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Peripheral facial palsy is a common clinical symptom and is most often caused by Bell's palsy. The pathogenesis is largely unknown, but inflammation of the facial nerve, possibly after a viral infection, may play a role. Bell's palsy has a monophasic course with usually - but not always - a good recovery. Even though Bell's palsy exhibits clear clinical features, in clinical practice diagnosis and choice of treatment remain difficult and other causes of an isolated facial palsy may easily be overlooked.

Purpose: Differences in the definition and classification of cholesteatoma hinders comparing of surgical outcomes of cholesteatoma. Uniform registration is necessary to allow investigators to share and compare their findings. For many years surgical cholesteatoma procedures were divided into two main groups: canal wall up mastoidectomy (CWU) and canal wall down mastoidectomy (CWD). Recently, mastoid obliteration can be added to both procedures. Because of great variation within these main groups, the International Otology Outcome Group (IOOG) proposed the new SAMEO-ATO classification system to categorize tympanomastoid operations. The aim of our study was to correlate the mastoid bone extirpation (M-stage) with the contemporary (CWU, CWD with or without obliteration) system., Methods: Demographic characteristics and type of performed surgery were registered for 135 cholesteatoma patients from sixteen hospitals, both secondary and tertiary care institutions, across the Netherlands. In addition, the surgical reports were collected, retrospectively classified according to the contemporary system and the new system and compared. Correlations of the outcomes were calculated., Results: In total, there were 112 CWU and 14 CWD (both with or without obliteration) suitable for correlation analysis. Z test for correlation between the M-stage and CWU procedure was significant for M1a and M1b procedure and significant for M2c with the CWD procedure., Conclusion: The newly proposed SAMEO-ATO classification seems to be more detailed in the registration of surgical procedures than surgeons currently are used to. All M-stages of the SAMEO-ATO system are correlating well to the standard CWU and CWD except one 'in between' M-stage.

Background and Purpose: Ménière disease is characterized by endolymphatic hydrops, whereas perilymphatic enhancement on MR imaging has been suggested to be of additional value in diagnosing Ménière disease. This study evaluates the presence of endolymphatic hydrops and perilymphatic enhancement in patients with Ménière disease and with other vertigo-associated inner ear pathology., Materials and Methods: A 3D-FLAIR sequence 4 hours after intravenous gadolinium injection was performed to visualize the endolymph and perilymph in 220 patients suspected of having Ménière disease. Patients' ears were retrospectively categorized as having Ménière disease (probable or definite) or other vertigo-associated inner ear pathology not attributable to Ménière disease. Endolymphatic hydrops was evaluated using a visual classification system, and perilymphatic enhancement was scored both visually and quantitatively., Results: Endolymphatic hydrops was present in 137 (91.9%) of the definite Ménière disease ears and in 9 (7.0%) of the ears with other vertigo-associated inner ear pathology ( P < .001). The combination of endolymphatic hydrops and visually increased perilymphatic enhancement was present in 122 (81.9%) definite Ménière disease ears compared with 4 (3.1%) ears with other vertigo-associated inner ear pathology ( P < .001). This combination increases the positive predictive value from 0.94 for endolymphatic hydrops and 0.91 for perilymphatic enhancement to 0.97. The addition of measured perilymphatic enhancement leads to a moderate decrease in sensitivity from 0.92 for endolymphatic hydrops to 0.86., Conclusions: The combination of perilymphatic enhancement and endolymphatic hydrops in patients suspected of having Ménière disease increases the positive predictive value in the diagnosis of definite Ménière disease., (© 2020 by American Journal of Neuroradiology.)

Auditory agnosia for environmental sounds (AES) is an example of central auditory dysfunction. It is presumed to be independent of language deficits and in presence of normal hearing. We undertook a detailed neuropsychological assessment including environmental sound naming and recognition in 34 clinically mild Alzheimer's disease (AD) patients and 29 age-matched healthy control subjects. In patients with AD, audiometry was performed to assess the impact on test performance, and in normal controls the Hearing Handicap Inventory for the Elderly - Screening Version to exclude more than mild hearing loss. We adapted a validated environmental sound battery and found near perfect scores in controls. We found that environmental sound agnosia is common in mild AD. We found a statistically significant difference in mean pure tone audiometry in the best ear between patients with and those patients without naming deficits of 11.3 dB (p = 0.010) and of 14.7 dB (p = 0.000) between those with and without recognition deficits. Statistical significance remained after correcting for age, aphasia, Mini-Mental State Examination score, and working memory. Slight and moderate peripheral hearing loss increases the odds ratio of recognition deficits by 13.75 (confidence interval 2.3-81.5) compared to normal hearing patients. We did not find evidence for different forms of AES. This work suggests that an interaction between peripheral hearing loss and AD pathology produces problems with environmental sound recognition. It confirms that the relationship between hearing and dementia is complex but also suggests that interventions to prevent and treat hearing loss could have an effect on AD in its clinical expression.

