- not easy; requiring great physical or mental effort to accomplish or comprehend or endure; "a difficult task"; "nesting places on the cliffs are difficult of access"; "difficult times"; "why is it so hard for you to keep a secret?" (同)hard
- cause mental pain to; "The news of her childs illness distressed the mother"
- a state of adversity (danger or affliction or need); "a ship in distress"; "she was the classic maiden in distress"
- extreme physical pain; "the patient appeared to be in distress"
- the seizure and holding of property as security for payment of a debt or satisfaction of a claim; "Originally distress was a landlords remedy against a tenant for unpaid rents or property damage but now the landlord is given a landlords lien" (同)distraint
- psychological suffering; "the death of his wife caused him great distress" (同)hurt, suffering
- with pain or distress or bitterness; "he took the rejection very hard"
- (of light) transmitted directly from a pointed light source (同)concentrated
- with firmness; "held hard to the railing" (同)firmly
- very strong or vigorous; "strong winds"; "a hard left to the chin"; "a knockout punch"; "a severe blow" (同)knockout, severe
- causing great damage or hardship; "industries hit hard by the depression"; "she was severely affected by the banks failure" (同)severely
- being distilled rather than fermented; having a high alcoholic content; "hard liquor" (同)strong
- unfortunate or hard to bear; "had hard luck"; "a tough break" (同)tough
- (of speech sounds); produced with the back of the tongue raised toward or touching the velum; "Russian distinguished between hard consonants and palatalized or soft consonants"
- dispassionate; "took a hard look"; "a hard bargainer";
- dried out; "hard dry rolls left over from the day before"
- earnestly or intently; "thought hard about it"; "stared hard at the accused"
- into a solid condition; "concrete that sets hard within a few hours"
- resisting weight or pressure
- slowly and with difficulty; "prejudices die hard"
- to the full extent possible; all the way; "hard alee"; "the ship went hard astern"; "swung the wheel hard left"
- very near or close in space or time; "it stands hard by the railroad tracks"; "they were hard on his heels"; "a strike followed hard upon the plants opening"
- with effort or force or vigor; "the team played hard"; "worked hard all day"; "pressed hard on the lever"; "hit the ball hard"; "slammed the door hard"
- to cause inconvenience or discomfort to; "Sorry to trouble you, but..." (同)put_out, inconvenience, disoblige, discommode, incommode, bother
- cause bodily suffering to and make sick or indisposed (同)ail, pain
- an unwanted pregnancy; "he got several girls in trouble"
- an effort that is inconvenient; "I went to a lot of trouble"; "he won without any trouble"; "had difficulty walking"; "finished the test only with great difficulty" (同)difficulty
- a source of difficulty; "one trouble after another delayed the job"; "whats the problem?" (同)problem
- an event causing distress or pain; "what is the trouble?"; "heart trouble"
- difficult to accomplish; demanding considerable mental effort and skill; "the arduous work of preparing a dictionary"
- characterized by effort to the point of exhaustion; especially physical effort; "worked their arduous way up the mining valley"; "a grueling campaign"; "hard labor"; "heavy work"; "heavy going"; "spent many laborious hours on the project"; "set a punishing pace" (同)backbreaking, grueling, gruelling, hard, heavy, laborious, operose, punishing, toilsome
