Ralstonia pickettii-Induced Ataxia in Immunodeficient Mice

We report here the characterization of an asymmetric ataxia syndrome (head tilt and circling, with death in the most severe cases) demonstrated by profoundly immunodeficient mice housed at the Institut Curie SPF facility. The immune system of the affected mice had been genetically modified so that they were deficient in both B and T cells. Extensive bacteriologic, parasitic, serologic, and histopathologic analysis of the affected animals and their healthy controls led us to identify Ralstonia pickettii as the causative agent of the ataxic syndrome. The outbreak was managed through a test-and-cull process. Even though they also carried Ralstonia pickettii, immunocompetent mice that were kept in the same facility, did not show any of the signs that were expressed by their immunodeficient counterparts. This case highlights the difficulty of maintaining immunocompetent and immunodeficient mice in the same microbiologic unit and the importance of enlarging the spectrum of health monitoring to opportunistic agents when investigating clinical cases in populations of immunocompromised rodents.Ataxic mice occur occasionally in laboratory rodent colonies, and this clinical presentation is often due to otitis media. Numerous pathogens have been implicated in otitis media cases, including common pathogenic, opportunistic, and even commensal bacteria, such as Staphylococcus haemolyticus, Pasteurella pneumotropica, Corynebacterium spp., Mycoplasma pulmonis, Streptococcus pneumoniae, and Pseudomonas aeruginosa.^7,17 Although the syndrome has been reported to occur in immunocompetent rodent models, immunodeficient animals are more susceptible to bacterially induced otitis media.^2,9,14 For example, a deficiency in innate immunity due to a single amino-acid substitution in Toll-like receptor 4 (TLR4) makes the C3H/HeJ mouse a spontaneous model of chronic otitis media.^12,13 When ataxia is caused by bacterial otitis-induced peripheral vestibular syndrome, the etiologic agent should be identified so that the most appropriate management scheme can be adopted.     

Occurrence and Population Size of <Emphasis Type="Italic">Malassezia</Emphasis> spp. in the External Ear Canal of Dogs and Cats Both Healthy and with Otitis

Malassezia yeasts are commensal organisms of human and animal skin that occasionally act as pathogens; lipid-dependent species are associated with human skin disorders. The aim of this work was to evaluate the occurrence, risk factors and population size of different species of Malassezia in the external ear canal of dogs and cats with and without otitis externa. Between 2001 and 2003, 107 healthy animals (25 cats and 82 dogs) and 123 animals with chronic otitis exteirna (48 cats and 75 dogs) were clinically examined. Sterile cotton swabs were used to collect specimens from the external ear canal and culture tests and cytological examinations were performed to detect the presence and population size of Malassezia yeasts. Malassezia yeasts were isolated from 72.9% and 40% of the cats and from 57.3% and 28.0% of the dogs, with and without otitis externa, respectively. Malassezia was frequently isolated from animals under 5 years of age. The highest prevalence of positive samples was reported in winter for cats and in autumn for dogs. Dogs with pendulous ears showed a higher incidence of infection than dogs with erect ears. More Malassezia yeasts were recovered from animals with otitis (i.e. 59.6 colony forming units – CFUs – for cats and 66.0 CFUs for dogs) than healthy animals. Out of the 413 isolates obtained from animals with and without otitis, 403 (97.6%) were identified as M. pachydermatis and 10 (2.4%) as M. globosa. A statistical evaluation of the occurrence of Malassezia yeasts in dogs and cats revealed that predisposing factors for Malassezia infections are sampling period for cats, and type of ear for dogs. The largest population of Malassezia yeasts was detected in animals with otitis, suggesting a role in the occurrence of lesions.     

Twice-daily antibiotics in the treatment of acute otitis media: trimethoprim-sulfamethoxazole versus amoxicillin-clavulanate.