Schistosomiasis is a parasitic infection highly prevalent in sub-Saharan Africa, and a significant cause of morbidity; it is a priority for vaccine development. A controlled human infection model for Schistosoma mansoni (CHI-S) with potential to accelerate vaccine development has been developed among naïve volunteers in the Netherlands. Because responses both to infections and candidate vaccines are likely to differ between endemic and non-endemic settings, we propose to establish a CHI-S in Uganda where Schistosoma mansoni is endemic. As part of a "road-map" to this goal, we have undertaken a risk assessment. We identified risks related to importing of laboratory vector snails and schistosome strains from the Netherlands to Uganda; exposure to natural infection in endemic settings concurrently with CHI-S studies, and unfamiliarity of the community with the nature, risks and rationale for CHI. Mitigating strategies are proposed. With careful implementation of the latter, we believe that CHI-S can be implemented safely in Uganda. Our reflections are presented here to promote feedback and discussion., Competing Interests: Competing interests: The authors have declared no personal financial competing interests. However, we are working collaboratively to develop the CHI-S for implementation in Uganda, and therefore have research goals with potential to influence our approach to this risk assessment. This is, in part, our motivation for publishing it on an open peer review platform.

Objective: To compare the diagnostic work-up and treatment strategy of Bell's palsy by: general practitioners (GPs); ear, nose and throat (ENT) specialists; and neurologists in the Netherlands., Design: Cross-sectional survey., Method: GPs, ENT specialists and neurologists were asked to participate in an online survey on the diagnosis and treatment of Bell's palsy. Results per specialty were analysed using descriptive statistics and chi-squared test., Results: A total of 415 clinicians participated, including 149 GPs, 123 ENT specialists, and 143 neurologists. The answers from the three disciplines showed significant differences concerning history taking, physical examination, alarm symptoms, treatment strategy and follow-up. ENT specialists more frequently asked about hearing loss (90%), whereas neurologists enquired about weakness in arms and legs (62%). GPs less often ask about tick bites than clinicians in ENT and neurology, respectively (36% vs. 89% and 71%). Neurologists rarely performed otoscopy (21%), but more frequently tested eye movements (78%) than GPs (33%) and ENT specialists (20%). Compared to GPs and neurologist, ENT specialists more frequently reported the supplementation of Prednisone treatment with antiviral agents (45% vs. 9% and 6 % resp.). Furthermore, the time interval to the follow-up visit varied strongly between clinicians, ranging between a few days to six weeks after the first clinic visit., Conclusion: This study shows that the diagnostic work-up and treatment strategy for Bell's palsy in the Netherlands is highly dependent on the clinician's specialty. Despite the fact that equivalent guidelines are in place, GPs, ENT specialists and neurologists gave different answers to questions concerning diagnostics and treatment. This finding suggests that more attention should be paid to the implementation of and adherence to the multidisciplinary guideline for Bell's palsy.

Background: Myringoplasty is a common procedure in otorhinolaryngology. Many techniques with different complications and outcomes have been described, one of which is hyaluronic acid fat graft myringoplasty (HAFGM). This technique, as proposed by Saliba, uses fat tissue and hyaluronic acid discs. The technique is relatively fast with a high success rate and low complications. However, what outcomes can be expected when performed by other surgeons? In this paper, we report on the technique's success in our own hands., Materials and Methods: Based on Saliba's protocol, we performed 86 HAFGMs by a transcanal approach between 2012 and August 2014. However, our 70% success rate was significantly different from Saliba's 92% (p value 2.8e - 05). We visited Saliba's clinic in order to identify critical differences between our approaches. We adapted the differences we found in our protocol and analysed another 50 HAFGMs performed afterwards, between October 2014 and December 2015., Results: The success rate increased to 86-89%, this percentage is not different compared to Saliba's results (p value .25 and .54)., Conclusion: HAFGM is a reproducible technique in the hands of other surgeons, but critical following of the surgical protocol is important.

