Investigation of topical ciprofloxacin ototoxicity in guinea pigs

Antibiotic eardrops mostly contain potentially ototoxic aminoglycosides. Ciprofloxacin is an alternative, and there is limited experience in its topical use. To investigate the topical ototoxicity of ciprofloxacin, 11 guinea pigs have been operated on. Transbullae silicone drug delivery tubes were placed to both ears of the animals. After the operation the guinea pigs were divided into two groups. The first group of animals received 0.2 ml of 4% gentamicin in one ear and 0.2 ml of 0.9% sodium chloride solution in the other. The second group received 0.2 ml of 0.2% ciprofloxacin in the test ear and 0.2 ml of 0.9% sodium chloride solution in the control ear. All drugs were given once a day on 7 consecutive days. Auditory brainstem response thresholds were recorded using click, 4 and 8 kHz logon stimuli before and after the operation, and after topical drug application. Results were statistically compared using Wilcoxon matched pairs signed-ranks test. Comparison of the thresholds before and after the operation, physiological saline application, as well as ciprofloxacin application yielded no statistically significant differences, whereas application of gentamicin resulted in total hearing loss. The results indicate that topical use of 0.2% ciprofloxacin is not ototoxic in guinea pigs.     

Influence of the gas exchange function through the middle ear mucosa on the development of sniff-induced middle ear diseases

To investigate the influence of gas exchange function through the middle ear mucosa on the development of sniff-induced middle ear diseases, the authors examined the mastoid pneumatization among patients with sniffing habit using computed tomography, and also examined the change of negative middle ear pressure induced by sniffing using tympanogram. In 20 ears with cholesteatoma or adhesive otitis media, the areas of mastoid cavity measured at the level of the lateral semicircular canal were significantly smaller than those in 26 ears with otitis media with effusion (OME) or attic retraction and in eight normal ears with sniffing habit (P < .01 and P < .0001, respectively). In 26 ears with OME or attic retraction, the areas of mastoid cavity were significantly smaller than those in eight normal ears with sniffing habit (P < .0001). By contrast, in the four ears with sniff-induced middle ear disease, the recovery of negative middle ear pressure in 5 minutes without swallowing was less than 10 mm H2O, whereas in all seven ears with normal eardrum, negative middle ear pressure recovered by more than 20 mm H2O in 5 minutes. These findings suggested that impairment of gas exchange function through the middle ear mucosa, as well as eustachian tube dysfunction, might be closely related to the development of sniff-induced middle ear diseases.     

Elements in the choice of a technic for female sterilization]

This experiment determined whether overt performance of the entire response (actual running) was necessary for the conditioning of methylphenidate-induced locomotor activity (wheel-running) in guinea pigs. Four guinea pigs were given daily injections of 2.5 mg/kg methylphenidate and were allowed to run in activity wheels; 4 other guinea pigs were given methylphenidate and were placed in locked activity wheels; a third group of 4 guinea pigs were administered saline and allowed to locomote; a fourth group of 4 guinea pigs received saline injections and were placed in locked activity wheels. After 12 days of injection, all animals were given saline injections on the 9 subsequent days and allowed to run freely in the wheels. The 2 groups which had received methylphenidate showed more locomotor activity than the saline injected animals but were not distinguishable from each other on the basis of prior opportunity to engage in locomotor activity. These results were interpreted to indicate that (a) increased methylphenidate-induced locomotor activity may be conditioned with repeated administration of the drug, and (b) actual running is not essential for the conditioning of drug-induced wheel-running.     

