Efficacy of Low-Dose versus High-Dose Continuous Cyclic Azithromycin Therapy for Preventing Acute Exacerbations of COPD

Respiration ◽  
2021 ◽  
pp. 1-8
Author(s):  
Xavier Pomares ◽  
Concepción Montón ◽  
Daniel Huertas ◽  
Alicia Marín ◽  
Ester Cuevas ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Therapy Group ◽  
High Dose ◽  
University Hospitals ◽  
Copd Exacerbations ◽  
Before And After ◽  
Dosing Regimens ◽  
Maximal Medical Therapy ◽  
Severe Copd

<b><i>Background:</i></b> Long-term azithromycin therapy significantly reduces the frequency of COPD exacerbations (ECOPD). However, previous studies have used different dosing regimens, and the efficacy of these regimens has not been compared. <b><i>Objective:</i></b> Compare the efficacy of low-dose with high-dose continuous cyclic azithromycin (CC-A) in severe COPD. <b><i>Methods:</i></b> Patients with severe COPD and repeated exacerbations (ECOPD ≥4 or ≥3 with at least 1 hospital admission in the previous year) were prospectively recruited (January 2017 to December 2019) as a multicenter cohort (from 3 university hospitals in the Barcelona area) and treated with low-dose CC-A: 250 mg 3 times per week (250-CC-A group). This cohort was compared with a historical (January 2007 to December 2013) single-center cohort of severe COPD with frequent ECOPD treated with high-dose CC-A: 500 mg 3 times per week (500-CC-A group). To assess differences in ECOPD prevention according to the administration of low-dose or high-dose CC-A, moderate-to-severe ECOPD was evaluated during the 12-month period before and after starting CC-A therapy. <b><i>Results:</i></b> Fifty-eight patients with severe COPD were evaluated: 37 in the low-dose group and 21 in the high-dose group. The 250-CC-A therapy group achieved a mean reduction in moderate-to-severe ECOPD of 65.6% at 12 months after starting CC-A therapy (with a 61.5% reduction in hospitalizations), while the 500-CC-A group achieved a reduction of 60.5% (with a 44.8% reduction in hospitalizations). No significant differences between 250-CC-A and 500-CC-A dosages were observed in the mean annual reduction of moderate-to-severe ECOPD (<i>p</i> = 0.55) or hospitalizations (<i>p</i> = 0.07) with respect to the year prior to starting CC-A. <b><i>Conclusions:</i></b> Low-dose 250-CC-A therapy over a 1-year period is similar to high-dose 500-CC-A in reducing exacerbation frequency in severe COPD patients with frequent ECOPD despite maximal medical therapy.

scholarly journals Effectiveness and Toxicity of Methotrexate in Juvenile Idiopathic Arthritis: Comparison of 2 Initial Dosing Regimens

2010 ◽  
Vol 37 (4) ◽  
pp. 870-875 ◽  
Author(s):  
MARA L. BECKER ◽  
CARLOS D. ROSÉ ◽  
RANDY Q. CRON ◽  
DAVID D. SHERRY ◽  
WARREN B. BILKER ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Clinical Response ◽  
Dose Group ◽  
Low Dose ◽  
Liver Toxicity ◽  
High Dose Group ◽  
High Dose ◽  
Active Joint ◽  
Significant Difference ◽  
Dosing Regimens

Objective.To compare the incidence of liver toxicity and clinical response between 2 initial dosing regimens of methotrexate (MTX) for treatment of juvenile idiopathic arthritis (JIA).Methods.Clinical and laboratory data were abstracted from the medical records of 220 children newly prescribed MTX from the same geographic region. One cohort received initial doses of MTX > 0.5 mg/kg/week (“high-dose”) and one cohort received initial doses of MTX ≤ 0.5 mg/kg/week (“low-dose”). Toxicity was defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) above the normal range, and positive clinical response was defined as a reduction in active joint count during the first 6 months of MTX therapy.Results.One hundred twenty-six children were in the high-dose MTX group, 94 in the low-dose MTX group. At 6 months, the high-dose group was more likely to have an elevated AST or ALT (adjusted OR 3.89, 95% CI 1.82–8.29, p < 0.0001). Subjects receiving both MTX and nonsteroidal antiinflammatory drugs (NSAID) had no significant difference between groups in change of active joint count, while subjects in the high-dose group but not taking NSAID had more active joints (p = 0.036) at 6 months compared to the low-dose group.Conclusion.Initial high-dose MTX was associated with an increased risk of at least one liver enzyme abnormality with no significant improvement in active joint count. This suggests that there is no apparent benefit, while the potential for liver toxicity is increased, when using higher doses of MTX at treatment inception in patients with JIA.