Objective: In this study a type of partial tonsil surgery, CO2-laser tonsillotomy, was compared to regular tonsillectomy. The effectiveness and post-operative recovery rate of both interventions in adult patients was assessed by using a questionnaire., Study Design: Prospective follow-up non-randomized cohort study., Method: One hundred and seven adults were included; 46 tonsillectomies and 61 tonsillotomies were performed. Patients in the tonsillectomy group underwent general anaesthesia, while tonsillotomy was performed in an ambulatory setting with local anaesthesia. Post-operative questionnaires were administered by mail after 2 weeks, 6 months, and 1 year to assess recovery rate and symptom recurrence., Results: In total, 72.5% of patients were cured from their initial symptoms after tonsillotomy. Three patients (7.5%) required re-surgery for their initial complaints. After tonsillectomy, 97.2% of patients were cured. Both groups showed equally high satisfaction scores after treatment. Post-operative evaluation after 2 weeks showed a mean pain-intensity score of 5.4 (Visual Analogue Scale 0-10) after tonsillotomy and a mean pain-intensity score of 7.7 after tonsillectomy. The post-operative use of analgesics was twice as long in the tonsillectomy group compared to the tonsillotomy group and the tonsillectomy group required twice as many days for full recovery. After tonsillectomy a higher rate of major post-operative haemorrhage was seen., Conclusion: CO2-laser tonsillotomy is associated with a shorter and less painful recovery period. Both surgical methods are equal in terms of long-term satisfaction, although tonsillotomy comes with a higher recurrence rate of mild symptoms. A strict pre-operative patient selection for CO2-laser tonsillotomy is necessary.

Objective/purpose: Febrile urinary tract infection (UTI) is a common bacterial disease that may lead to substantial morbidity and mortality especially among the elderly. Little is known about biomarkers that predict a complicated course. Our aim was to determine the role of certain urinary cytokines or antimicrobial proteins, plasma vitamin D level, and genetic variation in host defense of febrile UTI and its relation with bacteremia., Methods: A case-control study. Out of a cohort of consecutive adults with febrile UTI (n = 787) included in a multi-center observational cohort study, 46 cases with bacteremic E.coli UTI and 45 cases with non-bacteremic E.coli UTI were randomly selected and compared to 46 controls. Urinary IL-6, IL-8, LL37, β-defensin 2 and uromodulin as well as plasma 25-hydroxyvitamin D were measured. In 440 controls and 707 UTI patients polymorphisms were genotyped in the genes CXCR1, DEFA4, DEFB1, IL6, IL8, MYD88, UMOD, TIRAP, TLR1, TLR2, TLR5 and TNF., Results: IL-6, IL-8, and LL37 are different between controls and UTI patients, although these proteins do not distinguish between patients with and without bacteremia. While uromodulin did not differ between groups, inability to produce uromodulin is more common in patients with bacteremia. Most participants in the study, including the controls, had insufficient vitamin D and, at least in winter, UTI patients have lower vitamin D than controls. Associations were found between the CC genotype of IL6 SNP rs1800795 and occurrence of bacteremia and between TLR5 SNP rs5744168 and protection from UTI. The rare GG genotype of IL6 SNP rs1800795 was associated with higher β-defensin 2 production., Conclusion: Although no biomarker was able to distinguish between UTI with or without bacteremia, two risk factors for bacteremia were identified. These were inability to produce uromodulin and an IL6 rs1800795 genotype.

A 37-year-old male cocaine user presented with continual, sanguinolent nasal obstruction and persistant pain following a nasal operation one year ago. Examination showed crustae, granulations and exposed septal cartilage in the right nasal passage in addition to a considerable septal deviation to the left. No other physical abnormalities were found. A biopsy of the nasal mucosa showed acute necrotic inflammation. The serological examination revealed markedly elevated anti-neutrophil cytoplasmic antibodies (ANCA) titres with positive reactions against proteinase-3, indicating Wegener's disease. Additional testing also showed a positive ANCA reaction for human neutrophil elastase, which made cocaine use a more plausible cause for the nasal abnormalities than Wegener's disease. Treatment consisted of nasal flushing with saline and, for a short period, a nasal tampon with hydrocortisone-oxytetracycline-polymyxin B ointment. However, the patient did, ultimately, develop a septal perforation. Cocaine-induced nasal abnormalities can imitate symptoms that may fit Wegener's disease, including relevant serological ANCA findings.

