Evaluating the Effect of Infraorbital Region Taping Procedure on Patient Anxiety, Satisfaction, Edema, and Ecchymosis Level on Primary Septorhinoplasty.

AIM: This study aims to evaluate the effect of infraorbital region taping on patients' postoperative edema and ecchymosis, satisfaction levels, and anxiety during follow-up. METHODS: A total of 64 patients who underwent septorhinoplasty were included in this randomized controlled prospective study. According to the randomization list, the taping group's (TG) infraorbital region was taped with adhesive strips. Others were included in the control group and were classified as the nontaping group. Two blinded physicians evaluated the degree of edema and ecchymosis according to the photographs of patients taken on the first, second, fifth, and seventh postoperative days. Patient's appearance satisfaction was evaluated for ecchymosis levels. State anxiety inventory (STAI-S) and trait anxiety inventory (STAI-T) were used to measure preoperative and postoperative anxiety levels of patients. RESULTS: The degree of ecchymosis and edema were not significantly different except on the first day in the TG (P = 0.01, P = 0.01, respectively). Significant increment was found in the TG on first, second, and fifth days based on the satisfaction levels of patients for their appearance (P = 0.05, P = 0.03, P = 0.04, respectively). Preoperative STAI-S and STAI-T were similar for the groups (P = 0.78, P = 0.17, respectively). However, postoperative STAI-S of the TG were significantly lower compared with those of the nontaping group except seventh day (P < 0.05). CONCLUSION: Infraorbital taping did not decrease the edema and ecchymosis except on the first postoperative day. However, it had a significant ameliorating effect on patients' anxiety and satisfaction levels.

The effects of nasal base stabilization techniques on nasal tip rigidity.

BACKGROUND: The aim of this study was to compare the degree of nasal tip rigidity from different techniques for increasing nasal tip projection. METHODS: Retrospective records of patients who had undergone rhinoplasty were reviewed at the tertiary referral center. 81 patients who had undergone suturing of the medial crura to the extension graft or to the long septum were selected. In group A, fixation was performed at the same level compared to before surgery. In group B, tip grafting was performed to gain 3 mm or more in projection after fixation as done in group A. In group C, the same tip projection was provided by advancing the medial crura on the caudal septum or extension graft. Patients were evaluated with a visual analog scale, based on the rigidity of the nasal tip (0=very flexible, 10=very rigid). RESULTS: When the preoperative and postoperative VAS scores of all groups were compared, postoperative scores were significantly higher than the preoperative scores (p<0.001). The postoperative scores of group C were higher than those of the other groups. These differences were statistically significant (p<0.001). There was no statistically significant difference between groups A and B with regard to the postoperative scores (p=0.389). However, in group C, the increase between preoperative and postoperative scores was significantly higher than in the other groups (p<0.001). CONCLUSION: Advancing the medial crura on the caudal septum and suturing to gain 3 mm or more of tip projection may result in a more rigid nasal tip. Patients should be informed preoperatively of this potential result. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[The same nasal tip deformity in three siblings]. / Üç kardesteki ayni nazal tip deformitesi.

Similar to all other system anomalies, congenital nasal anomalies are caused by the defects during embriyogenesis and organogenesis. Nasal tip anomalies are usually accompanied by other systemic pathologies and syndromes. In this article, we report a nose anomaly with the same nasal tip appearance in three siblings.

The Use of Costal Cartilage in Rhinoplasty.

Autologous cartilage can be easily and safely harvested as a reliable source of cartilage in rhinoplasty through a small, well-hidden incision. Rib cartilage can be utilized during a primary rhinoplasty when there is insufficient cartilage from the septum or often in revisional nasal surgeries where the initial septal cartilage has previously been used or removed. Rib cartilage carving can be done on a cutting board prior to the beginning of the rhinoplasty in order to allow time for the cartilage to present any warping while it is soaked in saline. Overall autologous rib cartilage is a good source of copious and often good quality cartilage.

Oblique split technique in septal reconstruction.