The role of cardiac troponin T and other new biochemical markers in evaluation and risk stratification of patients with acute chest pain syndromes

Electrocochleography (ECochG) was used to evaluate cochlear function in guinea pigs with experimentally induced endolymphatic hydrops (ELH) before and after osmotic dehydration with either glycerol or urea. We surgically induced ELH in the right ears of 9 guinea pigs, while the right ears of 6 guinea pigs received a sham operation. The left ears of the 15 animals constituted the normal group. Eight weeks after surgery, summating potential (SP) and action potential (AP) amplitudes were measured prior to and following the administration of glycerol or urea. The SPs and SP/AP ratios were reduced in all groups, with no significant differences among groups or between dehydrating agents. Some of the hydropic ears, however, did show an increased AP threshold and a recruitment effect. In measurements from 6 additional animals, serum osmolarity increased more with urea than with glycerol. The guinea pig model remains valuable for investigation of ELH, even though it differs in significant respects from ELH in humans.     

Pathology and pathogenesis of mucoviscidosis (author''s transl)

The section of the cat's mesotympanum, denuded of mucosa, to Silastic and gelatin film was studied and compared with the contralateral control ear, which was also denuded of mucosa. The ears were studied by horizontal pathological sections taken one, two, four, and six months post-lympanotomy and insertion of either gelatin film or Silastic. The Silastic, gelatin film and control ears were compared for inflammatory reaction, amount of fibrosis, and the quality and quantity of mucosal regeneration. The inflammatory reaction was increased in the ears with Silastic compared with their corresponding control ears or to the ears with gelatin film. The amount of fibrosis and the quality and quantity of mucosal regeneration was essentially the same in the Silastic, gelatin film, and control ears. This study shows that both substances are well tolerated in the middle ear and that neither substance stimulated or inhibited the regrowth of mucosa or fibrous tissue when compared with the control.     

Middle ear gas composition and middle ear aeration

Partial pressures of the gases in the middle ears of 14 guinea pigs were measured continuously on-line with a specially designed mass spectrometer. The average values were carbon dioxide 67.55 mm Hg, oxygen 48.91 mm Hg, and nitrogen 596.54 mm Hg. These values confirm earlier measurements and show that the gas composition of the middle ear differs basically from that of air and resembles that of venous blood. These findings are indicative of bilateral diffusion between the middle ear cavity and the blood. We propose that under physiologic as well as under pathologic (ie, atelectatic) conditions, the gas content of the middle ear is also controlled by diffusion. This mechanism fits well with the fluctuating character of atelectatic ears. Thus, a negative middle ear pressure could be secondary to excessive loss of gases through increased and excessive diffusion, although additional mechanisms are probably also involved. A likely contributing factor is poor pneumatization of the mastoid, with consequent absence of a physiologic pressure regulation mechanism by its pneumatic system.     

5-year series of constricted (lop and cup) ear corrections: development of the mastoid hitch as an adjunctive technique

Despite the multitude of corrective procedures described, adequate surgical correction of the congenital constricted ear remains a challenge. The maintenance of the shape and elevation of the reconstructed upper neohelix poses a particular problem. In the present series, experiences with lop ear correction utilizing standard techniques and the use of the mastoid hitch as a useful adjunct to these procedures are described. A total of 19 ears were reconstructed. There were three type 1, eight type 2a, seven type 2b, and one type 3 deformities (Tanzer classification). A graded sequence of procedures was adopted. Mild deformities were corrected by cartilage scoring techniques; a V-Y advancement of the helical root was added for moderate deformities. Cartilage expansion by a banner flap was required for more severe deformities. A mastoid hitch, whereby the refashioned upper neohelix is sutured to the mastoid fascia, should be used as an adjunct to these procedures to maintain helical elevation and prevent recurrence. Severe type 3 deformities may require autologous auricular reconstruction. Mean follow-up time was 1 year. There were six excellent, seven good, four fair, and two poor results. Two patients who had not had mastoid hitch procedures developed a recurrence of the lop deformity. Adequate surgical correction of constricted ear deformities requires a variety of surgical techniques. The mastoid hitch being used for constricted ear correction has not been described elsewhere. The mastoid hitch is a useful adjunctive procedure that may be used effectively in combination with other procedures.     