Objectives: Insertion of ventilation tubes in children with otitis media with effusion (OME) is an accepted and common treatment procedure. The majority of patients require general anesthesia. Although laser myringotomy can be performed in local anesthesia, evidence is lacking that this treatment modality is an alternative for tubes, and outcome predictors for laser myringotomy are not available., Study Design: Prospective randomized trial., Methods: We screened 1,403 children with chronic OME that were indicated for placement of ventilation tubes. In the eligible patients, we performed laser myringotomy in one ear and placed a tube in the other ear, both within the same patient. Follow-up was scheduled each month for 6 months. Success was defined as absence of effusion or aural discharge. A logistic regression model was used with success of the therapy as binary outcome. This model was based on base-line variables, asked for in a parent's questionnaire., Results: Two hundred eight children received the allocated intervention, and no complications occurred. The mean closure time of the laser perforation was 2.4 weeks, and the mean patency time of the ventilation tube was 4.0 months. The mean success rate was 40% for laser and 78% for tubes. Ten known variables were found to predict middle ear status after therapy., Conclusion: Laser myringotomy is a safe but less-effective procedure than insertion of a ventilation tube in the treatment of chronic OME. The prognostic model enables the otolaryngologist to choose the surgical treatment for the child that benefits most: laser myringotomy or ventilation tube.

Background: Within hypoxic tumor regions anaerobic dissimilation of glucose is the sole source of energy generation. It yields only 5% of the ATP that is normally gained by means of oxidative glucose catabolism. The increased need for glucose may aggravate cancer cachexia. We investigated the impact of recombinant human erythropoietin (RhEPO) and increased inspiratory oxygen concentrations on weight loss in tumor-bearing mice., Methods: Fragments of the murine C26-B adenocarcinoma were implanted in 60 BALB/c-mice. The mice were divided into four groups and assigned to: (A) no treatment; (B) RhEPO- administration (25 IU daily from day 1-11, three times per week from day 12); (C) RhEPO and 25% oxygen; and (D) RhEPO and 35% oxygen. Three control groups of four healthy mice each received the same treatment as groups A, B, and D, respectively. Hematocrit and hemoglobin levels, tumor volume, and body weight were monitored. At day 17 the experiment was terminated and the serum lactate concentration was measured. The tumors were excised and weighed and, for each mouse, the percentage weight loss was calculated. The impact of tumor weight and the treatments on lactate concentration and weight loss was evaluated., Results: Significant positive correlations were found between tumor weight and lactate concentration and between tumor weight and percentage weight loss. In the mice with the largest tumors, RhEPO displayed a significant weight loss-reducing effect, and a significant negative correlation was found between hemoglobin concentration and weight loss. An oxygen-rich environment did not appear to influence weight loss., Conclusion: Anaerobic glycolysis in a growing C26-B tumor is related to weight loss. RhEPO administration results in a reduction of the percentage weight loss; this effect is probably mediated by an increased hemoglobin concentration.

Background/purpose: The aim of this study was to add to the experience of slide tracheoplasty in infants with congenital tracheal stenosis (CTS), to review the recent literature on this subject, and to evaluate the diagnostic workup in infants with CTS., Methods: A retrospective review of 3 infants with CTS treated with slide tracheoplasty was conducted at our institution. They all underwent bronchoscopy, tracheobronchography, and echocardiography. Therapy consisted of slide tracheoplasty and simultaneous correction of associated vascular malformations., Results: A pulmonary artery sling was missed initially on esophagography in 2 patients. Stridor became worse in 2 patients after tracheobronchography. After surgical therapy, 2 patients survived and were discharged 12 days after surgery. Both are without symptoms at follow-up of 12 and 20 months. One patient had inoperable restenosis and died 27 days after the operation., Conclusions: Esophagography is not a reliable tool to depict associated vascular anomalies for patients with CTS. According to the literature, computer tomography has become more reliable to depict the tracheobronchial tree and is useful to elucidate associated vascular anomalies as well. Compared with other surgical techniques for infants with CTS reported in the literature, slide tracheoplasty has fewer postoperative complications and comparable survival rates.