Twice-daily trimethoprim-sulfamethoxazole has been shown to be effective in the treatment of acute otitis media except that caused by group A beta-streptococci. Amoxicillin-clavulanate potassium is effective in vitro against all bacterial pathogens causing acute otitis media and has been reported to be effective when given twice daily for urinary tract infections, acute otitis media and respiratory tract infections. To determine whether the in-vitro efficacy of amoxicillin-clavulanate carries over clinically, we conducted a prospective randomized double-blind trial in 219 children presenting at a pediatric walk-in clinic. Diagnosis and follow-up assessments were made by means of examination of the tympanic membrane and acoustic otoscopy. Of the 219 children 202 (101 in either group) were assessed by a specially trained nurse at a follow-up visit 12 to 16 (mean 14) days after treatment was begun. Cure was defined as absence of symptoms and normal results of both visual inspection of the tympanic membrane and acoustic reflectometry; improvement was defined as absence of symptoms and either normal appearance of the tympanic membrane or normal results of acoustic reflectometry; treatment failure was defined as abnormal appearance of the tympanic membrane along with an acoustic reflectometry reading of 5 units or more. There were no differences in age (mean 60 months), sex or proportion of subjects with unilateral versus bilateral disease between the two groups. The combined rate of cure an improvement was significantly higher with trimethoprim-sulfamethoxazole (93%) than with amoxicillin-clavulanate (82%) (p = 0.03). The rate of compliance (more than 80% of the drug taken) did not differ significantly between the two groups. Gastrointestinal side effects were more common with amoxicillin-clavulanate (p less than 0.0001). Our results suggest that for acute otitis media twice-daily trimethoprim-sulfamethoxazole is more effective clinically and produces fewer side effects than twice-daily amoxicillin-clavulanate.     

Duration and recurrence of otitis media with effusion in children from birth to 3 years: prospective study using monthly otoscopy and tympanometry.

OBJECTIVE: To monitor the natural course of otitis media with effusion. DESIGN: Prospective, longitudinal assessment of the state of the middle ear by otoscopy and tympanometry at monthly intervals from birth to 3 years. SETTING: Domiciliary visits to family homes. SUBJECTS: 95 full term infants born between August 1991 and November 1993. MAIN OUTCOME MEASURES: Observed and simulated data (Monte Carlo) for the duration of single episodes of otitis media with effusion. RESULTS: 17 of the children had unilateral or bilateral otitis media with effusion for more than half of their first three years of life. Thirty three of the 95 children had tympanograms suggestive of otitis media with effusion at more than a third of observations; the remaining 62 had such tympanograms at less than a third of observations. The data of each group were described by a first order Markov model, yielding a mean duration of unilateral effusion episodes of 5-6 weeks in both groups; the mean duration of bilateral effusion was 6 and 10 weeks in the low and high incidence groups, respectively. However, the main difference between the groups was the time spent between episodes of effusion: effusion free periods were, on average, three times longer in the children who experienced less otitis media with effusion. CONCLUSION: Children who are susceptible to otitis media with effusion tend to have more separate episodes of effusion rather than an increased overall duration of episodes. Such children are primarily distinguished by the likelihood with which they acquire the disease than by their ability to recover from it.     

A survey of Pneumocystis carinii infection in research mouse colonies in Japan.

To determine the frequency of Pneumocystis carinii infection in mouse colonies maintained for biomedical research in medical colleges or medical faculties in universities in Japan, 409 nu/nu mice were sent to 43 animal facilities from a P. carinii-free colony. The animals were housed for 6 months in groups of 3 to 10 animals per room, and examined for the presence of parasites and infection. Colonies in 10 (24.4%) of 41 facilities were positive for the infection. Of 383 animals in 69 rooms, the organism was detected in 66 (17.2%) animals in 13 (18.8%) rooms. The difference in the proportion of rooms where mice were positive for P. carinii is clearly seen among these three groups; SPF mouse rooms (4 of 38 rooms, 10.5%), SPF mouse rooms with breeding units (5 of 25 rooms, 20.0%) and conventional mouse rooms (4 of 6 rooms, 66.7%). The survey indicates that strict housing arrangements and husbandry techniques are necessary to keep SPF mice free from P. carinii infection.     