The septum is considered to be the most important anatomical structure in providing nasal support. Because of a variety of potential etiologies nasal septum could be severely deformed or even diminished. Autogenous cartilage has generally been considered the gold standard grafting material in reconstructive septal surgery for creating the infrastructure of the nose. In the restructuring of the nasal skeleton autogenous cartilage can be harvested from the auricle or the rib. For the major septal problems requiring a large volume of tissues with severe structural defects costal cartilage is considered the best graft material. Apart from its advantages, warping has been the main problem with costal cartilage grafting. Oblique split method, provides straight costal cartilage grafts of varying thicknesses without the risk of warping. Segmental reconstruction of the L-strut with oblique split method, composed of dorsal and caudal struts, enables fine adjustment of height of the reconstructed septum.

Is pimecrolimus cream (1%) an appropriate therapeutic agent for the treatment of external ear atopic dermatitis?

BACKGROUND: In recent years, pimecrolimus 1% cream has been demonstrated to reduce symptoms of atopic dermatitis in patients when applied topically. MATERIAL/METHODS: In our study we compared the therapeutic effects of local 1% pimecrolimus to 1% hydrocortisone, and to a control group in a mouse model with atopic dermatitis in the external ear canals. Atopic dermatitis was created by application of Dinitrochlorobenzene in the external ear canals of mice. The development of atopic dermatitis was detected by clinical observation score and determination of total serum IgE levels. Pimecrolimus and hydrocortisone cream were topically applied to the external ear canal skin once a day for 14 days. RESULTS: There was no significant difference between the hydrocortisone and the pimecrolimus therapy groups, while there was a statistically significant difference between these 2 groups and the control group (p<0.05) Assessment of the clinical observation scoring carried out on the 14th day of therapy revealed that there was no difference between the hydrocortisone and pimecrolimus groups. Biopsies were taken on the 14th day following treatment. Tissue samples were histologically evaluated; contact dermatitis was observed microscopically in the control group, but in the therapy groups only minimal evidence of contact dermatitis was found. CONCLUSIONS: The results of our study reveal that the therapeutic efficacy of 1% pimecrolimus was equivalent to 1% hydrocortisone treatment in the artificially developed atopic dermatitis model in external ear canals of mice. These results clearly demonstrate that 1% pimecrolimus cream can be an effective alternative therapeutic agent in cases where steroid treatment proves to be insufficient or in cases where treatment must be discontinued due to its adverse effects.

Evaluation of the effectiveness of topical ciprofloxacin and prednisolone in the prevention of myringosclerosis.

An antibacterial drug, ciprofloxacin, has been reported to modulate the inflammatory and immune responses on monocytes. Our objective is to evaluate the effectiveness of ciprofloxacin in the prevention of myringosclerosis that is created by myringotomy in rats and to compare it with prednisolone. In this study, 24 healthy Sprague-Dawley type rats of age 3-4 months and 250-300 g weight were used. Rats have been divided into three random groups. Topical ciprofloxacin was administered to the rats in the first group and topical prednisolone was administered to the rats in the third group; no medication was applied to their opposite ears and they were determined as control group. Prednisolone was administered to one ear of the rats and ciprofloxacin was administered to their opposite sides in the second group. After bilateral myringotomies the treatments were applied for 20 days as five drops two times a day. Otomicroscopic examination was made on the 10th day and reperforations were made when necessary. Rats were killed on the 21st day and temporal bone dissections were done. When we evaluate in terms of myringosclerosis and tympanic membrane thickness, in the first group, myringosclerosis and thickness have been observed in two of seven ears (28.6%) where ciprofloxacin was administered and in five of the seven ears (71.4%) where no treatment was applied. In the second group where prednisolone and ciprofloxacin were compared, myringosclerosis and thickness have been observed in six of the ten ears (60.0%) where prednisolone was administered and in four of the ten ears (40.0%) where ciprofloxacin was administered. In the third group, myringosclerosis and thickness have been observed in three of seven ears (42.9%) where prednisolone was administered and in four of the seven ears (57.1%) where no treatment was applied. All histopathological evaluations were made by one pathologist in a blinded manner. In our study, the effect of the ciprofloxacin and prednisolone was similar in preventing the experimental myringosclerosis and TM thickness in rats. When compared with the control groups, this preventive effect was more obvious in the ciprofloxacin treatment group than that of prednisolone.

The effects of repetitious topical use of mitomycin C on antrostomy patency in maxillary antrostomy created rabbit model.