In a cross-over trial, five healthy dogs were fed a dry food without or with 1% (w/w) oligofructose to assess any oligofructose-induced effects on the faecal bacterial profile, nitrogen excretion and mineral absorption. The diets were given for a period of 3 weeks. Oligofructose feeding significantly raised the number of Bifidobacteria, Streptococci and Clostridia in faeces. The numbers of faecal anaerobic and aerobic bacteria were raised after ingestion of oligofructose. The faecal pH was unchanged. There was no effect of oligofructose feeding on the route of nitrogen excretion which was associated with a lack of effect on faecal ammonium and urinary urea excretion. It is suggested that the absence or presence of an effect of oligofructose on urinary and faecal nitrogen excretion depends on the background composition of the diet, in particular the content of non-digestible, fermentable carbohydrates. In the diets used, the content of non-digestible, fermentable carbohydrates was not measured. Both apparent magnesium and calcium absorption were significantly raised by oligofructose feeding, but phosphorus absorption was unaffected. The data presented may contribute to the qualification of the use of oligofructose in dog foods.

This report describes the preparation of an immunotoxin-combination, consisting of an anti-CD3 and anti-CD7 monoclonal antibody (MoAb) both conjugated to the A-chain of plant toxin ricin, for the experimental treatment of graft-versus-host disease. MoAbs and toxin were conjugated by conventional biochemical and chromatographic techniques. Raw materials, intermediate and final products were evaluated in accordance with the relevant 'points to consider' of the FDA. Yields, purity and sterility of the two final products were all satisfactory. Preservation of MoAb-affinity and toxin-activity were confirmed in biological assays. The LD50, 25-45 mg immunotoxin-combination/kg mouse, equalled that of similar immunotoxins already in clinical use. Because in vitro cross-reactivity screening revealed an unexpected binding of the CD3-MoAb to the esophagus epithelium, human doses of immunotoxin-combination were administered to two cynomolgus monkeys. Clinically relevant serum concentrations were obtained without irreversible toxicities occurring. The T(1/2) varied between approximately 6 and 9 h and the C(max) ranged from 1.8 to 3.9 microg/ml. The main side effect was a transient rise of serum creatine kinase. Importantly, neither damage nor binding of the CD3-immunotoxin to the monkey esophagus epithelium could be demonstrated. It was concluded that sufficient material of proper quality and with an acceptable toxicity profile was produced, warranting the evaluation in a clinical pilot-study.

Objective: To evaluate the effect of claudication on nerve function in patients with unilateral peripheral arterial disease., Design: Prospective study., Setting: District hospital, The Netherlands., Subjects: 11 Patients with unilateral intermittent claudication (diagnosed from history and ankle-brachial blood pressure index) underwent electrophysiological studies of both legs, including nerve conduction velocities, motor unit action potentials, H-reflex measurements, and muscle strength testing. The asymptomatic leg was used as the control in each case., Results: Six patients had neuropathy in both the claudicating and the control leg. Three other patients had neuropathy in the claudicating leg only, which consisted mainly of disorders of nerve conduction including the H-reflex. There was no clear difference between muscle strength in the symptomatic and control legs, possibly because more than half the patients studied, had neuropathy in both legs., Conclusions: Neuropathy is common at an early stage of arterial disease and could be one of the factors leading to impaired muscle function in such patients.

The formation of Cholesteatoma is often accompanied by infection, and is very likely to be influenced by inflammatory mediators. Endotoxin, a strong inflammatory mediator, may play an important role in cholesteatoma pathogenesis. It has been demonstrated in middle ear effusions, and it causes marked reactions in middle ear epithelium and epidermis, both in vivo and in vitro. The effect of endotoxin on a simulation of the advancing front of cholesteatoma was investigated in this study. We developed a co-culture model composed of a simultaneous culture of rat middle ear mucosa and rat meatal epidermis in one culture dish, to which endotoxin was added. During the culture period the addition of endotoxin to the co-culture delayed take-over of the meatal epidermis by the middle ear mucosa, in comparison with control cultures. Morphological changes included the clustering of microvilli in co-cultures exposed to endotoxin. Although these results are preliminary, they suggest that endotoxin disturbs the normal healing process of the middle ear cavity.

