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1.
Although ketoconazole has been used extensively in dogs for the treatment of various fungal infections, information about adverse effects is mainly anecdotal. Common adverse effects in humans include dose-dependant anorexia, nausea and vomiting, allergic rashes and pruritus. Drug-induced hepatitis is very rare, but potentially fatal. The aim of this study was to evaluate the type and frequency of adverse effects associated with ketoconazole therapy in dogs treated for skin diseases and any possible influence of dosage, duration of therapy, signalment or concurrent medication. The medical records of 632 dogs treated with ketoconazole (2.6–33.4 mg/kg) were reviewed. Adverse effects occurred in 14.6% (92 dogs) and included vomiting (7.1%), anorexia (4.9%), lethargy (1.9%), diarrhea (1.1%), pruritus (0.6%), erythema (0.3%) and other adverse effects (2.5%). Of the dogs with other adverse effects, four of 16 (25%) were ataxic and three of these received concurrent ivermectin. Adverse effects were significantly more often recorded in dogs concurrently treated with ciclosporin ( P =  0.034) or ivermectin ( P =  0.007). Increased liver enzyme levels were reported rarely, and icterus was not seen in any of the dogs. However, monitoring liver enzymes during therapy is recommended, although this might not necessarily prevent severe idiosyncratic hepatotoxicity.  相似文献   

2.
Chelated zinc–carnosine and vitamin E [GastriCalm® (GCM); Teva Animal Health] is marketed as an anti‐emetic supplement for dogs to assist the repair of damaged stomach and intestinal mucosa. The purpose of this prospective, double‐blinded, placebo‐controlled trial was to determine whether GCM reduced the frequency of vomiting, diarrhoea and appetite changes during initiation of ciclosporin (Atopica®; Novartis Animal Health) therapy for the treatment of canine atopic dermatitis. Sixty privately owned dogs diagnosed with atopic dermatitis were randomly assigned to GCM (n = 30) or placebo (n = 30) groups. All dogs received ～5 mg/kg ciclosporin (range, 3.5–5.8 mg/kg) once daily. Dogs <13.6 kg received half a tablet of GCM or placebo; dogs ≥13.6 kg received one tablet once daily. GastriCalm® or placebo was administered 30 min prior to eating, and the ciclosporin was administered 2 h after feeding. Owners recorded episodes of vomiting, diarrhoea and appetite changes. Dogs were examined on days 0 and 14. Forty‐one of 60 dogs (68.3%) had at least one episode of vomiting, diarrhoea or appetite change, leaving nine placebo dogs (30%) and ten GCM dogs (33.3%) free of adverse events (AE). Twenty‐seven of 60 dogs (45%) vomited, and 15 of 60 (25%) had diarrhoea. There was no significant difference in episodes of individual AEs, but the placebo group had a significantly lower total AE score (summation of episodes of appetite change, vomiting and diarrhoea; P = 0.022). Small dogs (<6.82 kg) had significantly fewer total AEs in both treatment groups and tolerated ciclosporin better than larger dogs (P < 0.05).  相似文献   

3.
Summary

Adverse reactions to various trimethoprim‐sulphonamide (T‐S) combinations were studied retrospectively in dogs and cats referred to the Utrecht University Department of Clinical Sciences of Companion Animals during the period 1985–1994. Dermatological and systemic reactions were observed in 19 dogs and 2 cats. Specific histological reaction patterns were seen in 3 dogs with toxic epidermal necrolysis, in 1 dog and 1 cat with erythema multiforme, and in 1 dog with pemphigus foliaceus. Diagnostic criteria used in humans proved to be reliable in dogs and cats as well. Adverse reactions were observed within 7–14 days after administration and were most often due to sulphadiazine (76%) and sulphatroxazole (14%). The incidence of adverse reactions to T‐S was 0.25%.  相似文献   