The use of homograft stapes

Homograft stapes were used for ossicular reconstruction in 43 ears over a three-year period. The average hearing improvement was 7.9 db. These cases were divided into groups: those with an intact posterior canal wall and those with an open mastoid cavity. The latter group fared better, with an average improvement of 15 db. Fourteen of the 43 ears were subsequently re-explored. Satisfactory bony union between the homograft stapes and recipient footplate was found in eight cases, four cases showed poor bony union, and bony resorption of the homograft had occurred in two patiemise for reconstruction of the ear with a loss of the stapes arch, especially in the presence of an open mastoid cavity and thus a shallow middle ear.     

Effects of nasal packing on eustachian tube function

Eustachian tube function was assessed by tympanometry in 47 patients (94 ears) with anterior nasal packing placed after nasal surgery and in 12 patients (24 ears) requiring anterior and posterior packing for epistaxis. Twenty-four of the 94 ears (25.5%) in patients with anterior packing exhibited reductions in middle ear pressure (greater than or equal to --100 mm H2O), whereas 12 of 13 ears (92.3%) ipsilateral to and six of 11 ears (45.4%) contralateral to the posterior pack demonstrated comparable reductions in middle ear pressure. The observation that posterior packing is associated with a greater incidence of eustachian tube dysfunction than anterior packing suggests that the mechanism of this dysfunction may be related to stasis in the peritubal lymphatic plexus rather than to nasal obstruction per se.     

Gas exchange function of the middle ear in patients with otitis media with effusion

Gas exchange function through the middle ear mucosa was assessed using nitrous oxide (N2O) in patients with otitis media with effusion (OME), as well as in normal ears during elective surgery for unrelated disorders. In all normal ears except one (n = 43), an increase in pressure was observed after N2O inhalation. In 42 of 84 ears with OME, a pressure increase was observed, but not in the remaining 42 ears (50%), indicating that the gas exchange function in these latter ears was impaired. In 21 of the 42 ears showing no middle ear pressure increase following N2O inhalation, the middle ear pressure was again monitored after myringotomy and aspiration of the effusion A pressure increase was found in 16 ears, indicating that the impairment in gas exchange function in ears with OME may be reversible in most cases. Computed tomography of the mastoid was examined preoperatively in 66 ears, with the presence or absence of a middle ear pressure change well correlated in 57 ears with the presence or absence of mastoid aeration.     

Experimental perilymphatic fistula

The round window membrane of the inner ear of 15 guinea pigs was removed under ketamine anaesthesia. Perilymph was aspirated through the round window in 8 guinea pigs. The round window membrane had regenerated spontaneously after 2 weeks. Light microscopy revealed hair cell loss localized to the apical and basal turns of the cochlea. Morphological examinations showed the most severe changes in these group of aspirated animals. Abrupt pressure imbalance may be a causative factor of sensorineural hearing loss.     

Acute cardiovascular toxicity of thallium (I) ions

The paper deals with: 1. the protein concentration in the perilymph (PL), the serum and the cerebrospinal fluid (CSF), 2. the protein pattern in the PL and 3. histological findings in the middle and inner ear in unilaterally ear-infected guinea pigs. The studies were performed 6 h to 21 days post infectionem (Fig. 1). The pathological changes in the middle ear, which, in most cases, were limited to the infected ear, were initially evaluated under the operating microscope and divided into 4 stages. The analytical and histological results were presented as functions of these stages. As the inflammation intensity increased, the protein concentration in the PL of the infected ears increased to a level exceeding that of the normal value more than ten times (Fig. 2). However, in the serum and in the CSF this concentration remained unchanged. Likewise, no significant protein increase in the PL of the contralateral ears was detectable in most cases. As the inflammation intensity increased, the number of the precipitation lines detectable immunoelectrophoretically increased in the PL of the infected ears (Fig. 3). An increase in the alpha1- and gamma-globulins and a decrease in Albumin was found by electrophoresis on cellulose acetate strips (Tab. 3). The histological findings correlated with initially established inflammatory stages of the middle ear mucous membrane (Tab. 4). As the inflammation intensity increased, the round window, too, was changed pathologically, so that in some cases of purulent otitis media middle ear secretion could enter the cochlea. The protein increase in the PL immediately after the infection is probably due to an increase in the blood vessel permeability in the inner ear.     

