no treatment, standard care, or any other intervention in patients with chronic non-hypovolaemic hypotonic hyponatraemia. We also included subgroups with hyponatraemia from studies with broader inclusion criteria (e.g. people with chronic heart failure or people with cirrhosis with or without hyponatraemia), provided we could obtain outcomes for participants with hyponatraemia from the report or the study authors.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed risk of bias. We expressed treatment effects as mean difference (MD) for continuous outcomes (health-related quality of life, length of hospital stay, change from baseline in serum sodium concentration, cognitive function), and risk ratio (RR) for dichotomous outcomes (death, response and rapid increase in serum sodium concentration, hypernatraemia, polyuria, hypotension, acute kidney injury, liver function abnormalities) together with 95% confidence intervals (CI).
MAIN RESULTS
We identified 35 studies, enrolling 3429 participants. Twenty-eight studies (3189 participants) compared a vasopressin receptor antagonist versus placebo, usual care, no treatment, or fluid restriction. In adults with chronic, non-hypovolaemic hypotonic hyponatraemia, vasopressin receptor antagonists have uncertain effects on death at six months (15 studies, 2330 participants: RR 1.11, 95% CI 0.92 to 1.33) due to risk of selective reporting and serious imprecision; and on health-related quality of life because results are at serious risk of performance, selective reporting and attrition bias, and suffer from indirectness related to the validity of the Short Form Health Survey (SF-12) in the setting of hyponatraemia. Vasopressin receptor antagonists may reduce hospital stay (low certainty evidence due to risk of performance bias and imprecision) (3 studies, 610 participants: MD -1.63 days, 95% CI -2.96 to -0.30), and may make little or no difference to cognitive function (low certainty evidence due to indirectness and imprecision). Vasopressin receptor antagonists probably increase the intermediate outcome of serum sodium concentration (21 studies, 2641 participants: MD 4.17 mmol/L, 95% CI 3.18 to 5.16), corresponding to two and a half as many people having a 5 to 6 mmol/L increase in sodium concentration compared with placebo at 4 to 180 days (moderate certainty evidence due to risk of attrition bias) (18 studies, 2014 participants: RR 2.49, 95% CI 1.95 to 3.18). But they probably also increase the risk of rapid serum sodium correction - most commonly defined as > 12 mmol/L/d (moderate certainty evidence due to indirectness) (14 studies, 2058 participants: RR 1.67, 95% CI 1.16 to 2.40) and commonly cause side-effects such as thirst (13 studies, 1666 participants: OR 2.77, 95% CI 1.80 to 4.27) and polyuria (6 studies, 1272 participants): RR 4.69, 95% CI 1.59 to 13.85) (high certainty evidence). The potential for liver toxicity remains uncertain due to large imprecision. Effects were generally consistent across the different agents, suggesting class effect.Data for other interventions such as fluid restriction, urea, mannitol, loop diuretics, corticosteroids, demeclocycline, lithium and phenytoin were largely absent.
AUTHORS' CONCLUSIONS
In people with chronic hyponatraemia, vasopressin receptor antagonists modestly raise serum sodium concentration at the cost of a 3% increased risk of it being rapid. To date there is very low certainty evidence for patient-important outcomes; the effects on mortality and health-related quality of life are unclear and do not rule out appreciable benefit or harm; there does not appear to be an important effect on cognitive function, but hospital stay may be slightly shorter, although available data are limited. Treatment decisions must weigh the value of an increase in serum sodium concentration against its short-term risks and unknown effects on patient-important outcomes. Evidence for other treatments is largely absent.Further studies assessing standard treatments such as fluid restriction or urea against placebo and one-another would inform practice and are warranted. Given the limited available evidence for patient-important outcomes, any study should include these outcomes in a standardised manner.
Topics: Antidiuretic Hormone Receptor Antagonists; Chronic Disease; Humans; Hyponatremia; Length of Stay; Quality of Life; Randomized Controlled Trials as Topic; Sodium
PubMed: 29953167
DOI: 10.1002/14651858.CD010965.pub2 -
PloS One 2018Antimicrobial photodynamic inactivation (aPDI) employs photosensitizing dyes activated by visible light to produce reactive oxygen species. aPDI is independent of the...