4.
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5.
Thrombocytopenia is commonly encountered in veterinary oncology. Currently, there are no standard guidelines regarding the administration of chemotherapy to the patients with thrombocytopenia. This observational epidemiological cohort study aimed to determine whether thrombocytopenic dogs were at increased risk of gastrointestinal adverse effects (vomiting, diarrhoea, inappetence) or haemorrhage following administration of standard doses of chemotherapy. The adverse effects following 77 prospectively identified episodes of thrombocytopenia (platelet count, <200 000 µL?1) were compared with the adverse effects experienced in a retrospective cohort (platelet count >200 000 µL?1), and evaluated by statistical analysis. Overall, there was no statistically significant difference in the incidence of gastrointestinal adverse effects or haemorrhage between thrombocytopenic and control dogs. The control group of dogs with lymphoma were statistically more likely to experience vomiting as an adverse effect of chemotherapy (P = 0.028). The results presented here showed no evidence for an increased risk of gastrointestinal adverse effects or haemorrhage in thrombocytopenic dogs after receiving standard doses of chemotherapy.  相似文献   

6.
In this retrospective study, a chemotherapy protocol using dexamethasone, melphalan, actinomycin D, and cytosine arabinoside (DMAC) was evaluated for efficacy and adverse event profile as a first line rescue protocol in 86 client-owned dogs previously treated with a CHOP-based protocol. Forty-three dogs (43%) achieved remission (16% complete remission, 27% partial remission), and 57% were non-responders. The median overall progression-free survival (PFS) was 24 days. Adverse events included thrombocytopenia in 41% of dogs, neutropenia in 17% of dogs, and gastrointestinal toxicity in 13% of dogs. Overall, 16% (13/79) dogs experienced grade III to IV thrombocytopenia, 8% (6/74) dogs grade III to IV neutropenia and 1% (1/79) dogs grade III to IV gastrointestinal toxicity. The efficacy of the DMAC protocol is similar to that of other rescue protocols in dogs with relapsed lymphoma but is associated with shorter PFS. The main toxicity is thrombocytopenia, which may limit treatment.  相似文献   

7.
Rectal swabs from healthy cats and dogs, and from dogs and cats with clinical diarrhoea were collected approximately every third month from May 2000 to June 2001 from six small-animal practices throughout Norway. A questionnaire was filled in for each animal. Of the 301 healthy cats sampled, 54 (18%) were positive for Campylobacter, compared to 5 out of 31 (16%) cats with diarrhoea. Campylobacter jejuni was isolated from 11 (3%), C. upsaliensis from 42 (13%) and C. coli from 2 (0.6%) of the cats sampled. Isolates from four cats (1%) could not be specified. Of the 529 healthy dogs, 124 (23%) were positive for Campylobacter, compared to 18 of 66 (27%) dogs with diarrhoea. C. jejuni was isolated from 20 (3%) and C. upsaliensis from 117 (20%) of the dogs sampled. Isolates from five dogs (0.8%) could not be specified. Eighteen out of the 20 investigated C. upsaliensis samples were resistant to streptomycin. The clinically healthy animals were included in the analysis to identify factors associated with Campylobacter prevalence. The cat model had low classification ability. The dog-data model indicated increased odds of infection with Campylobacter for dogs ≤1 year, and in dogs sampled during the spring. No difference was observed between the prevalence of Campylobacter infections in cats and dogs with diarrhoea and healthy animals.  相似文献   

8.
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9.
Background – Hypersensitivity dermatitides (HD) are frequently suspected in cats, but there are few clinical studies on safe and effective treatments in the published literature. Objectives – To establish a safe and effective dose of ciclosporin in the treatment of feline HD. Animals – One hundred client‐owned cats with feline HD. Methods – Double‐blind study, with cats randomly assigned to receive ciclosporin at either 7.0 mg/kg once daily (n = 33) or 2.5 mg/kg once daily (n = 32) or a placebo (n = 35) for 6 weeks. Results – Mean Total Lesion Scores with 7.0 mg/kg ciclosporin were significantly lower than with 2.5 mg/kg ciclosporin (P = 0.0047) or placebo (P = 0.0003) at study end. Individual Total Lesion Scores improved by >50% in 70% of the 7.0 mg/kg group, compared with 47% in the 2.5 mg/kg group and 23% in the placebo group (P = 0.0006). The investigators’ Global Assessment of Improvement was ‘excellent’ or ‘good’ in 61% of cats treated with 7.0 mg/kg ciclosporin, compared with 47% of cats given 2.5 mg/kg and 23% given placebo. The improvement in Investigator Pruritus Scores was significantly greater in cats treated with 7.0 mg/kg ciclosporin (54%) compared with both 2.5 mg/kg ciclosporin (32%; P = 0.0232) and placebo (21%; P = 0.0063). Mild gastrointestinal disorders were the most common adverse events, but these did not require cessation of therapy. Conclusions and clinical importance – Results suggest that 7.0 mg/kg ciclosporin once daily in food or per os for 6 weeks is effective and well tolerated in feline HD.  相似文献   