Benefit/Risk Profile of Combined Antiplatelet Therapy with Ticlopidine and Aspirin

1991 ◽  
Vol 65 (05) ◽  
pp. 504-510 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
Walter Bernini ◽  
Guido Lazzerini ◽  
Giuliana Buti Strata ◽  
...  
Keyword(s):  
Platelet Function ◽  
Low Dose ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Stable Coronary Artery Disease ◽  
High Dose ◽  
Single Drug ◽  
Before And After ◽  
Serum Thromboxane ◽  
Artery Disease

SummaryTiclopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 μM; adrenaline 0.75-2.5 μM; collagen 1.5-150 μg/ml; arachidonic acid 1 mM; PAF 1 μM; adrenaline 0.17 μM + ADP 0.62 μM; serum thromboxane ([TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p <0.05) than either treatment alone in depressing responses to high-dose collagen (% over control, mean ± SEM: T: 95 ± 3; ASA: 96 ± 5; T + ASA: 89 ± 4). Serum TXB2 (basal, ng/ml: 380 ± 54) did not change with T (372 ± 36), dropped to <1 ng/ml on ASA injection and slightly re-increased to 9.1 ± 3.1 ng/ml on oral low-dose ASA. BT (basal 7.4 ± 0.6 min) was affected similarly by T (9.2 ± 0.8) or ASA (9.7 ± 0.9) alone, but increased to 15.0 ± 0.7 min on combination treatment (106% increase over control). Thus, the strong synergism in BT prolongation by ASA-T combination has a counterpart in the inhibition of platelet function in response to strong stimuli such as high-dose collagen, not otherwise affected significantly by single-drug treatment. This effect is a possible rationale for the clinical evaluation of T + ASA combination.

Intensive Initial Oral Anticoagulation and Shorter Heparin Treatment in Deep Vein Thrombosis

1984 ◽  
Vol 52 (03) ◽  
pp. 276-280 ◽  
Author(s):  
Sam Schulman ◽  
Dieter Lockner ◽  
Kurt Bergström ◽  
Margareta Blombäck
Keyword(s):  
Deep Vein Thrombosis ◽  
Oral Anticoagulation ◽  
Dose Group ◽  
Low Dose ◽  
Clinical Signs ◽  
Coagulation Factor ◽  
High Dose ◽  
Vein Thrombosis ◽  
Heparin Treatment ◽  
Deep Vein

SummaryIn order to investigate whether a more intensive initial oral anticoagulation still would be safe and effective, we performed a prospective randomized study in patients with deep vein thrombosis. They received either the conventional regimen of oral anticoagulation (“low-dose”) and heparin or a more intense oral anticoagulation (“high-dose”) with a shorter period of heparin treatment.In the first part of the study 129 patients were randomized. The “low-dose” group reached a stable therapeutic prothrombin complex (PT)-level after 4.3 and the “high-dose” group after 3.3 days. Heparin was discontinued after 6.0 and 5.0 days respectively. There was no difference in significant hemorrhage between the groups, and no clinical signs of progression of the thrombosis.In the second part of the study another 40 patients were randomized, followed with coagulation factor II, VII, IX and X and with repeated venograms. A stable therapeutic PT-level was achieved after 4.4 (“low-dose”) and 3.7 (“high-dose”) days, and heparin was discontinued after 5.4 and 4.4 days respectively. There were no clinical hemorrhages, the activity of the coagulation factors had dropped to the same level in both groups at the time when heparin was discontinued and no thromboembolic complications occurred.Our oral anticoagulation regimen with heparin treatment for an average of 4.4-5 days seems safe and reduces in-patient costs.

scholarly journals Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Leukocyte Adhesion ◽  
Endothelial Glycocalyx ◽  
High Dose Group ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

High-dose statin therapy and the risk of haemorrhagic stroke in Asian patients with stable coronary artery disease: insights from the REAL-CAD study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Takahashi ◽  
K Tsuchida ◽  
Y Sato ◽  
S Iimuro ◽  
K Kario ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Dose Group ◽  
Low Dose ◽  
Japanese Patients ◽  
Haemorrhagic Stroke ◽  
High Dose ◽  
The Real ◽  
Artery Disease ◽  
Stable Cad ◽  
Bleeding Score