Sulfisoxazole Chemoprophylaxis and Recurrent Otitis Media

Sulfisoxazole, 75 mg per kg per day, was administered for 13 weeks to all children with otitis media recurring at a rate of at least once every other month. The first 26 patients began prophylaxis during the months of January and February of 1979. To compare rates of otitis media with those in children not receiving concurrent prophylaxis during the same season, a matched control was randomly chosen as a child who began prophylaxis on the day nearest that when a study patient completed prophylaxis. The rates of otitis media during this same period were determined as the number of episodes per patient-month. Of the 26 treated patients, 11 had 16 episodes of otitis media in 72 patient-months (0.22 episodes per patient-month), in contrast to the 26 untreated patients who had 63 episodes in the same period (0.88 episodes per patient-month). This 75% reduction in incidence was statistically significant by X² analysis (P<.005). The two groups of children were comparable in age, sex, nursery school attendance, family history of allergy and number of episodes in the three months preceding chemoprophylaxis. These findings support the short-term chemoprophylactic use of sulfisoxazole for recurrent otitis media.     

腺样体手术治疗儿童分泌性中耳炎的临床疗效观察

目的:观察腺样体手术治疗儿童分泌性中耳炎的临床效果。方法:选择分泌性中耳炎合并腺样体肥大患儿80例(160耳),将其随机分为手术组和对照组,每组40例,手术组患儿给予腺样体消融手术治疗,而对照组患儿进行保守治疗,观察和比较两组治疗1个月后的临床疗效。结果:治疗1个月后,手术组治愈72耳,好转6耳,治疗总有效率为97.5%,而对照组治愈8耳,好转20耳,治疗总有效率为35%,较手术组显著降低(P0.05)。结论:腺样体切除是治疗分泌性中耳炎的有效途径,治疗中应尽可能避免并发症的发生,恢复和保护咽鼓管的生理功能。     

Effects of Metabolic Cage Housing on Rat Behavior and Performance in the Social Interaction Test

Although the metabolic cage is commonly used for housing nonhuman animals in the laboratory, it has been recognized as constituting a unique stressor. Such an environment would be expected to affect behavioral change in animals housed therein. However, few studies have specifically addressed the nature or magnitude of this change. The current study sought to characterize the behavioral time budget of rats in metabolic cage housing in comparison to that of individually housed animals in standard open-top cages. Rats in metabolic cages spent less time moving, manipulating enrichment, and carrying out rearing behaviors, and there was a corresponding shift toward inactivity. In an applied Social Interaction Test, behavioral scoring implied that metabolic cage housing had an anxiogenic effect. In conclusion, metabolic cage housing produces measurable effects on spontaneous and evoked behavior in rats in the laboratory. These behavioral changes may lead to a negative emotional state in these animals, which could have negative welfare consequences. Further research is needed to quantify the existence and magnitude of such an effect on rat well being.     

腺样体手术治疗儿童分泌性中耳炎的临床疗效观察

目的：观察腺样体手术治疗儿童分泌性中耳炎的临床效果。方法：选择分泌性中耳炎合并腺样体肥大患儿80例（160耳）,将其随机分为手术组和对照组,每组40例,手术组患儿给予腺样体消融手术治疗,而对照组患儿进行保守治疗,观察和比较两组治疗1个月后的临床疗效。结果：治疗1个月后,手术组治愈72耳,好转6耳,治疗总有效率为97．5％,而对照组治愈8耳,好转20耳,治疗总有效率为35％,较手术组显著降低（P〈0．05）。结论：腺样体切除是治疗分泌性中耳炎的有效途径,治疗中应尽可能避免并发症的发生,恢复和保护咽鼓管的生理功能。     

Policies on antibiotics of south east London general practitioners for managing acute otitis media in children.