10.
Canine multiple myeloma (MM) is typically treated with melphalan chemotherapy. A protocol with repeated 10-day cyclical dosing of melphalan has been used at our institution but has not been described in the literature. Our objectives were to describe the outcome and adverse events of this protocol in a retrospective case series. We hypothesised the cyclical 10-day protocol would have similar outcomes compared to other reported chemotherapy protocols. Dogs diagnosed with MM that received melphalan treatment at Cornell University Hospital for Animals were identified through a database search. Records were retrospectively reviewed. Seventeen dogs met inclusion criteria. Lethargy was the most common presenting complaint. The median duration of clinical signs was 53 days (range, 2–150 days). Seventeen dogs had hyperglobulinemia with 16/17 having monoclonal gammopathies. Sixteen dogs had bone marrow aspiration and cytology performed at initial diagnosis and plasmacytosis was diagnosed in all. Based on serum globulin concentrations, 10 of 17 dogs (59%) achieved complete response (CR), and 3 dogs (18%) achieved partial response (PR), for an overall response rate of 76%. The median overall survival time was 512 days (range, 39–1065). Retinal detachment (n = 3) and maximum response of CR/PR (n = 13) were associated with overall survival on multivariate analysis (p = .045 and .046, respectively). Adverse events were minimal with diarrhoea being the most reported (n = 6). This cyclical 10-day protocol was better-tolerated with fewer adverse events than with other reported chemotherapy protocols, but response rate was also lower, likely due to a lower dosing intensity.  相似文献   

11.
Chemotherapy‐induced diarrhoea (CID) is a frequent chemotherapy adverse event in dogs. Yet, there is currently no consensus regarding its management. Smectite is a natural medical clay, widely used in the treatment of acute diarrhoea in humans. The objectives of this study were to assess the efficacy of smectite in the management of CID in dogs, and to collect epidemiological data on CID. For each episode of diarrhoea, dogs were randomized into two management groups: Smectite group, receiving smectite at 0.5 g/kg PO per day divided in two to three doses initiated at the start of CID; control group, without initial medication. In both groups, rescue metronidazole was prescribed if CID progressed or was not improved within 48 hours. Sixty dogs were recruited and received 426 chemotherapy administrations between June 2017 and March 2019. The incidence rate of CID was 110/426 (25.8%, 95% CI: 21.7%‐30.2%), and significantly differed between the chemotherapeutic drugs administered (P < .001). Metronidazole was administered in 5/54 events (9.3%, 95% CI: 3.1%‐20.3%) in the smectite group and in 40/56 events (71.4%, 95% CI: 57.5%‐82.3%) in the control group (P < .001). The time to resolution of diarrhoea was shorter (P < .001) in the smectite group (median: 19.5 hours, interquartile range [IQR]: 13.5‐32 hours) compared with the control group (median: 53 hours, IQR: 31.5‐113.5 hours). The results of this study support the administration of smectite in the first‐line management of CID in dogs.  相似文献   

12.
IntroductionSystemic administration of tissue plasminogen activator (tPA) is seldomly reported in dogs and cats.AnimalsClient-owned animals receiving tPA (2010–2020).Materials and methodsMedical records of dogs and cats receiving tPA for distant known/suspected thrombus were reviewed. Fourteen dog visits (24 injections) and five cat visits (six injections) were included.ResultsCanine known/suspected thrombus included pulmonary thromboembolism (n=6), intracardiac thrombus (n=4), aortic thrombus (n=1), cranial vena cava thrombus (n=2), and femoral and iliac veins thrombus (n=1). Various canine primary diseases were represented, but open-heart surgery was the most common cause. Median time between diagnosis/suspicion of thrombus and tPA injection was 24.5 h (range, 3–150 h). Mean total tPA dose was 1.0±0.78 mg/kg.Clinical improvement occurred in 93% of dogs. Non-fatal complications were reported in 14% of dogs. Dogs’ survival to discharge was 78.6% without identifiable non-survivor characteristics. Feline known/suspected thrombus included unilateral feline aortic thromboembolism (FATE) (n=2), bilateral FATE (n=2), and right renal artery thrombus. Feline primary diseases included cardiomyopathy (n=5). Median time between diagnosis/suspicion of thrombus and tPA injection was 4 h (range, 2–17 h) and median total tPA dose was 1.0 mg/kg (range, 0.6–1.4 mg/kg).Clinical improvement occurred during 40% of the visits. All cats (n=3) with acute kidney injury (AKI) at admission developed worsening AKI and reperfusion injury. Of the remaining two visits, one developed a non-fatal AKI. Cats’ survival to discharge was 40%.ConclusionsSystemic thrombolysis with tPA seems to be effective and safe in dogs. More investigation is needed in cats.  相似文献   