The aim of our study was to investigate the effect of the topical use of mitomycin C (MMC) intraoperatively in single dose and intra-postoperatively in two doses on the narrowing of antrostomy in maxillary rabbit sinus antrostomies created experimentally. And also to determine the local and systemic side effects of topical MMC. With this objective, 0.6 mg/ml MMC was used to the first group at single dose and to the second group intraoperatively and on third day postoperatively in two doses topically for 5 min. After 8 weeks, although the mean area of antrostomy was larger than that in the control side in the first group, which received single dose MMC, the difference was not statistically significant (p = 0.287). The second group received two doses, and the antrostomy areas were found to be significantly larger than the controls (p = 0.05). Overall, the sides that received MMC were significantly larger (p = 0.029). From the point of histopathological examination of the tissue, it was seen that two-dose MMC increased the edema indicating inflammation and antrostomy resolved with normal respiratory tract epithelium. It was shown by measuring the blood values that nephrotoxic and myelosupressant effect of MMC occurring in systemic use did not occur with single or double dose topical use. Our results demonstrate that even if the number of cases was low, two doses of topical MMC usage prevent the narrowing of antrostomy while single dose MMC does not. And two-dose topical MMC usage does not have local and systemic side effects.

Is there any relationship between the frontal cell and the Agger nasi cell and the localization of the anterior ethmoid artery?

OBJECTIVES: In this article, we examined the effect of the presence or absence of a frontal cell or an Agger nasi cell on the localization of the anterior ethmoid artery. PATIENTS AND METHODS: Coronal paranasal sinus computed tomography scans on 110 sides of 61 patients (35 males, 26 females; mean age 35.6 ± 12.7 years; range 15 to 72 years) who underwent surgery for septal deviation, concha bullosa, antrochoanal polyp between September 2006 and February 2008 were retrospectively evaluated and the anterior ethmoid foramen localization was measured according to the anterior nasal spine. The correlations of these measurements with the presence and absence of a frontal cell and an Agger nasi cell were investigated. RESULTS: The measurement of the anterior ethmoidal foramen according to anterior nasal spine was 18.2 ± 8.8 mm in the absence of an Agger nasi cell and was 20.3 ± 6.6 mm in the presence of an Agger nasi cell. This distance was measured as 20.0 ± 7.3 mm when the frontal cell was not determined. This measurement was 20.2 ± 6.5 mm in the presence of a frontal cell. According to the frontal cell types the results of the measurements were 20.5 ± 5.9 mm, 18.9 ± 8 mm, 20.6 ± 7.3 mm, for type 1, type 2 and type 3, respectively. Our results revealed that there were no significant relationship between the presence or absence of a frontal cell and an Agger nasi cell and the localization of the anterior ethmoidal foramen. CONCLUSION: The results of this study showed that the presence or absence of these cells does not affect localization of the anterior ethmoid artery.

A unique case of a postrhinoplasty epidermoid cyst.

The first case of a postrhinoplasty cyst lined with unusual stratified squamous epithelium, unlike the other published mucous ones, is described in this article. There are two different theories accounting for this complication: namely mucosal herniation and the free graft theory. Although the cyst was very close to the marginal rim incision, there was no connection between the cyst and vestibuler skin. Thus the free graft theory is more logical than the herniation theory to explain the development of this cyst.

[An unusual localization of fungiform papilloma].

In this article, we presented a 54-year-old male who was admitted with complaints of nasal obstruction with snoring and mouth breathing for one year. Anterior rhinoscopy revealed a mass arising from the inferior nasal concha on the left side. After computed tomography evaluation, endoscopic examination and incisional biopsy, the mass was removed en bloc endoscopically. The histopathological analysis resulted in a diagnosis of a fungiform papilloma. Fungiform papillomas arise almost exclusively on the nasal septum, while inverted papillomas predominantly affect the lateral nasal wall. To our knowledge, no previous report of fungiform papilloma involving the inferior concha has been published in the English literature.

Effectiveness of caudal septal extension graft application in endonasal septoplasty.