- taxing to the utmost; testing powers of endurance; "his final, straining burst of speed"; "a strenuous task"; "your willingness after these six arduous days to remain here"- F.D.Roosevelt (同)straining, strenuous
- not tractable; difficult to manage or mold; "an intractable disposition"; "intractable pain"; "the most intractable issue of our era"; "intractable metal"
- marked by stubborn resistance to authority; "the University suspended the most recalcitrant demonstrators"
- a condition or state of affairs almost beyond ones ability to deal with and requiring great effort to bear or overcome; "grappling with financial difficulties"
- the quality of being difficult; "they agreed about the difficulty of the climb" (同)difficultness
- a factor causing trouble in achieving a positive result or tending to produce a negative result; "serious difficulties were encountered in obtaining a pure reagent"
- (物事が)『難しい』,困難な,骨の折れる / (人が)『気難しい』,つきあいにくい,扱いにくい
- 〈U〉(肉体的・精神的な)『激しい苦しみ』,苦痛,苦悩,非嘆 / 《a~》(…にとっての)悩みの種《+『to』+『名』》 / 〈U〉『貧苦』,窮乏 / 〈U〉『危険状態』,難儀 / (精神的・肉体的に)〈人〉‘を'『苦しめる』,苦悩させる
- (物体が)『堅い』,(手触りが)堅固な,しっかりした / 『難しい』,努力を要する / 《名詞の前にのみ用いて》(人が)『精力的な』,勤勉な / 激しい,猛烈な / (生活などが)耐え難い,つらい / (季節・天候などが)厳しい;(雨・風などが)激しい / (人が)厳格な;(行為などが)容赦しない,無情な / (方針・条件などが)妥協(譲歩)しない,厳しい / (感情が)うらみを含む,憤然とした / (体が)筋肉質の,がんじょうな / (紙幣に対して)硬貨の,(小切手などに対して)現金の;(貨幣が)容易に兌換(だかん)できる / (子音が)硬音の(c,gがcome, goのように[k],[g]と発音される) / アルコール分の多い / (水が)硬質の / (エックス線が)透過能力が大きい / 一生懸命に,『熱心に』 / 『強く』,激しく,大いに / やっと,かろうじて / 『堅く』 / ひどく悲んで / 接近して
- 〈U〉『苦難』,心配,悩み / 〈C〉『苦労の種』,心配事,悩みの種 / 〈U〉危険[な状態],困難 / 〈U〉『骨折り』,手数,めんどう,迷惑 / 〈C〉〈U〉(政治的・社会的)紛争,騒動 / 〈U〉(機械などの)故障 / 〈C〉〈U〉病気 / 〈事が〉〈人・自分〉‘を'『悩ます』,心配させる,苦しめる / 《物事を頼むときていねいに》〈人〉‘を'『わずらわす』,じゃまする / 〈水・空気など〉‘を'かき乱す / 《おもに疑問文・否定文で》心配する,気を遣う;骨を折る
- 骨の折れる,困難な / (山などが)登りにくい,けわしくて骨の折れる / (努力などが)しんぼう強い,奮闘する(strenuous)
- (人・人の性質が)手に負えない,強情な / (物事が)処理しにくい,取り扱いにくい
- かたくなで手に負えない,言うことを聞かない / 扱いにくい人
- 〈U〉『難しさ』,困難 / 〈C〉『困難なこと』,難事,障害 / 〈C〉《通例複数形で》『困難な状況』,(特に)財政困難 / 〈C〉〈U〉(…との)不和,仲たがい《+『with』(『between』)+『名』》 / 〈C〉苦情,反対
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- Acrodermatitis continua of Hallopeau (ACH): Two cases successfully treated with adalimumab.
- Di Costanzo L, Napolitano M, Patruno C, Cantelli M, Balato N.Author information Department of Clinical Medicine and Surgery, University of Naples Federico II , Naples , Italy.AbstractAbstract Acrodermatitis continua of Hallopeau (ACH), also known as dermatitis repens or acrodermatitis perstans, is a rare acropustular eruption, characterized by sterile pustules, paronychia and atrophic skin changes, onychodystrophy and osteolysis of the distal phalanges of the fingers and toes. While some consider ACH a distinct entity, many believe it to be a variant of pustular psoriasis, especially as cases of ACH progressing to generalized pustular psoriasis. The treatment options used are various; however, its typical cyclic recurrences, which induce important physical and psychological morbidity, may render this pathology difficult to treat. Hence, it was considered important to review the evolution of treatment options available thus far including use of biologics. Hereby, we report two patients with ACH who were successfully treated with adalimumab. By analogy to the efficacy of TNF-α antagonists in the treatment of generalized pustular psoriasis, the two patients we report illustrate the long-term efficacy and safety of adalimumab in the treatment of Hallopeau's acrodermatitis refractory to therapies.
- The Journal of dermatological treatment.J Dermatolog Treat.2014 Dec;25(6):489-94. doi: 10.3109/09546634.2013.848259. Epub 2013 Nov 12.