13.
Azathioprine is a purine analogue used as an immunosuppressive and immunomodulator agent in various mammals, including cats. Several adverse reactions have been reported and have limited the use of the drug in the cat. Adverse reactions to azathioprine in humans have been correlated with reduced activity of thiopurine methyltransferase (TPMT) in erythrocytes. The purpose of this preliminary study was to determine if cats have TPMT activity in their erythrocytes and to compare the values obtained with the normal range for humans and the normal range for dogs in a preliminary report. Activity of the enzyme was measured in blood samples drawn from 41 cats. Blood also was taken from 5 dogs. The mean erythrocyte TPMT activity in the cats was 2.4 +/- 0.4 nmol (range, 1.2-3.9 nmol) per hour per milliliter of red blood cells (U/mL RBC) or 2-8 nmol per hour per gram of hemoglobin (U/g Hb). This range was far lower than the normal human range (8-15 U/mL RBC; 16-33 U/g Hb) and was of monopolar distribution. This observation apparently precludes any diagnostic purpose in assaying erythrocyte TPMT in this species. Erythrocyte TPMT activity in the 5 dogs ranged from 5.5 to 13.1 U/mL RBC (11-27 U/g Hb), which was comparable with normal and carrier ranges for humans, but proof of TPMT genetic polymorphism in either species will require genotyping studies.  相似文献   

14.
Three hundred seventeen specimens of urinary calculi of renal origin from 214 female dogs and 103 male dogs, and 71 specimens of urinary calculi of renal origin from 38 female cats and 33 male cats were submitted for mineral analysis between July 1, 1981, and December 31, 1993. Among dogs, 45 breeds were affected with renal calculi. Thirty-three breeds and a crossbred group were represented among females, but 8 breeds and the crossbred group accounted for 81% of the total. Among male dogs, 30 breeds and a crossbred group were represented, but 7 breeds and the crossbred group accounted for 69% of the total. Among cats, 10 breeds and a crossbred group were represented. Dogs and cats with renal calculi were older than those of 2 comparison population groups. More than one-half of the renal calculi in both dogs and cats were from the 1st known episode of urolithiasis. The risk of formation of renal calculi was found to be higher for cats than for dogs, when compared to other stone-forming cats and dogs (approximately 4.95 per 100 stone-forming cats and 2.88 per 100 stone-forming dogs). Among dogs, breeds at highest risk of developing renal calculi were Miniature Schnauzers, Shih Tzus, Lhasa Apsos, Yorkshire Terriers, and female Pugs. Also at high risk were male Dalmatians and male Basset Hounds. Among small dogs, females generally were at higher risk of developing renal calculi than were males. Regardless of size, terrier breed males generally were at higher risk of developing renal calculi. Breeds of dogs at low risk for development of renal calculi included crossbreds, German Shepherd Dogs, Labrador Retrievers, Golden Retrievers, and female Dachshunds. When only 1 kidney was involved, the risk of left renal calculus was greatest for both dogs and cats, but bilateral renal involvement was relatively common in both species (19% and 9%, respectively). Among dogs, specimens composed of 1 mineral substance (eg, struvite) occurred more often in males (58.3%) than in females (37.9%). Female dogs formed renal calculi containing struvite or oxalate more often than did males; males formed calculi containing urate more often than did females. Calculi containing oxalate, apatite, or some combination of these minerals predominated among cats; only 1 specimen from 38 female cats and only 4 specimens from 33 male cats contained neither oxalate nor apatite. Crossbred cats were significantly less likely to have renal calculi than were other breeds. A single renal calculus specimen was identified in several uncommon breeds including Tonkinese and Birman cats, and Affenpinscher, Clumber Spaniel, English Shepherd, and Field Spaniel dogs. No significant differences were observed between male and female dogs or between male and female cats with regard to mineral type of the specimen and the presence of urinary tract infection.  相似文献   