Questionnaires on antibiotic treatment of acute otitis media in children were sent to the general practitioners who make regular referrals to clinics in the King''s College Hospital group. The most popular first choice of drug was amoxycillin (44%), but 37% of general practitioners said that they often used oral phenoxymethylpenicillin. This drug has relatively low activity against Haemophilus influenzae and many strains of Staphylococcus aureus. It is poorly absorbed from the stomach, does not penetrate the middle ear well, and its use may be one factor in the development of chronic middle ear effusions after acute otitis media. Sixty two per cent of the doctors who replied never treated acute otitis media with intramuscular antibiotics, but 57% used oral loading doses. Ninety seven per cent never treated their patients without antibiotics.     

A novel method for activity monitoring in small non-human primates

Patterns of spontaneous activity are valuable reflections of well-being in animals and humans and, because of this, investigations have frequently incorporated some form of activity monitoring into their studies. It is widely believed that activity monitoring, alongside assessments of general behaviour, should be included in initial CNS safety pharmacology screening. As the number of marmoset studies having actimetry as their focus, or as an adjunct, is increasing, we wished to evaluate an alternative approach to those commonly used. The method is based on miniaturized accelerometer technologies, currently used for human activity monitoring.Actiwatch-Minis were used to monitor the activity of two groups of differently housed marmosets for 14 consecutive days. Group A consisted of four mixed-sex pairs of animals and group B comprised eight group-housed males. Activity profiles were generated for weekday and weekend periods. The devices captured quantifiable data which showed differences in total activity between the two differently housed groups and revealed intragroup variations in the temporal spread of activity between weekdays and weekends. The Actiwatch-Mini has been shown to generate retrospective, data-logged activity counts recorded from multiple animals in a single arena by means of non-invasive monitoring.     

Social interaction in nonhuman primates: an underlying theme for primate research.

Social living is assumed to be a critical feature of nonhuman primate existence inasmuch as most primate species live in social groups in nature. Recent USDA legislation emphasizes the importance of social contact in promoting psychological well-being and recommends that laboratory primates be housed with companions when consistent with research protocols. Our goals were to examine the link between social housing and psychological well-being and to explore the idea that research may be compromised when primates are studied in environments that vary too greatly from their natural ecological setting (individual cage housing versus group housing). Three general points emerge from these examinations. First, providing companionship may be a very potent way in which to promote psychological well-being in nonhuman primates; however, social living is not synonymous with well-being. The extent to which social housing promotes psychological well-being can vary across species and among individual members of the same species (for example, high- and low-ranking monkeys). Secondly, housing conditions can affect research outcomes in that group-housed animals may differ from individually housed animals in response to some manipulation. Social interaction may be a significant variable in regulating the biobehavioral responses of nonhuman primates to experimental manipulations. Finally, a larger number of socially housed subjects than individually housed subjects may be necessary for some biomedical research projects to yield adequate data analysis. Thus, social living has significant benefits and some potential costs not only for the animals themselves, but for the research enterprise.     

Spontaneous "regression" of enhanced immune function in a photoperiodic rodent Peromyscus maniculatus.

Short days inhibit reproduction and enhance immune function in deer mice (Peromyscus maniculatus). Their reproductive inhibition is sustained by an endogenous timing mechanism: after ca. 20 weeks in short days, reproductive photorefractoriness develops, followed by spontaneous recrudescence of the reproductive system. It is unknown whether analogous seasonal timing mechanisms regulate their immune function or whether enhanced immune function is sustained indefinitely under short days. In order to test this hypothesis, we housed adult male deer mice under long (16 h light day(-1)) or short (8 h light day(-1)) day conditions for 32 weeks or under long day conditions for 20 weeks followed by 12 weeks of short days. Mice under the long day conditions remained photostimulated over the 32 weeks, whereas mice housed under the short day conditions exhibited gonadal regression followed by photorefractoriness and spontaneous recrudescence. Mice transferred to short days at week 20 were reproductively photoregressed at week 32. Total splenocytes, relative splenic mass and mitogen-activated splenocyte proliferation were greater in those mice transferred to short days at week 20 than in those mice housed under either long or short day conditions for 32 consecutive weeks, and immune function in mice exposed to short days for 32 weeks was comparable with that of long day animals. These data suggest that short day enhancement of immune function is not indefinite. With prolonged (< or = 32 weeks) exposure to short days, several measures of immune function exhibit "spontaneous" regression, restoring long day-like immunocompetence. The results suggest that formal similarities and, possibly, common substrates exist among the photoperiodic timekeeping mechanisms that regulate seasonal transitions in reproductive and immune function.     