- Abstract Acrodermatitis continua of Hallopeau (ACH), also known as dermatitis repens or acrodermatitis perstans, is a rare acropustular eruption, characterized by sterile pustules, paronychia and atrophic skin changes, onychodystrophy and osteolysis of the distal phalanges of the fingers and toes. W
- PMID 24215490
- Three cases of perioral dermatitis related to fusobacteria treated with β-lactam antibiotics.
- Ishiguro N, Maeda A, Suzuki K, Yamana Y, Fukuya Y, Kawashima M.Author information Department of Dermatology, Tokyo Women's Medical University , Tokyo , Japan.AbstractBackground: The oral tetracyclines, especially minocycline hydrochloride, are often used as an effective treatment for perioral dermatitis; however, they are sometimes difficult to use, especially in children, because of the side effects. Objective:The effectiveness of β-lactam antibiotics was evaluated in three cases of perioral dermatitis. Methods: Three Japanese patients with perioral dermatitis were treated with cefcapene pivoxil hydrochloride hydrate per os 100-300 mg/day. They were one girl (aged 10 years) and two adult women (aged 32 and 37 years respectively). One of the adult patients had a past history of Meniere's disease and the other had had a side effect, vertigo, from minocycline hydrochloride treatment. The presence of fusobacteria before and after the treatment was examined using the tape-stripping toluidine blue method. Results:These patients showed the improvement in 1-2 weeks and were much improved or cured after 2-5 weeks. No side effects were found during the treatment. Fusobacteria were positive before treatment but became negative after the treatment in all of them. Conclusion: The β-lactam antibiotics might be a useful treatment for perioral dermatitis, especially in cases who cannot take tetracyclines.
- The Journal of dermatological treatment.J Dermatolog Treat.2014 Dec;25(6):507-9. doi: 10.3109/09546634.2012.757284. Epub 2013 Feb 24.
- Background: The oral tetracyclines, especially minocycline hydrochloride, are often used as an effective treatment for perioral dermatitis; however, they are sometimes difficult to use, especially in children, because of the side effects. Objective:The effectiveness of β-lactam antibiotics was eval
- PMID 23240905
- Curcumin amorphous solid dispersions: the influence of intra and intermolecular bonding on physical stability.
- Wegiel LA, Zhao Y, Mauer LJ, Edgar KJ, Taylor LS.Author information Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University , West Lafayette, IN , USA .AbstractWe have investigated the physical stability of amorphous curcumin dispersions and the role of curcumin-polymer intermolecular interactions in delaying crystallization. Curcumin is an interesting model compound as it forms both intra and intermolecular hydrogen bonds in the crystal. A structurally diverse set of amorphous dispersion polymers was investigated; poly(vinylpyrrolidone), Eudragit E100, carboxymethyl cellulose acetate butyrate, hydroxypropyl methyl cellulose (HPMC) and HPMC-acetate succinate. Mid-infrared spectroscopy was used to determine and quantify the extent of curcumin-polymer interactions. Physical stability under different environmental conditions was monitored by powder X-ray diffraction. Curcumin chemical stability was monitored by UV-Vis spectroscopy. Isolation of stable amorphous curcumin was difficult in the absence of polymers. Polymers proved to be effective curcumin crystallization inhibitors enabling the production of amorphous solid dispersions; however, the polymers showed very different abilities to inhibit crystallization during long-term storage. Curcumin intramolecular hydrogen bonding reduced the extent of its hydrogen bonding with polymers; hence most polymers were not highly effective crystallization inhibitors. Overall, polymers proved to be crystallization inhibitors, but inhibition was limited due to the intramolecular hydrogen bonding in curcumin, which leads to a decrease in the ability of the polymers to interact at a molecular level.
- Pharmaceutical development and technology.Pharm Dev Technol.2014 Dec;19(8):976-86. doi: 10.3109/10837450.2013.846374. Epub 2013 Nov 6.
- We have investigated the physical stability of amorphous curcumin dispersions and the role of curcumin-polymer intermolecular interactions in delaying crystallization. Curcumin is an interesting model compound as it forms both intra and intermolecular hydrogen bonds in the crystal. A structurally di
- PMID 24192454
- Systematic analysis of silver nanoparticle ionic dissolution by tangential flow filtration: toxicological implications.