Antimicrobial photodynamic inactivation (aPDI) employs photosensitizing dyes activated by visible light to produce reactive oxygen species. aPDI is independent of the antibiotic resistance status of the target cells, and is thought unlikely to produce resistance itself. Among many PS that have been investigated, tetracyclines occupy a unique niche. They are potentially dual-action compounds that can both kill bacteria under illumination, and prevent bacterial regrowth by inhibiting ribosomes. Tetracycline antibiotics are regarded as bacteriostatic rather than bactericidal. Doxycycline (DOTC) is excited best by UVA light (365 nm) while demeclocycline (DMCT) can be efficiently activated by blue light (415 nm) as well as UVA. Both compounds were able to eradicate Gram-positive (methicillin-resistant Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria (>6 log(10) steps of killing) at concentrations (10-50μM) and fluences (10-20J/cm2). In contrast to methylene blue, MB plus red light, tetracyclines photoinactivated bacteria in rich growth medium. When ~3 logs of bacteria were killed with DMCT/DOTC+light and the surviving cells were added to growth medium, further bacterial killing was observed, while the same experiment with MB allowed complete regrowth. MIC studies were carried out either in the dark or exposed to 0.5mW/cm2 blue light. Up to three extra steps (8-fold) increased antibiotic activity was found with light compared to dark, with MRSA and tetracycline-resistant strains of E. coli. Tetracyclines can accumulate in bacterial ribosomes, where they could be photoactivated with blue/UVA light producing microbial killing via ROS generation.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Escherichia coli; Light; Methicillin-Resistant Staphylococcus aureus; Methylene Blue; Microbial Sensitivity Tests; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Ribosomes; Tetracyclines
PubMed: 29742128
DOI: 10.1371/journal.pone.0196485 -
Australian Dental Journal Jun 2018Many studies have investigated the effectiveness of root canal irrigants and medicaments against Enterococcus faecalis. The aim of this study was to compare the efficacy... (Comparative Study)
Comparative Study
BACKGROUND
Many studies have investigated the effectiveness of root canal irrigants and medicaments against Enterococcus faecalis. The aim of this study was to compare the efficacy of commonly used medicaments against E. faecalis cultured as a biofilm on dentine substrate.
METHODS
An E. faecalis biofilm was established on human dentine slices using a continuous flow cell. Each test medicament (Ledermix, Ca(OH) , Odontopaste, 0.2% chlorhexidine and 50:50 combinations of Ledermix/Ca(OH) and Odontopaste/Ca(OH) ) was introduced into the flow cell and biofilms were harvested and quantitated by determining cellular protein. Cellular viability was determined using serial plating and the number of colony-forming units was normalized against cellular protein to allow treatment protocols to be compared. Qualitative scanning electron microscopy analyses of the biofilm were performed after a 48-h exposure to each test agent.
RESULTS
Sodium hypochlorite achieved total bacterial elimination. Ledermix and Odontopaste had no significant effect on the E. faecalis biofilm. Ca(OH) and 50:50 combinations of Ca(OH) /Ledermix or Ca(OH) /Odontopaste reduced the viability by more than 99% while 0.2% chlorhexidine reduced bacterial numbers by 97%.
CONCLUSIONS
Sodium hypochlorite remains the gold standard for bacterial elimination in root canal therapy. However, Ca(OH) in isolation and combined with Ledermix, and Odontopaste was highly effective in reducing bacterial viability.
Topics: Biofilms; Calcium Hydroxide; Chlorhexidine; Demeclocycline; Dental Pulp Cavity; Dentin; Drug Combinations; Enterococcus faecalis; Humans; Microbial Viability; Microscopy, Electron, Scanning; Root Canal Irrigants; Sodium Hypochlorite; Triamcinolone Acetonide
PubMed: 29181844
DOI: 10.1111/adj.12580 -
Acta Biochimica Et Biophysica Sinica Dec 20176-Demethylchlortetracycline (6-DCT), a tetracycline antibiotic produced by Streptomyces aureofaciens, is a crucial precursor employed for the semi-synthesis of...
6-Demethylchlortetracycline (6-DCT), a tetracycline antibiotic produced by Streptomyces aureofaciens, is a crucial precursor employed for the semi-synthesis of tigecycline, minocycline, and amadacyclin (PTK 0796). In this study, the 6-DCT biosynthetic gene cluster (BGC) was cloned from genomic DNA of a high 6-DCT-producing strain, S. aureofaciens DM-1, using the transformation-associated recombination method. An extra copy of the 6-DCT BGC was introduced and integrated into the chromosome of S. aureofaciens DM-1. Duplication of the 6-DCT BGC resulted in a maximum increase of the 6-DCT titer by 34%.
Topics: Anti-Bacterial Agents; Demeclocycline; Multigene Family; Recombination, Genetic; Streptomyces aureofaciens
PubMed: 29087452
DOI: 10.1093/abbs/gmx110 -
Journal of Clinical Research in... Sep 2017Hyponatremia is the most common electrolyte disorder among hospitalized patients and it is sometimes considered as a poor outcome predictor. Its correction is thus... (Review)
Review
Hyponatremia is the most common electrolyte disorder among hospitalized patients and it is sometimes considered as a poor outcome predictor. Its correction is thus indicated, even in asymptomatic patients. The conventional treatment consists of fluid restriction in presence of euvolemia or hypervolemia; loop diuretics are used in some hypervolemic conditions such as cardiac heart failure, liver cirrhosis and nephrotic syndrome, while intravenous isotonic or hypertonic solutions are administered in hypovolemic conditions. The utilization of demeclocycline and urea is not indicated in pediatric ages due to lack of data on their toxicity and poor tolerance. Recently, a new therapeutic option has been developed, a class of non-peptide arginine vasopressin receptor antagonists called vaptans. Tolvaptan is the only such agent approved in Europe for the treatment of hyponatremia caused by syndrome of inappropriate antidiuretic hormone secretion (SIADH) in adults. In USA, tolvaptan and conivaptan have been approved for treatment of euvolemic and hypervolemic hyponatremia. Few data are so far available in paediatric patients, since only one trial has been registered in Europe which includes children and adolescents, but this trial is still ongoing. Here, we report three children with chronic hyponatremia due to SIADH in which tolvaptan has been used successfully.
Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Child; Child, Preschool; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Tolvaptan
PubMed: 28515029
DOI: 10.4274/jcrpe.4531 -
Oncotarget Dec 2016Generalized arterial calcification of infancy (GACI) is an autosomal recessive disorder characterized by early onset of extensive mineralization of the cardiovascular... (Comparative Study)
Comparative Study
Generalized arterial calcification of infancy (GACI) is an autosomal recessive disorder characterized by early onset of extensive mineralization of the cardiovascular system. The classical forms of GACI are caused by mutations in the ENPP1 gene, encoding a membrane-bound pyrophosphatase/phosphodiesterase that hydrolyzes ATP to AMP and inorganic pyrophosphate. The asj-2J mouse harboring a spontaneous mutation in the Enpp1 gene has been characterized as a model for GACI. These mutant mice develop ectopic mineralization in skin and vascular connective tissues as well as in cartilage and collagen-rich tendons and ligaments. This study examined in detail the temporal ectopic mineralization phenotype of connective tissues in this mouse model, utilizing a novel cryo-histological method that does not require decalcification of bones. The wild type, heterozygous, and homozygous mice were administered fluorescent mineralization labels at 4 weeks (calcein), 10 weeks (alizarin complexone), and 11 weeks of age (demeclocycline). Twenty-four hours later, outer ears, muzzle skin, trachea, aorta, shoulders, and vertebrae were collected from these mice and examined for progression of mineralization. The results revealed differential timeline for disease initiation and progression in various tissues of this mouse model. It also highlights the advantages of cryo-histological fluorescent imaging technique to study mineral deposition in mouse models of ectopic mineralization disorders.
Topics: Animals; Anthraquinones; Connective Tissue; Demeclocycline; Disease Progression; Fluoresceins; Fluorescent Dyes; Genetic Predisposition to Disease; Heterozygote; Homozygote; Mice, Inbred BALB C; Mice, Mutant Strains; Microscopy, Fluorescence; Mutation; Phenotype; Phosphoric Diester Hydrolases; Pyrophosphatases; Time Factors; Vascular Calcification
PubMed: 27863377
DOI: 10.18632/oncotarget.13335 -
Endocrine Feb 2017The syndrome of inappropriate antidiuresis is often undertreated with most patients discharged with persistent hyponatraemia. This study tested the hypothesis that an...
Improving care and outcomes of inpatients with syndrome of inappropriate antidiuresis (SIAD): a prospective intervention study of intensive endocrine input vs. routine care.
PURPOSE
The syndrome of inappropriate antidiuresis is often undertreated with most patients discharged with persistent hyponatraemia. This study tested the hypothesis that an endocrine input is superior to routine care in correcting hyponatraemia and can improve patient outcomes.
METHODS
This single-centre prospective-controlled intervention study included inpatients admitted at a UK teaching hospital, with serum sodium ≤ 127 mmol/l, due to syndrome of inappropriate antidiuresis over a 6-month period. The prospective intervention group (18 subjects with mean serum sodium 120.7 mmol/l) received prompt endocrine input, while the historical control group (23 patients with mean serum sodium 124.1 mmol/l) received routine care. The time needed for serum sodium increase ≥ 5 mmol/l was the primary endpoint.
RESULTS
The intervention group achieved serum sodium rise by ≥5 mmol/l in 3.5 vs. 7.1 days in the control group (P = 0.005). In the intervention group, the mean total serum sodium increase was 12 mmol/l with only 5.8 % of patients discharged with serum sodium < 130 vs. 6.3 mmol/l increase (P < 0.001) and 42.1 % of the subjects discharged with serum sodium < 130 mmol/l in the control group (P = 0.012). The mean length of hospital stay in the intervention group (10.9 days) was significantly shorter than in the control group (14.5 days; P = 0.004).The inpatient mortality rate was 5.5 % in intervention arm vs. 17.4 % in control arm, but this difference was not statistically significant.
CONCLUSIONS
Since the endocrine input improved time for correction of hyponatraemia and shortened length of hospitalisation, widespread provision of endocrine input should be considered.
Topics: Aged; Aged, 80 and over; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Demeclocycline; Female; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Prospective Studies; Retrospective Studies; Saline Solution, Hypertonic; Sodium; Tolvaptan; Treatment Outcome
PubMed: 27837439
DOI: 10.1007/s12020-016-1161-9