Etiology and rational therapy of severe otitis media purulenta acuta in children]

Etiology and antibiotic susceptibility of the pathogens of otitis media purulenta acuta in children was studied within 2000-2005. A total of 161 children at the age of 1 to 14 years were examined. The middle ear discharge collected during paracentosis (79.5%) or spontaneous perforation of the tympanic membrane (20.5%) was used in the bacteriological tests. The microflora growth in the culture was detected in 80% of the cases. The leading pathogen was Streptococcus pyogenes (47.5%), the part of Streptococcus pneumoniae amounted to 36.6% of all the etiologically significant microflora, the part of Staphylococcus aureus amounted to 6.9% and that of Haemophilus influenzae amounted to 4.0%. The part of the associations of 2 microorganisms equaled 5.0%. The species composion of the pathogens differed from that described in the literature. The isolates of S. pneumoniae and S. pyogenes were characterized by low resistance to macrolides (4.0-6.3%). As for the S. pneumoniae isolates, 97.3% of them was susceptible to penicillin. The results of the etiology study and the pathogen antibiotic susceptibility showed that the drugs of choice for the empirical antibacterial therapy of otitis media purulenta acuta in children should be amoxicillin and 1st generation cepholosporins. When the antibacterial therapy within the first 3 days fails, it is advisable to use protected aminopenicillins or 2nd generation cephalosporins. In case of the drug intolerance, macrolide antibiotics should be used.     

改良乳突根治术联合后上壁重建对上鼓室胆脂瘤型中耳炎患者听力改善及复发率的影响

摘要 目的：探讨改良乳突根治术联合后上壁重建对上鼓室胆脂瘤型中耳炎患者听力改善及复发率的影响。方法：选取本院2015年5月-2020年10月收治的62例上鼓室胆脂瘤型中耳炎患者作为研究对象,随机将其分为改良组（n=31）和对照组（n=31）。改良组采用改良乳突根治术联合后上壁重建进行治疗,对照组采用乳突根治术进行治疗,对比两组患者手术前后听力情况、术后干耳所需时间等指标。结果：治疗前两组患者的气骨导差、气导听阀对比无明显差异（P>0.05）,治疗后均降低,并且改良组低于对照组（P＜0.05）;改良组患者术后并发症发生率较对照组低（P＜0.05）;改良组患者的术后2周、4周、8周干耳率较对照组高（P＜0.05）,术后干耳所需时间低于对照组（P＜0.05）;改良组治疗总有效率较对照组高（P＜0.05）。结论：将改良乳突根治术联合后上壁重建应用于上鼓室胆脂瘤型中耳炎患者当中,可提高患者听力,降低并发症,还可提高患者干耳率,缩短干耳时间,降低复发率,提高临床疗效,本研究值得临床借鉴。     

Are antibiotics indicated as initial treatment for children with acute otitis media? A meta-analysis.