Abstract Background/Introduction The REAL-CAD study identified that aggressive lipid lowering with high-dose statin reduced cardiovascular events also in Japanese patients with coronary artery disease (CAD). However, data from the SPARCL trial found that the benefits of high-dose atorvastatin treatment were partially offset by an increase in haemorrhagic stroke (HS). Although meta-analysis showed statin does not increase HS in Western countries, the evidence about the relation between statin and HS in Asian countries is still conflicting. In addition, the CREDO-Kyoto score is one of the prediction scorings for bleeding after coronary revascularization and might be a useful tool for the prediction of HS in this cohort. Recognizing the risk of HS and predicting of HS in the Asian cohort is clinically important. Purpose This study examined the factors associated with HS using the REAL-CAD cohort. Furthermore, we evaluated the performance of the CREDO-Kyoto bleeding risk score to predict HS in this cohort. We also performed the corresponding analysis of ischaemic stroke for reference purposes. Methods We sub-analysed the REAL-CAD study, prospective, multicentre, randomized, open-label, blinded endpoint study, in which 13,054 Japanese patients with stable CAD were randomized to high-dose (4 mg/day) or low-dose (1 mg/day) pitavastatin. Associations for stroke were determined using competing risk models: the Fine and Gray subdistribution hazards model accounting for the competing risk of death in models of haemorrhagic and ischaemic stroke in REAL-CAD trial. Patients were categorized to low (score 0), moderate (score 1–2), and high (score&gt;3) according to CREDO-Kyoto bleeding score for predicting of HS. Results The HS events in high-dose group tended to be higher than low-dose group (4mg vs. 1mg: 43 (0.7%) vs. 30 (0.5%)). The associated factors of HS on univariate analysis were non-prior myocardial (hazard ratio (HR): 0.62, 95% CI: 0.39–0.99) and non-prior cerebral (HR: 0.25, 95% CI: 0.09–0.70) infarction, atrial fibrillation (HR: 2.4, 95% CI: 1.2–4.7), prior HS (HR: 4.2, 95% CI: 1.5–11.8), anaemia (HR: 2.4, 95% CI: 1.4–4.1), and non-statins use before run-in period (HR: 0.52, 95% CI: 0.28–0.99). High-dose pitavastatin was not a correlate with HS. The multivariate analysis revealed anaemia might have a relation with HS (HR: 4.3, 95% CI: 0.90–20.6). The number of HS was the highest in the high CREDO-Kyoto bleeding score group (Figure 1, HR: 2.4, 95% CI: 1.3–4.6), whereas there was no significant difference in the number of HS between the moderate- and low-risk groups (HR: 1.4, 95% CI: 0.84–2.3). Conclusions High-dose pitavastatin was not associated with the incidence of HS in this large Japanese cohort with stable CAD. High CREDO-Kyoto bleeding score was associated with HS as compared with low or moderate scores, even each of the variables consisting of CREDO-Kyoto score was not associated with HS. Figure 1 Funding Acknowledgement Type of funding source: None

scholarly journals Spatio-temporal biodistribution of 89Zr-oxine labeled huLym-1-A-BB3z-CAR T-cells by PET imaging in a preclinical tumor model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naomi S. Sta Maria ◽  
Leslie A. Khawli ◽  
Vyshnavi Pachipulusu ◽  
Sharon W. Lin ◽  
Long Zheng ◽  
...  
Keyword(s):  
T Cells ◽  
Real Time ◽  
Pet Imaging ◽  
Dose Group ◽  
Low Dose ◽  
High Dose ◽  
Car T Cells ◽  
Nsg Mice ◽  
Car T