The guinea pig as a model for the study of maternal immunization against respiratory syncytial virus infections in infancy

Maternal immunization might protect infants from severe disease due to respiratory syncytial virus (RSV). Guinea pigs are susceptible to infections with RSV and transfer antibodies to their offspring prenatally. Pregnant guinea pigs were immunized by infection with RSV and their offspring were challenged intranasally with RSV. Pulmonary viral replication was compared among the pups born to immunized mothers (group A) and the pups from nonimmune mothers (group B) in two studies. Mean (+/-SD) log10 virus titers were, in study 1, group A, 2.3 +/- 0.8 pfu/g of lung (n = 10); group B, 3.6 +/- 1.5 pfu/g (n = 13) (P = .0058); and study 2, group A, < 1.69 pfu/g (n = 8); group B, 3.4 +/- 0.9 pfu/g (n = 6) (P = .0002). Thus, immunization of pregnant guinea pigs resulted in a significant reduction in viral replication in the lungs of their offspring. Guinea pigs should be useful for the study of maternal immunization against RSV.     

Prefabrication of mucosa-lined flaps: a preliminary study in the pig model

There is a need in reconstructive surgery for flaps lined by nonkeratizing stratified squamous epithelium or mucous membrane. Applications could be found in nasal, oral, genital, and esophageal reconstruction and even in reconstruction of hollow intra-abdominal tubes. Prefabrication of lined flaps has so far been limited to a pretransfer grafting of split-thickness skin. However, in certain situations this does not satisfy the primary requirement of replacing "like with like." Also, the availability of donor sites for harvesting mucosa is limited. The present study involves prefabrication of mucosa-lined flaps without causing donor site morbidity. The study was carried out on six mini-Hartford pigs. Buccal mucosa was harvested from the cheeks; the sheet was divided into several smaller graft pieces of 1 to 2 cm2 area. These graft pieces were then applied to the deep fascia at a distance of 5 to 15 mm from one another, also to galea, and to the undersurface of skin flaps. The grafted area was isolated from the opposing surface with a silicone sheet or Marlex mesh. The grafts were allowed to take and, it was hoped, merge together to form a sheet graft of dimensions greater than those of the original. Two to 7 weeks after the initial grafting, the skin flap was elevated; the mucosal grafts were observed macroscopically for take and surface area and microscopically to confirm that the lining was indeed mucosa. The mucosa took well on both the fascia and galea and also on the undersurface of the skin; it enlarged in size, and the small pieces became confluent to form a single sheet. The increase in surface area varied from 33 percent at 11 days postgrafting to a maximum of 238 percent after 7 weeks. All pigs had positive cultures from the mucosa before implantation but only one developed gross infection leading to partial graft loss.     

Experimental studies on acute and chronic action of azelastine on nasal mucosa in guinea pigs, rats and dogs

Azelastine (CAS 37932-96-0) nasal spray (Allergodil, Rhinolast, Astelin) was investigated in acute experiments in guinea pigs and after a 26-week local application period with daily repeated administration for effects on ciliary beat activity (acute experiments) and morphology of nasal mucosa. The commercially available spray did not inhibit ciliary beat activity in guinea pigs nor did it cause any inflammatory or atrophic changes after 26-week daily local application on nasal mucosa in rats and dogs.     

Safety of silver oxide-impregnated silastic tympanostomy tubes

Otorrhea occurs after the insertion of tympanostomy tubes in as many as 50% of ears. Although topical antibiotic solutions minimize otorrhea in the immediate postoperative period, recurrent otorrhea is sometimes a clinical problem. The antimicrobial effects of silver oxide when impregnated into a tympanostomy tube may decrease the incidence of recurrent otorrhea. This study demonstrates that silver oxide-impregnated silicone elastomer is well tolerated within the middle ear of gerbils when implanted for 1 year, and the tissue reaction is no more than silicon elastomer without silver oxide. When applied directly to the round window of guinea pigs, there was no evidence of ototoxicity of silver oxide as measured by electrocochleography (N-1 thresholds) and cytocochleography (hair cell counts). These animal studies indicate that silver oxide-impregnated silicone elastomeric tympanostomy tubes may be used safely in clinical trials to determine efficacy.     