15.
Ciclosporin A (CsA) has potent immunosuppressive and immunomodulatory activity that has been exploited in human medicine to prevent the rejection of transplanted organs and to manage atopic dermatitis and psoriasis. Over the past decade, CsA has been employed more frequently in veterinary dermatology and its value in the management of several canine and feline dermatoses is now well established. CsA inhibits calcineurin phosphatase, suppressing T cell activation and the synthesis of T cell cytokines consequently impairing the activity of B cells, antigen-presenting cells, mast cells, basophils and eosinophils. The pharmacokinetics of CsA are similar in humans, dogs and cats and the drug has a wide safety margin in dogs, cats and rabbits. Adverse effects, principally transient vomiting and soft faeces/diarrhoea, may be seen shortly after instituting treatment but often resolve despite continuing treatment. Gingival hyperplasia and cutaneous effects such as hirsutism may occur after prolonged treatment.  相似文献   

16.
OBJECTIVE: To determine incidence rates and potential risk factors for vaccine-associated adverse events (VAAEs) diagnosed within 3 days of administration in dogs. DESIGN: Retrospective cohort study. ANIMALS: 1,226,159 dogs vaccinated at 360 veterinary hospitals. PROCEDURE: Electronic records from January 1, 2002, through December 31, 2003, were searched for possible VAAEs (nonspecific vaccine reaction, allergic reaction, urticaria, or anaphylaxis) diagnosed within 3 days of vaccine administration. Information included age, weight, sex, neuter status, and breed. Specific clinical signs and treatments were reviewed in a random sample of 400 affected dogs. The association between potential risk factors and a VAAE was estimated by use of multivariate logistic regression. RESULTS: 4,678 adverse events (38.2/10,000 dogs vaccinated) were associated with administration of 3,439,576 doses of vaccine to 1,226,159 dogs. The VAAE rate decreased significantly as body weight increased. Risk was 27% to 38% greater for neutered versus sexually intact dogs and 35% to 64% greater for dogs approximately 1 to 3 years old versus 2 to 9 months old. The risk of a VAAE significantly increased as the number of vaccine doses administered per office visit increased; each additional vaccine significantly increased risk of an adverse event by 27% in dogs < or = 10 kg (22 lb) and 12% in dogs > 10 kg. CONCLUSIONS AND CLINICAL RELEVANCE: Young adult small-breed neutered dogs that received multiple vaccines per office visit were at greatest risk of a VAAE within 72 hours after vaccination. These factors should be considered in risk assessment and risk communication with clients regarding vaccination.  相似文献   

17.
Zoledronate is a bisphosphonate frequently used for the treatment of hypercalcaemia of malignancy and tumour-associated bone pain in dogs, however, there is a paucity of information regarding its use in veterinary medicine. The aim of this retrospective study was to report the tolerability of zoledronate in the palliative treatment of cancer-bearing dogs and secondarily to to assess the efficacy of zoledronate for the treatment of hypercalcaemia of malignancy. Thirty-seven dogs (22 with tumour-associated bone pain and 15 with hypercalcaemia of malignancy) that received 114 zoledronate infusions were included. Tolerability was assessed by the absence of post-zoledronate hypocalcaemia or other adverse events as defined by Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events criteria. Efficacy was assessed by comparison of available ionized calcium levels before and after zoledronate administration in hypercalcaemic dogs. In 79% of zoledronate infusions, no adverse events were reported. The majority of adverse events which occurred in the other 21% of infusions could be attributed to concurrent chemotherapy or the underlying neoplastic disease. There was a small but significant increase in creatinine following treatment with zoledronate, however, none of the dogs developed clinically significant renal disease. In eight hypercalcaemic dogs with available ionized calcium following zoledronate administration, ionized calcium decreased rapidly within 7 days following treatment with zoledronate. Zoledronate is well-tolerated with few recorded adverse events, however, monitoring of serum creatinine is advised. Zoledronate seems to be effective in the treatment of hypercalcaemia of malignancy.  相似文献   

