High dose semaglutide carries higher associated risk profile

AimsThe aim of this audit was to look into patients on high dose antipsychotics who had developed complications of constipation in the PICU setting .BackgroundAntipsychotics are usually used in the treatment of Schizophrenia and other psychotic illnesses. Drug such as Clozapine mainly has a higher risk profile due to gastrointestinal hypo motility. It could present as constipation, fecal impaction or a bowel obstruction and could even lead to death.MethodDuring ward rounds enquired on bowel habits and diet.Physical examination of patients complaining of abdominal pain.Screened notes in past to see how many patients complained of constipation and interventions suggested and used.I65.Result3 of the 10 patients on PICU were on high dose antipsychotics and 2 of them had reported constipation. Of which one required daily review and vigorous treatment with laxatives and dietary changes.RecommendationBristol stool chart introduced as part of care plan for all patients.Teaching presentation of constipation and its treatment management was given to the PICU team.Involving medical team early on for assessment and prophylactic laxatives prescription.Liaison with the pantry team to include more options of fruits and vegetables into daily meal plan for patients.Data and material handed over to next trainee to Re-audit and complete audit cycle.ConclusionAppropriate prevention and early management of side effects can enhance the benefits of antipsychotics. Bowel function monitoring and the use of prophylactic laxatives for patient on high dose antipsychotics such as clozapine is advisable to prevent complications related to it.

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DNMT3A Mutations In AML: Incidence, Prognostic Influence and Association With Other Molecular Markers

Blood ◽

10.1182/blood.v122.21.2627.2627 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2627-2627

Author(s):

Igor Wolfgang Blau ◽

Rimma Berenstein ◽

Claudia D. Baldus ◽

Sophie Schlabitz ◽

Asiye Kar ◽

...

Keyword(s):

Dna Methyltransferase ◽

Median Overall Survival ◽

Conflicts Of Interest ◽

Direct Sequencing ◽

Risk Profile ◽

High Dose ◽

Intermediate Risk ◽

Recurrent Mutations ◽

Idh1 And Idh2 Mutations ◽

Highly Correlated

Abstract Abnormal epigenetic regulation has been implicated in oncogenesis. Mutations in the DNA methyltransferase 3A (DNMT3A) gene were recently demonstrated in acute myeloid leukemia (AML) as a candidate for the initiating of lesions in AML with adverse clinical outcome. Using direct sequencing, identification of the DNMT3A mutations was done in 320 AML patients. Additionally, we analyzed NPM1, FLT3-ITD, FLT3-D835, IDH1 and IDH2 mutations by PCR and DNA sequencing. The retrospective analysis of diagnostic bone marrow samples was performed in AML patients treated in our institution. In all AML patients double induction therapy containing of “7+3” therapy followed by 4 cycles of high dose AraC consolidation was implicated in accordance with therapeutic standards of our institution. We identified DNMT3A mutations in 22% of AML patients. The most common of mutations affect amino acid R822 in exon 23. The DNMT3A mutation was highly enriched in the group of patients with intermediate-risk profile (35%, P<0.01). Unlikely FLT3, DNMT3A mutations were absent in all AML patients with favorable-risk group (P<0.001). AML patients with DNMT3A mutations were older (P=0.05), had higher WBC and platelet counts (P=0.02 for both comparison) and higher relapse rate (P=0.01). The median overall survival among AML patients with DNMT3A mutations was significantly shorter than among patients without such mutation (13.3 months versus 31.3 months, P<0.01). Occurrence of DNMT3A mutations was associated with presence of other common mutations, such as NPM1, FLT3-ITD, FLT3-D835, IDH1 and IDH2. Correlations of the DNMT3A mutations with NPM1 and FLT3-ITD mutations were significant (P<0.001). Our results indicate that DNMT3A mutations are highly recurrent in AML patients with intermediate-risk profile. DNMT3A mutations are highly correlated with NPM1/FLT3-ITD mutations and are associated with an unfavorable prognosis. The discovery of recurrent mutations in DNMT3A gene may provide a new prognostic marker for the risk stratification for AML patients. Disclosures: No relevant conflicts of interest to declare.