AbstractQuantitative in vivo monitoring of cell biodistribution offers assessment of treatment efficacy in real-time and can provide guidance for further optimization of chimeric antigen receptor (CAR) modified cell therapy. We evaluated the utility of a non-invasive, serial 89Zr-oxine PET imaging to assess optimal dosing for huLym-1-A-BB3z-CAR T-cell directed to Lym-1-positive Raji lymphoma xenograft in NOD Scid-IL2Rgammanull (NSG) mice. In vitro experiments showed no detrimental effects in cell health and function following 89Zr-oxine labeling. In vivo experiments employed simultaneous PET/MRI of Raji-bearing NSG mice on day 0 (3 h), 1, 2, and 5 after intravenous administration of low (1.87 ± 0.04 × 106 cells), middle (7.14 ± 0.45 × 106 cells), or high (16.83 ± 0.41 × 106 cells) cell dose. Biodistribution (%ID/g) in regions of interests defined over T1-weighted MRI, such as blood, bone, brain, liver, lungs, spleen, and tumor, were analyzed from PET images. Escalating doses of CAR T-cells resulted in dose-dependent %ID/g biodistributions in all regions. Middle and High dose groups showed significantly higher tumor %ID/g compared to Low dose group on day 2. Tumor-to-blood ratios showed the enhanced extravascular tumor uptake by day 2 in the Low dose group, while the Middle dose showed significant tumor accumulation starting on day 1 up to day 5. From these data obtained over time, it is apparent that intravenously administered CAR T-cells become trapped in the lung for 3–5 h and then migrate to the liver and spleen for up to 2–3 days. This surprising biodistribution data may be responsible for the inactivation of these cells before targeting solid tumors. Ex vivo biodistributions confirmed in vivo PET-derived biodistributions. According to these studies, we conclude that in vivo serial PET imaging with 89Zr-oxine labeled CAR T-cells provides real-time monitoring of biodistributions crucial for interpreting efficacy and guiding treatment in patient care.

scholarly journals Glycerol Monocaprylate Modulates Gut Microbiota and Increases Short-Chain Fatty Acids Production without Adverse Effects on Metabolism and Inflammation

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1427
Author(s):  
Junhui Zhang ◽  
Fengqin Feng ◽  
Minjie Zhao
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Dose Group ◽  
Low Dose ◽  
Short Chain Fatty Acids ◽  
Normal Diet ◽  
Short Chain ◽  
High Dose ◽  
Dose Treatment ◽  
Chain Fatty Acids

Glycerol monocaprylate (GMC) is a glycerol derivative of medium-chain fatty acids (MCFAs) and is widely used as a preservative in food processing. However, GMC and its hydrolytic acid (octylic acid) have antibacterial properties that may affect the physiology and intestinal microecology of the human body. Therefore, in this study, the effects of two different dosages of GMC (150 and 1600 mg kg−1) on glucose, lipid metabolism, inflammation, and intestinal microecology of normal diet-fed C57BL/6 mice were comprehensively investigated. The obtained results showed that the level of triglycerides (TGs) in the low-dose group down-regulated significantly, and the anti-inflammatory cytokine interleukin 10 (IL-10) significantly increased, while the pro-inflammatory cytokines monocyte chemotactic protein 1 (MCP-1) and interleukin 1beta (IL-1β) in the high-dose group were significantly decreased. Importantly, GMC promoted the α-diversity of gut microbiota in normal-diet-fed mice, regardless of dosages. Additionally, it was found that the low-dose treatment of GMC significantly increased the abundance of Lactobacillus, while the high-dose treatment of GMC significantly increased the abundance of SCFA-producers such as Clostridiales, Lachnospiraceae, and Ruminococcus. Moreover, the content of short-chain fatty acids (SCFAs) was significantly increased by GMC supplementation. Thus, our research provides a novel insight into the effects of GMC on gut microbiota and physiological characteristics.

scholarly journals Recombinant Human Thyrotropin-Stimulated Radioiodine Therapy in Patients with Multinodular Goiters: A Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Vol 52 (12) ◽  
pp. 841-849
Author(s):  
Chunmei Xu ◽  
Ping Wang ◽  
Huikai Miao ◽  
Tianyue Xie ◽  
Xiaojun Zhou ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Dose Group ◽  
Low Dose ◽  
Radioiodine Therapy ◽  
Meta Analysis ◽  
High Dose Group ◽  
High Dose ◽  
Fixed Effects Model ◽  
Recombinant Human Thyrotropin