18.
Background – Few studies have investigated the frequency of urinary tract infection (UTI) in dogs receiving long‐term ciclosporin therapy. Hypothesis/Objectives – The goal of the study was to investigate the frequency of UTI in dogs receiving ciclosporin with or without glucocorticoids. A secondary goal was to determine whether bacteriuria, pyuria and urine specific gravity were good predictors of UTI, and if ciclosporin dose, concurrent ketoconazole therapy, sex or duration of therapy affected the frequency of UTI. Animals – Eighty‐seven dogs with various inflammatory skin disorders and 59 control dogs with inflammatory skin conditions that had not received glucocorticoids or ciclosporin for 6 months were enrolled. Methods – This study was retrospective. The first urine culture from dogs receiving ciclosporin was compared with control dogs using Fisher’s exact test. A logistic mixed model was used to test for association between a positive bacterial culture and duration of treatment, dose of ciclosporin, concurrent ketoconazole therapy and sex. The sensitivities and specificities for bacteriuria, pyuria and urine specific gravity were determined. Results – Twenty‐six of 87 (30%) ciclosporin‐treated dogs had at least one positive culture. Compared with 3% positive control samples, 15% were positive in treated dogs (P = 0.027). The sensitivity and specificity were, respectively, 64.1 and 98.1% for bacteriuria, 74.4 and 70.9% for pyuria, and 56.4 and 65.3% for urine specific gravity. All other analysed parameters were not significantly different. Conclusions and clinical importance – The results suggest that routine urine cultures and assessment of bacteriuria by cystocentesis should be part of the monitoring for dogs on long‐term ciclosporin with and without glucocorticoids.  相似文献   

19.
The aim of this study was to investigate the effect of bexagliflozin on glycemic control in poorly regulated diabetic cats and to evaluate for adverse events associated with this medication.Sodium-glucose cotransporter 2 inhibitors are a newer class of drugs used in the management of humans with type 2 diabetes mellitus. The objective of this study was to evaluate the effect of the orally administered drug, bexagliflozin in a group of poorly regulated diabetic cats over a 4-week study period. Five client-owned cats with poorly controlled diabetes mellitus receiving insulin therapy were enrolled. Bexagliflozin was administered once daily. Serum fructosamine, serum biochemistry profile, and 10-hour blood glucose curves were assessed at baseline (Day 0), Day 14, and Day 28. All cats had a significant reduction in insulin dose requirement (P = 0.015) and insulin was discontinued in 2 cats. There was a significant decrease in blood glucose concentration obtained from blood glucose concentration curves during the study period (P = 0.022). Serum fructosamine decreased in 4 of the 5 cats with a median decrease of 152 μmol/L (range: 103 to 241 μmol/L), which was not statistically significant (P = 0.117). No cats had any documented episodes of hypoglycemia. Adverse effects were mild. The addition of bexagliflozin significantly improved diabetic management in this group of cats.  相似文献   

20.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to control acute and chronic pain as well as to manage oncologic and neurologic diseases in human and veterinary patients. Despite ongoing research and efforts to improve the safety and efficacy of existing drugs, adverse effects such as gastrointestinal irritation, renal and hepatic toxicity, interference with hemostasis, and reproductive problems persist. The true incidence of NSAID-induced adverse effects in animals is unknown, but is likely underestimated, because cats and dogs may be more sensitive than humans to NSAIDs due to alterations in drug metabolism, absorption, and enterohepatic recirculation. NSAIDs produce both analgesia and toxic adverse effects primarily by inhibiting cyclooxygenase (COX), thereby decreasing the production of prostaglandins that signal inflammation and pain as well as mediate physiologic functions such as platelet aggregation, gastric protection, and electrolyte balance in the kidney. The presence of at least 2 COX isoforms may account for variability in NSAID efficacy and toxicity both within and among species. This paper reviews and evaluates the published literature on the safety, pharmacology, uses, and complications of a subclass of COX-1-sparing drugs, the coxibs, in veterinary medicine. Coxibs and other COX-1-sparing drugs provide a clinically useful improvement over traditional NSAIDs, but data are incomplete and more in vivo species-specific, target-tissue, and clinical studies are needed.  相似文献   

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