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Electron Beam Damage of Biomolecules Assessed by Energy Loss Spectroscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100069855 ◽

1978 ◽

Vol 36 (3) ◽

pp. 61-69

Author(s):

M. Isaacson ◽

M.L. Collins ◽

M. Listvan

Keyword(s):

Electron Microscopy ◽

Radiation Damage ◽

Structural Integrity ◽

Analytical Electron Microscopy ◽

High Dose ◽

Dose Rates ◽

Special Cases ◽

Analytical Electron ◽

Atom Migration ◽

Beam Damage

Over the past five years it has become evident that radiation damage provides the fundamental limit to the study of blomolecular structure by electron microscopy. In some special cases structural determinations at very low doses can be achieved through superposition techniques to study periodic (Unwin & Henderson, 1975) and nonperiodic (Saxton & Frank, 1977) specimens. In addition, protection methods such as glucose embedding (Unwin & Henderson, 1975) and maintenance of specimen hydration at low temperatures (Taylor & Glaeser, 1976) have also shown promise. Despite these successes, the basic nature of radiation damage in the electron microscope is far from clear. In general we cannot predict exactly how different structures will behave during electron Irradiation at high dose rates. Moreover, with the rapid rise of analytical electron microscopy over the last few years, nvicroscopists are becoming concerned with questions of compositional as well as structural integrity. It is important to measure changes in elemental composition arising from atom migration in or loss from the specimen as a result of electron bombardment.

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Electron-diffraction studies in synthetic polymer materials

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100075579 ◽

1983 ◽

Vol 41 ◽

pp. 362-365

Author(s):

D.T. Grubb

Keyword(s):

Electron Diffraction ◽

Synthetic Polymer ◽

Polymer Materials ◽

Crystallographic Structure ◽

High Dose ◽

Electron Dose ◽

Dose Rates ◽

First Case ◽

Diffraction Patterns ◽

The Many

Diffraction studies in polymeric and other beam sensitive materials may bring to mind the many experiments where diffracted intensity has been used as a measure of the electron dose required to destroy fine structure in the TEM. But this paper is concerned with a range of cases where the diffraction pattern itself contains the important information.In the first case, electron diffraction from paraffins, degraded polyethylene and polyethylene single crystals, all the samples are highly ordered, and their crystallographic structure is well known. The diffraction patterns fade on irradiation and may also change considerably in a-spacing, increasing the unit cell volume on irradiation. The effect is large and continuous far C94H190 paraffin and for PE, while for shorter chains to C 28H58 the change is less, levelling off at high dose, Fig.l. It is also found that the change in a-spacing increases at higher dose rates and at higher irradiation temperatures.

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Microprobe analysis of inclusion bodies related to two benzofuran derivatives

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100127785 ◽

1987 ◽

Vol 45 ◽

pp. 672-673

Author(s):

T. L. Benning ◽

P. Ingram ◽

J. D. Shelburne

Keyword(s):

Inclusion Bodies ◽

Uranyl Acetate ◽

Multiple Organ ◽

High Dose ◽

En Bloc ◽

Tissue Samples ◽

Transmission Electron ◽

Organ Systems ◽

Dense Inclusion ◽

Melanin Complex

Two benzofuran derivatives, chlorpromazine and amiodarone, are known to produce inclusion bodies in human tissues. Prolonged high dose chlorpromazine therapy causes hyperpigmentation of the skin with electron-dense inclusion bodies present in dermal histiocytes and endothelial cells ultrastructurally. The nature of the deposits is not known although a drug-melanin complex has been hypothesized. Amiodarone may also cause cutaneous hyperpigmentation and lamellar lysosomal inclusion bodies have been demonstrated within the cells of multiple organ systems. These lamellar bodies are believed to be the product of an amiodarone-induced phospholipid storage disorder. We performed transmission electron microscopy (TEM) and energy dispersive x-ray microanalysis (EDXA) on tissue samples from patients treated with these drugs, attempting to detect the sulfur atom of chlorpromazine and the iodine atom of amiodarone within their respective inclusion bodies.A skin biopsy from a patient with hyperpigmentation due to prolonged chlorpromazine therapy was fixed in 4% glutaraldehyde and processed without osmium tetroxide or en bloc uranyl acetate for Epon embedding.

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Acetaminophen: Neonatal hepatotoxicity due to late pregnancy exposure

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100127906 ◽

1987 ◽

Vol 45 ◽

pp. 718-719

Author(s):

G.A. Miranda ◽

M.A. Arroyo ◽

C.A. Lucio ◽

M. Mongeotti ◽

S.S. Poolsawat

Keyword(s):

Low Dose ◽

Fetal Liver ◽

Late Pregnancy ◽

Toxic Chemicals ◽

Control Group ◽

High Dose ◽

Over The Counter ◽

Liver And Kidney ◽

Neonatal Liver ◽

Childbearing Women

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.