- Maurer EI, Sharma M, Schlager JJ, Hussain SM.Author information 711 Human Performance Wing/RHDJ, Human Effectiveness Directorate, Air Force Research Laboratory, Wright-Patterson Air Force Base , Dayton, Ohio , USA.AbstractIn the field of toxicology of nanomaterials, scientists have not clearly determined if the observed toxicological events are due to the nanoparticles (NPs) themselves or the dissolution of ions released into the biophysiological environment or both phenomenon participate in combination based upon their bioregional and temporal occurrence during exposure conditions. Consequently, research involving the toxicological analysis of silver NPs (Ag-NPs) has shifted towards assessment of 'nanosized' silver in comparison to its solvated 'ionic' counterpart. Current literature suggests that dissolution of ions from Ag-NPs may play a key role in toxicity; however, the present assessment methodology to separate ions from NPs still requires improvement before a definitive cause of toxicity can be determined. Recently, centrifugation-based techniques have been employed to obtain solvated ions from the NP solution, but this approach leads to NP agglomeration, making further toxicological analysis difficult to assess. Additionally, extremely small NPs are retained in the supernatant even after ultracentrifugation, leading to incomplete separation of ions from their respective NPs. To address these complex toxicology issues we applied enhanced separation techniques with the aim to study levels of ions originating from the Ag-NP using separation by a recirculating tangential flow filtration system. This system uses a unique diffusion-driven filtration method that retains large particles within the continuous flow path, while allowing the solution (ions) to pass through molecular filters by lateral diffusion separation. Use of this technique provides reproducible NP separation from their solvated ions which permits for further quantification using an inductively coupled plasma mass spectrometry or comparison use in bioassay exposures to biological systems. In this study, we thoroughly characterised NPs in biologically relevant solutions to understand the dissolution of Ag-NPs (10 and 50 nm) over time. Our results suggest that the ion dissolution from Ag-NPs is dependent on parameters such as exposure time, chemical composition and temperature of the exposure solution. Further, the well-characterised separated ionic and NP solutions were exposed to a lung epithelial cell line (A549) to evaluate the toxicity of each fraction. Results suggest that although Ag-NPs (unseparated) show concentration-dependent toxicity, dissolution of ions appears to exacerbate the toxicological effect. This finding adds data to the set of probable toxic exposure mechanisms elicited by metallic nanomaterials and provides important consideration when assessing findings of key cell function modulation.
- Nanotoxicology.Nanotoxicology.2014 Nov;8(7):718-27. doi: 10.3109/17435390.2013.824127. Epub 2013 Aug 1.
- In the field of toxicology of nanomaterials, scientists have not clearly determined if the observed toxicological events are due to the nanoparticles (NPs) themselves or the dissolution of ions released into the biophysiological environment or both phenomenon participate in combination based upon th
- PMID 23848466
- 臨床報告 診断に苦慮した膀胱癌術後再発による直腸輪状狭窄の1例
- 症例報告 術前には卵巣成熟囊胞性奇形腫を診断できなかった抗NMDA受容体脳炎の1例
- 困難事例に対するACTによるアウトリーチ支援の現在 (特集 精神科領域におけるアウトリーチ支援の現在)
- difficult 【形】 〔達成が〕困難な、厳しい【文例】 〔耐えるのが〕苦しい、つ... - アルクがお届けする進化するオンライン英和・和英辞書データベース。一般的な単語や連語から、イディオム、専門用語、スラングまで幅広く収録。
- It might be difficult-- and it was so -- to conceive how he should exist hereafter, so earthly and sensuous did he seem; but surely his existence here, admitting that it was to terminate with his last breath, had been not unkindly given ...
- Difficult definition, not easily or readily done; requiring much labor, skill, or planning to be performed successfully; hard: a difficult job. See more. Dictionary.com Word of the Day Translate Games Blog Thesaurus.com Apps Log In ...
- plasmapheresis has been utilized rarely in patients with severe intractable pruritus.
- Ongoing diuretic resistance with intractable edema and hypertension in advanced CKD may serve as an indication to initiate dialysis.(HIM.1764)
- difficulty in walking
- walking difficulty