INTRODUCTION: Septal deviation is a common disease seen in daily otorhinolaryngology practice and septoplasty is a commonly performed surgical procedure. Caudal septum deviation is also a challenging pathology for ear, nose, and throat specialists. Many techniques are defined for caudal septal deviation. OBJECTIVE: To evaluate the effectiveness of caudal septal extension graft (CSEG) application in patients who underwent endonasal septoplasty for a short and deviated nasal septum. METHODS: Forty patients with nasal septal deviation, short nasal septum, and weak nasal tip support who underwent endonasal septoplasty with or without CSEG placement between August 2012 and June 2013 were enrolled in this study. Twenty patients underwent endonasal septoplasty with CSEG placement. The rest of the group, who rejected auricular or costal cartilage harvest for CSEG placement, underwent only endonasal septoplasty without any additional intervention. Using the Nasal Obstruction Symptom Evaluation (NOSE) and Rhinoplasty Outcome Evaluation (ROE) questionnaires, pre- and post-operative acoustic rhinometer measurements were evaluated to assess the effect of CESG placement on nasal obstruction. RESULTS: In the control group, preoperative and postoperative minimal cross-sectional areas (MCA1) were 0.44±0.10cm2 and 0.60±0.11cm2, respectively (p<0.001). In the study group, pre- and postoperative MCA1 values were 0.45±0.16cm2 and 0.67±0.16cm2, respectively (p<0.01). In the control group, the nasal cavity volume (VOL1) value was 1.71±0.21mL preoperatively and 1.94±0.17mL postoperatively (p<0.001). In the study group, pre- and postoperative VOL1s were 1.72±0.15mL and 1.97±0.12mL, respectively (p<0.001). Statistical analysis of postoperative MCA1 and VOL1 values in the study and the control groups could not detect any significant intergroup difference (p=0.093 and 0.432, respectively). In the study group, mean nasolabial angles were 78.15±4.26° and 90.70±2.38°, respectively (p<0.001). CONCLUSION: Endonasal septoplasty with CESG placement is an effective surgical procedure with minimal complication rate for subjects who have a deviated, short nasal septum and weak nasal tip support.

Does helicobacter pylori have a role in the etiology of adenoid hypertrophy?

To investigate whether there is any association between nasopharyngeal reflux and adenoid hypertrophy in children by using 24-h pH monitoring with dual probe and to determine whether Helicobacter pylori simply colonises in adenoid tissue or it is present there temporarily due to extraesophageal reflux. A prospective study at a tertiary referral center. Thirty-two patients who underwent adenoidectomy, aged ranged between 4 and 13 were included. All children with adenoid hypertrophy underwent 24-h pH monitoring with a dual probe. Proximal probe was placed in the nasopharynx. The presence of nasopharyngeal reflux and gastroesophageal reflux were investigated by 24-h pH monitoring. The presence of H. pylori was investigated in adenoidectomy samples by HP-fast test. Of the 32 patients who underwent adenoidectomy, 5 had nasopharyngeal reflux positivity while 27 patients did not show nasopharyngeal reflux positivity with pH monitorisation. Helicobacter pylori could not be detected in 5 nasopharyngeal reflux positive children while 3 of 27 nasopharyngeal reflux negative children showed H. pylori positivity, one of them in the mucosa and others in the core. This study demonstrated the high incidence of nasopharyngeal reflux and gastroesophageal reflux in adenoid hypertrophy and the possible colonisation of H. pylori in the adenoid tissue. This may change the assesment of children with adenotonsillar hypertrophy in near future. However, more placebo controlled and double blind studies and larger series are still needed to support this hypothesis.

The use of glass ionomer cement in the reconstruction of the dorsal L-strut: an experimental study on rabbits.

OBJECTIVES/HYPOTHESIS: This experimental study in a rabbit model aimed to investigate the use of glass ionomer cement as a tissue adhesive on the dorsal L-strut. STUDY DESIGN: Sixteen adult male New Zealand White rabbits were used. The rabbits were equally divided into two groups as the control and the study groups. METHODS: The nasal septum was exposed through a superior approach. A graft was harvested preserving an L-strut cartilage. In the control group, a vertical incision was performed on the dorsal part of the L-strut to divide it into two cut ends, and the graft was sutured to the cut ends with 5-0 polydioxanone suture. In the study group, the reconstruction of the dorsal L-strut was made by fixing the graft to the cut ends with glass ionomer cement as the tissue adhesive. At 2 months, the rabbits were sacrificed. The nasal septum was removed for histopathological examination. RESULTS: No foreign body giant cells or acute inflammation were determined in the rabbits. The study group had less pronounced chronic inflammation. Comparison of the groups revealed that parameters regarding vascularization, cartilage proliferation, and new cartilage cells were statistically significant different between the two groups (P = .010, P = .010, P = .028, respectively). More vascularization, cartilage proliferation, and new cartilage cells were seen in the study group. CONCLUSIONS: Glass ionomer cement was effective for the reconstruction of the dorsal L-strut without any foreign body reaction, cartilage necrosis, or marked inflammation in rabbits, and it may be a potentially beneficial alternative to suture fixation.