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Analysis of Silicon-On-Insulator Structures Formed By Oxygen Ion Implantation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100118370 ◽

1985 ◽

Vol 43 ◽

pp. 300-301

Author(s):

N. Lewis ◽

E. L. Hall ◽

A. Mogro-Campero ◽

R. P. Love

Keyword(s):

Ion Implantation ◽

Single Crystal ◽

Single Crystal Silicon ◽

Silicon Layer ◽

Device Fabrication ◽

Silicon On Insulator ◽

High Dose ◽

Crystal Silicon ◽

Oxygen Ion ◽

Oxygen Ion Implantation

The formation of buried oxide structures in single crystal silicon by high-dose oxygen ion implantation has received considerable attention recently for applications in advanced electronic device fabrication. This process is performed in a vacuum, and under the proper implantation conditions results in a silicon-on-insulator (SOI) structure with a top single crystal silicon layer on an amorphous silicon dioxide layer. The top Si layer has the same orientation as the silicon substrate. The quality of the outermost portion of the Si top layer is important in device fabrication since it either can be used directly to build devices, or epitaxial Si may be grown on this layer. Therefore, careful characterization of the results of the ion implantation process is essential.

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Evaluation of hippocampus in rhesus monkeys after chronic (1-year) inhalation exposure to marijuana: I. Electron microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100159539 ◽

1990 ◽

Vol 48 (3) ◽

pp. 398-399

Author(s):

A.M. Andrews ◽

S.W. Wilson ◽

A.C. Scallet ◽

S.F. Ali ◽

J. Bailey ◽

...

Keyword(s):

Synaptic Vesicles ◽

Rhesus Monkeys ◽

Low Dose ◽

Inhalation Exposure ◽

Synaptic Cleft ◽

High Dose ◽

Withdrawal Time ◽

Treatment Groups ◽

Ultrastructural Evidence ◽

Male Rhesus

Exposure of rhesus monkeys (Macaca mulatta) to marijuana via inhalation or to intravenous delta-9-tetrahydrocannabinol (THC), reportedly caused ultrastructural evidence of increased synaptic width. Chronic marijuana smoke in a single rhesus monkey examined after a six month withdrawal time caused ultrastructure changes in the septal, hippocampal and amygdala regions; the synaptic cleft was widened, electron opaque material was found in the cleft and in the pre- and postsynaptic regions, with some clumping of the synaptic vesicles. The objective of our study was to assess neuropathological alterations produced by chronic inhalation of marijuana smoke.Nineteen male rhesus monkeys, 3-5 years of age and weighing 3-8 kg, were divided into four treatment groups: a) sham control, b) placebo smoke (7 days/ week) c) low dose marijuana (2 times/week with 5 days/week sham) and d) high dose marijuana (7 times/week). A smoke exposure consisted of smoke from one cigarette (2.6% THC) burned down to 10 mm butt length. Smoke was administered via smoke generator (ADL II, Arthur D. Little, Inc. Cambridge, MA) and nose-mouth only masks (local production) equipped with one-way valves.

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Defect reduction in oxygen implanted silicon-on-insulator material during high-temperature annealing

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100154998 ◽

1989 ◽

Vol 47 ◽

pp. 604-605

Author(s):

P. Roitman ◽

B. Cordts ◽

S. Visitserngtrakul ◽

S.J. Krause

Keyword(s):

High Temperature ◽

Annealing Temperature ◽

Silicon On Insulator ◽

High Dose ◽

High Temperature Annealing ◽

High Current ◽

Defect Reduction ◽

Annealing Step ◽

Multiple Cycle ◽

Defect Densities

Synthesis of a thin, buried dielectric layer to form a silicon-on-insulator (SOI) material by high dose oxygen implantation (SIMOX – Separation by IMplanted Oxygen) is becoming an important technology due to the advent of high current (200 mA) oxygen implanters. Recently, reductions in defect densities from 109 cm−2 down to 107 cm−2 or less have been reported. They were achieved with a final high temperature annealing step (1300°C – 1400°C) in conjunction with: a) high temperature implantation or; b) channeling implantation or; c) multiple cycle implantation. However, the processes and conditions for reduction and elimination of precipitates and defects during high temperature annealing are not well understood. In this work we have studied the effect of annealing temperature on defect and precipitate reduction for SIMOX samples which were processed first with high temperature, high current implantation followed by high temperature annealing.

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