OBJECTIVE: To determine the effect of antibiotic treatment for acute otitis media in children. DESIGN: Systematic search of the medical literature to identify studies that used antibiotics in randomised controlled trials to treat acute otitis media. Studies were examined blind, and the results of those of satisfactory quality of methodology were pooled. SUBJECTS: Six studies of children aged 7 months to 15 years. MAIN OUTCOME MEASURES: Pain, deafness, and other symptoms related to acute otitis media or antibiotic treatment. RESULTS: 60% of placebo treated children were pain free within 24 hours of presentation, and antibiotics did not influence this. However, at 2-7 days after presentation, by which time only 14% of children in control groups still had pain, early use of antibiotics reduced the risk of pain by 41% (95% confidence interval 14% to 60%). Antibiotics reduced contralateral acute otitis media by 43% (9% to 64%). They seemed to have no influence on subsequent attacks of otitis media or deafness at one month, although there was a trend for improvement of deafness at three months. Antibiotics were associated with a near doubling of the risk of vomiting, diarrhoea, or rashes (odds ratio 1.97 (1.19 to 3.25)). CONCLUSIONS: Early use of antibiotics provides only modest benefit for acute otitis media: to prevent one child from experiencing pain by 2-7 days after presentation, 17 children must be treated with antibiotics early.     

Influence of Pneumococcal Conjugate Vaccine on Acute Otitis Media with Severe Middle Ear Inflammation: A Retrospective Multicenter Study

The Japanese guidelines for acute otitis media in children recommend classifying acute otitis media by age, manifestations and local findings, and also recommend myringotomy for moderate-grade cases with severe local findings, severe-grade cases, and treatment-resistant cases. The heptavalent pneumococcal conjugate vaccine was released in Japan in February 2010. In Hiroshima City, public funding allowing free inoculation with this vaccine was initiated from January 2011, and the number of vaccinated individuals has since increased dramatically. This study investigated changes in the number of myringotomies performed to treat acute otitis media during the 5-year period from January 2008 to December 2012 at two hospitals and five clinics in the Asa Area of Hiroshima City, Japan. A total of 3,165 myringotomies for acute otitis media were performed. The rate of procedures per child-year performed in <5-year-old children decreased by 29.1% in 2011 and by 25.2% in 2012 compared to the mean rate performed in the 3 years prior to the introduction of public funding. A total of 895 myringotomies were performed for 1-year-old infants. The rate of myringotomies per child-year performed for acute otitis media in 1-year-old infants decreased significantly in the 2 years after the introduction of public funding for heptavalent pneumococcal conjugate vaccine compared to all years before introduction (p<0.000001). Our results suggest a benefit of heptavalent pneumococcal conjugate vaccine for acute otitis media in reducing the financial burden of myringotomy. In addition, this vaccine may help prevent acute otitis media with severe middle ear inflammation in 1-year-old infants.     

Ringtail in the pouched mouse (Saccostomus campestris)

Laboratory colonies of the pouched mouse (Saccostomus campestris) were housed in solid bottom cages and fed a varied diet containing excess fatty acids. Ringtail was only initiated in animals of all ages, from populations originating from different areas of South Africa, when the relative humidity fell below 30%. The incidence of ringtail was curtailed by maintaining relative humidity above 45% in animal houses.     

Dr. Mary Fanning: caring for AIDS patients at Toronto General.

Although amoxicillin has long been the preferred drug for treatment of acute otitis media, resistant strains of two relatively common causal organisms have emerged, prompting a search for other antibiotics. We performed a randomized double-blind trial comparing amoxicillin and trimethoprim-sulfamethoxazole in 221 children in whom acute otitis media was diagnosed in an outpatient setting. Diagnosis was on the basis of symptoms, otoscopic examination and acoustic reflectometry. No culture specimens were taken. A research nurse, using the same methods, evaluated patients in a follow-up home visit at around 14 days and measured compliance by examination of the medicine bottle. Equal proportions of children in the two groups were cured or improved (88% and 87%). Therapeutic efficacy was related to compliance in both groups, and there were few side effects in either group. This study had statistical power of 80% to detect a difference of 15%. We conclude that trimethoprim-sulfamethoxazole can be considered a first-line antibiotic in the treatment of acute otitis media.