The oblique split method: a novel technique for carving costal cartilage grafts.

IMPORTANCE: Autogenous rib cartilage is widely used in the septorhinoplasty cases with major structural grafting requirements. However, there is a risk of warping over time. OBJECTIVE: To introduce a novel method for carving costal cartilage grafts to obtain straight grafts of varying thicknesses and to eliminate the risk of warping. DESIGN: Between 2007 and 2011, a total of 43 consecutive patients underwent septorhinoplasty using autogenous costal cartilage grafts carved by the oblique split method (OSM). SETTING: The Ankara Training and Research Referral Hospital, Ankara, Turkey. PARTICIPANTS: The study included 43 patients with saddle nose deformity and revisional rhinoplasty with a depleted source. All patients were followed-up for a period ranging from 12 to 37 months (mean, 19.2 months) after surgery. INTERVENTIONS: All patients underwent open or closed septorhinoplasty. Autogenous costal cartilage was carved with the OSM to obtain grafts suitable for use as columellar strut, dorsal onlay, L-strut, lateral crural strut, caudal extension, and tip or speader grafts in selected cases. MAIN OUTCOME MEASURES: Patients were evaluated by inspection, palpation, and photographic documentation before surgery. Inspection, palpation, and photographic documentation were carried out every 6 months and 12 months after surgery and once a year thereafter. RESULTS: Patient satisfaction in terms of form and function was achieved in 41 patients (95%). Two patients required reoperation for further tip projection (n=1) and alar batten graft displacement (n=1). No complication was observed as a result of graft warping, resorption, or fracture. CONCLUSIONS AND RELEVANCE: The OSM provides straight costal cartilage grafts of varying thicknesses without the risk of warping. Because they strictly preserve their straight form, the grafts may safely be modified into rectangular shape or carved asymmetrically and/or have their edges beveled. Current data from this study suggest that the OSM offers a flexible and reliable reconstructive option for the rhinoplasty surgeon. LEVEL OF EVIDENCE: 4.

Is there any effect of coenzyme Q10 on prevention of myringosclerosis? Experimental study with rats.

UNLABELLED: Recent studies have shown that the formation of myringosclerosis could be reduced by the application of antioxidant enzymes and elements. OBJECTIVE: The aim of this study was to investigate the effectiveness of coenzyme Q10 on the prevention of experimentally induced myringosclerosis. METHOD: Forty-eight healthy female wistar albino rats were bilaterally myringotomized and divided into four groups randomly. Group A received no treatment, group B was administered oral coenzyme Q10. Group C was treated with topical saline solution, group D received topically coenzyme Q10. On the 15th day of treatment, tympanic membranes were examined by otomicroscopy. Myringosclerotic lesions were documented semiquantitatively by using 4-point scale. After harvesting tympanic membranes were evaluated histopathologically. RESULTS: In group D (topical coenzyme Q10), we observed otitis within the first four days of the study and this group was excluded from the study. Regarding otomicroscopic examinations, there were no significant differences among groups in myringosclerosis formation (p = 0.241). When group A (non treatment) compared to groups B and C regarding histopathologic examination, the results demonstrated statistical significant differences (p = 0.004; p < 0.001), respectively. There was no statisticaly significant difference between groups B and C (p = 0.160). CONCLUSION: Oral administration of coenzyme Q10 did not reduce myringosclerosis formation in myringotomized rats.

Is there a relationship between serum levels of vitamin a, vitamin e, copper and zinc and otitis media with effusion in children?