Auricular reconstruction with a postauricular myocutaneous island flap: flip-flop flap

Surgical defects of the concha-helix part of the ear larger than 2 cm may pose a reconstructive challenge. Split- or full-thickness skin grafts or local flaps may be used, and a number of these have been described. Yet cosmetic results are often unsatisfactory. Our experience with a postauricular myocutaneous island flap is described. Eleven patients (12 ears), aged 48 to 89 years, underwent the procedure under local anesthesia following excision of conchal bowl malignant tumors that included the cartilage underlying the skin. The surgical technique is described in detail. Few complications were encountered, and cosmetic results were excellent. In four ears, resection margins extended into the ear canal, and that portion was allowed to heal satisfactorily by secondary intention. We recommend the use of this flap for practical, safe, and early good cosmetic results.     

Experimental models of nasal hypersensitive reaction

An experimental animal models of nasal hypersensitive reaction had been developed in twelve guinea pigs by intranasal applications of 2.4-toluene diisocynate (TDI). Symptoms, morphological appearance of the nasal mucosal scrapings and tissue pathology were studied, and the histamine content in the turbinates evaluated. The results showed a typical picture of nasal hypersensitive reaction. A plenty of eosinophils and mast cells was found on the surface of the nasal mucosa. A marked infiltration of the eosinophils was seen not only in the subepithalial connective tissue but also in the epithelial layer and in the enlarged venous vessels. Significantly higher levels of histamine were detected in the mucosa from TDI treated animals than in control animals (P < 0.01). We consider the experimental models to be ideal.     

Xenograft versus autograft in tympanoplasty

This retrospective study compares the tympanoplasty success rate when using a xenograft (Zenoderm) or an autograft (temporalis fascia). Fifty-three ears were operated on over a three-year period. All the tympanoplasty operations were performed by the same surgeon. There were 43 ears in the temporalis fascia autograft group and 10 ears in the Zenoderm xenograft group. Both groups were similar with respect to patient age, type of tympanoplasty, area of tympanic membrane perforation and condition of the contralateral ear. The tympanoplasty success rate in the temporalis fascia autograft group was 95 per cent. The tympanoplasty success rate in the Zenoderm xenograft group was only 40 per cent. All Zenoderm tympanoplasty failures were regrafted with temporalis fascia autograft. There was a 100 per cent success rate with this salvage surgery. In conclusion, we suggest that Zenoderm is not a suitable graft material for tympanoplasty.     

Effect of SC-41930, a potent selective leukotriene B4 receptor antagonist, in the guinea pig model of middle ear inflammation

Arachidonic acid metabolites such as prostaglandins and leukotrienes have been shown to play an important role in the pathogenesis of otitis media (OM). Among these mediators, leukotriene B4 (LTB4) is one of the most potent inducers of inflammatory processes. SC-41930 has been shown to be a specific LTB4 receptor antagonist both in vitro and in vivo. In this study, anti-inflammatory effects of SC-41930 were investigated in a guinea pig model of OM induced by middle ear (ME) inoculation of killed Staphylococcus aureus. Outcome of treatment was determined by measurement of myeloperoxidase activity in the samples of ME mucosa, evaluation of temporal bone histopathology, and presence of ME fluids. Myeloperoxidase activity in the SC-41930-treated group was found to be significantly lower than that in the control group. Histopathology of temporal bones indicated decreased inflammation in the treated group as compared to the controls. In addition, ME fluids were absent in four out of six treated animals. These results demonstrate that SC-41930 can produce significant anti-inflammatory effects in this model of OM.