AbstractA potential reduction of goiter volume (GV) of recombinant human thyrotropin (rhTSH) on multinodular goiters (MNG) was previously reported but controversial. Hence we conducted a meta-analysis to estimate the effect of rhTSH-stimulated radioiodine therapy in patients with MNG. PubMed, Cochrane, CNKI, VIP, and Wanfang databases were searched. Mean difference (MD) and odds ratios with 95% confidence intervals (95% CI) were derived by using an inverse variance random-effects model and fixed-effects model, respectively. Six studies (n=237) were involved in the analysis. For 12 months follow up, high dose (>0.1 mg) of rhTSH significantly reduced GV (MD=17.61; 95% CI=12.17 to 23.04; p<0.00001) compared with placebo. No effective pooled results of low dose of rhTSH (<0.1 mg) were applicable for only one study included. For 6 months follow up, the source of heterogeneity was determined by subgroup and sensitivity analysis. High dose group showed vast improvement in GV reduction (MD=16.62; 95% CI=1.34 to 31.90; p=0.03). The reduction of low dose group compared with placebo was inferior to high dose group. No available data were obtained to assess the influence of rhTSH after 36 months follow up for the only included study. Hypothyroidism incidence was higher for rhTSH group. No publication bias was seen. High dose of rhTSH treatment-stimulated radioactive 131I therapy after 6 months and 12 months follow up had a better effect in reducing GV, but with higher incidence of hypothyroidism. Owing to the limited methodological quality, more clinical researches are warranted in the future.

scholarly journals Early Administration of Tolvaptan Can Improve Survival in Patients with Cirrhotic Ascites

2021 ◽  
Vol 10 (2) ◽  
pp. 294
Author(s):  
Atsushi Hosui ◽  
Takafumi Tanimoto ◽  
Toru Okahara ◽  
Munehiro Ashida ◽  
Kohsaku Ohnishi ◽  
...  
Keyword(s):  
Conventional Therapy ◽  
Low Dose ◽  
Therapy Group ◽  
Survival Rates ◽  
Refractory Ascites ◽  
High Dose ◽  
Term Survival ◽  
Conventional Therapy Group ◽  
One Year ◽  
The One

(1) Backgrounds and aim: Tolvaptan, a selective vasopressin type 2 receptor antagonist, was approved for ascites, and its short-term efficacy and safety have been confirmed. However, it is still unclear whether this novel drug may improve long-term survival rates in cirrhotic patients with ascites. (2) Patients and methods: A total of 206 patients who responded insufficiently to conventional diuretics and were hospitalized for refractory ascites for the first time were retrospectively enrolled in this study. Among them, the first 57 consecutive patients were treated with conventional diuretics (the conventional therapy group); the latter 149 consecutive patients were treated with tolvaptan in addition to the conventional therapy (the tolvaptan group). (3) Results: The exacerbation of renal function was significantly milder in the tolvaptan group than in the conventional therapy group. The prognostic factors for survival in the tolvaptan group were being male, having hyperbilirubinemia, having a high blood urea nitrogen (BUN), and receiving high-dose furosemide at the start of tolvaptan treatment. The one-year and three-year cumulative survival rates were 67.8 and 45.3%, respectively, in patients with low-dose furosemide (<40 mg/day) at the start of tolvaptan treatment. The prognosis was significantly better in the tolvaptan group with low-dose furosemide than in the conventional therapy group (p < 0.001). (4) Conclusion: Tolvaptan can improve survival in patients with cirrhotic ascites, especially when tolvaptan is started before high-dose furosemide administration.

A New Hafnium-Beryllium System Prioduced by Ion Implantation and Annealing Techniques

1983 ◽  
Vol 27 ◽  
Author(s):  
J.C. Soares ◽  
A.A. Melo ◽  
M.F. DA Silva ◽  
E.J. Alves ◽  
K. Freitag ◽  
...  
Keyword(s):  
Ion Implantation ◽  
Single Crystals ◽  
Room Temperature ◽  
Low Dose ◽  
Correlation Method ◽  
High Dose ◽  
Tetrahedral Sites ◽  
Time Differential ◽  
Before And After ◽  
Beryllium Foil

ABSTRACTLow and high dose hafnium imolanted beryllium samoles have been prepared at room temperature by ion implantation of beryllium commercial foils and single crystals. These samples have been studied before and after annealing with the time differential perturbed angular correlation method (TDPAC) and with Rutherford backscattering and channeling techniques. A new metastable system has been discovered in TDPAC-measurements in a low dose hafnium implanted beryllium foil annealed at 500°C. Channeling measurements show that the hafnium atoms after annealing, are in the regular tetrahedral sites but dislocated from the previous position occupied after implantation. The formation of this system is connected with the redistribution of oxygen in a thin layer under the surface. This effect does not take place precisely at the same temperature in foils and in single crystals.

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