The aim of this study is to determine whether the serum levels of vitamin A, vitamin E, copper and zinc have a role in the development of otitis media with effusion (OME) in childhood. This prospective study was conducted between February 2010 and February 2011 at a tertiary Otorhinolaryngoloy Clinic. There were 113 subjects and subdivided into three groups. Group 1 consisted of 44 patients who underwent adenoidectomy with ventilation tube placement due to OME. Group 2 consisted of 43 patients underwent adenoidectomy alone and group 3,called control group, included 26 healthy children. Serum values of vitamin A, vitamin E, copper and zinc were measured preoperatively. Comparison of the patient groups showed that group 1 patients had significantly lower serum zinc levels than group 2 patients (p = 0.002), although differences between both patients groups and controls were not significant. We found that the differences among the three groups in terms of serum levels of vitamin A, vitamin E and copper were not statistically significant (p > 0.05). The results of this study showed that serum levels of vitamin A, vitamin E and copper may not play a role on development of OME. We postulated that high serum zinc status may have the preventive effect in the predisposition to OME which may related to adenoid hyperplasia.

Sneezing and runny nose: should allergy testing be routinely performed?

The need for routine determination of rhinitis subtypes by allergy testing and the relevance between symptoms and allergy were evaluated. A retrospective study at a tertiary hospital, ENT clinic. One hundred and twenty-seven adult patients with sneezing and runny nose for at least 6 months for the last two consecutive years were included. The age range was 16-60. Allergy testing was only positive in 43.4% of the patients. Excluding mixed rhinitis, persistent sneezing and runny nose were mostly related to anatomical deformities, mainly septal deviation followed by vasomotor rhinitis. Persistent sneezing and runny nose may be caused by different etiologies other than allergy. Determination of rhinitis subtypes is important for accurate treatment of patients with these symptoms. Taking appropriate medical history and performing a good physical exam with objective allergy testing are highly recommended.

Antioxidant role of selenium in rats with experimental acute otitis media.

The aim of this prospective experimental animal study was to determine whether selenium had a protective effect on oxidative stress in rats with acute otitis media, by measuring the alterations of antioxidant parameters and lipid peroxidation on days 4 and 10 after inoculation into the middle ear. Streptococcus pneumoniae was inoculated into the middle ear cavities of 32 rats in animal laboratory of a tertiary medical center. Group 1 served as the control group and the animals were administered 1.5 ml/day saline. Group 2 received 0.2 mg/kg/day oral selenium for 10 days. The blood samples of each group were obtained on post-inoculation days 4 and 10. The levels of thiobarbituric acid reactive substances, albumin, total sulphydryl, superoxide dismutase and glutathione peroxidase were investigated. Day 10 level of thiobarbituric acid reactive substance in group 2 was lower than the day 4 level of the same substance in the control group. Although glutathione peroxidase and superoxide dismutase levels significantly decreased starting from 4th day until 10th day in group 1, their levels increased in group 2. Day 10 levels of albumin and total sulphydryl in group 1 were significantly higher than day 4 levels in group 2. We found that selenium supplementation for 10 days decreased thiobarbituric acid reactive substances and increased glutathione peroxidase and superoxide dismutase levels when compared to the control group. We believe that selenium supplementation may be beneficial to prevent the clinical sequelae and recurrence of otitis media.

Are systemic voriconazole and caspofungin ototoxic? An experimental study with rats.

OBJECTIVES: To determine whether systemic administration of voriconazole and caspofungin causes ototoxicity. METHODS: This study was conducted on 32 healthy male Wistar albino rats. The baseline auditory brainstem response (ABR) thresholds of all animals were obtained under general anesthesia. Then, the rats were randomly divided into 4 groups (groups I-IV), each group consisting of 8 rats. Rats in group I were injected intraperitoneally with voriconazole 10 mg/kg/day for 7 days, and the rats in the group II were injected intraperitoneally with caspofungin 5 mg/kg/day for 7 days. Group III received 120 mg/kg/day gentamicin for 7 days. Group IV received saline for 7 days. The animals were then observed for 7 days, and on 14th day of the trial, posttreatment ABRs of both ears were recorded. RESULTS: We did not find any significant differences between pretreatment and posttreatment median ABR thresholds in the voriconazole, caspofungin, or saline groups. In the gentamicin group, there was a statistically significant difference between pretreatment and posttreatment ABR thresholds. CONCLUSION: Caspofungin and voriconazole did not change ABR thresholds in speech frequencies after a 7-day-period of their administration. We believe that further animal studies must be performed after administration of these agents for a longer time period, and these findings must be consolidated with histopathological investigations.