In the covalent binding of nitroarenes to macromolecules, nitroreduction is an important step. The intestinal microflora represents an enormous potential of bacterial nitroreductase activity. As a consequence, the in vivo nitroreduction of orally administered nitroarenes is primarily located in the intestine. In this study, we have investigated the nitroreduction of 2-nitrofluorene (2-NF) by a human microflora in female Wistar rats. Germ-free (GF) rats were equipped with a bacterial flora derived from human feces. Nontreated GF rats and GF animals equipped with a conventional rat flora were used as controls. The composition of the human and the conventional microflora isolated from the rats were consistent with the microflora of the administered feces. In the rats receiving only sunflower seed oil, no adducts were detected. The animals equipped with a human or rat microflora that received 2-aminofluorene (2-AF) formed 2-AF hemoglobin (Hb)-adducts at average levels (mean +/- SEM) of 5.3 +/- 0.3 and 6.7 +/- 0.7 mumole/g Hb, respectively. After 2-NF administration, the adduct levels were 0.022 +/- 0.003 and 0.043 +/- 0.010 mumole/g Hb, respectively. In the GF rats, an adduct level of 0.57 +/- 0.09 was determined after 2-AF administration and no adducts were detected after 2-NF administration. The results show that nitroreduction by an acquired human intestinal microflora and subsequent adduct formation can be studied in the rat in vivo.

The role of the intestinal microflora in the metabolic activation of nitroarenes and arylamines was studied in female Wistar rats that received a dose of 1 mmol/kg 2-aminofluorene (2-AF) in sunflower oil by gavage. Another group received the same dose of 2-nitrofluorene (2-NF). A third group of animals was used as controls. Germfree (GF) rats, GF rats with a rat microflora (RM) and GF rats with a human microflora (HM) were treated. After treatment with 2-AF significant differences were observed in the formation of haemoglobin (Hb) adducts and DNA adducts. The 2-AF-Hb adduct level (mean +/- SD) observed in GF rats (0.57 +/- 0.13 mumol/g Hb) was considerably lower than that observed in RM rats (5.1 +/- 0.6) and in HM rats (6.2 +/- 1.3). DNA adduct levels showed the opposite pattern: levels of adducts co-migrating with deoxyguanosin-8-yl-aminofluorene (dG-C8-AF) in liver tissue were higher in GF rats (4.6 +/- 1.4 fmol/micrograms DNA) as compared to RM rats (2.6 +/- 0.04) or HM rats (2.0 +/- 0.7). In lung tissue and white blood cells a similar influence of the intestinal microflora on DNA adduct levels was observed. These results suggest that the intestinal microflora cleaves conjugates of 2-AF or N-hydroxy-2-AF, thus facilitating enterohepatic recirculation of these compounds and enhancing the formation of reactive intermediates binding to Hb. The latter is not observed for DNA adduct formation, indicating that most of these adducts have been formed after a single passage through the liver. After treatment with 2-NF, Hb and DNA adduct levels were much lower. An adduct spot was observed that was not present in rats that received 2-AF. In GF animals only very low levels of DNA adducts co-migrating with dG-C8-AF or deoxyguanosin-8-yl-acetyl-aminofluorene and no Hb adducts were observed, indicating that the metabolic activity of the microflora is an essential step in both Hb and DNA adduct formation.

Background: Conversion symptoms with a neurological character are not unusual in children. Little is known about prognosis. This study aimed to determine the outcome in a group of children with conversion., Patients and Methods: Over the period 1979-1989 35 children from 6 to 16 who met DSM-III-R criteria for conversion were selected from the case-records of the Child Neurology department of the University Hospital in Leiden. Case histories were analysed and 20 patients were interviewed at home and a standard questionnaire was used additionally., Results: Conversion symptoms disappeared with time in 15 patients. In comparison with the control group, patients with conversion scored higher on nervousness., Conclusion: Conversion disorder runs a favourable course. The place of child psychiatric treatment should be analysed prospectively.

Segmented, filamentous bacteria (SFBs) form a group of bacteria with similar morphology and are identified on the basis of their morphology only. The relationships of these organisms are unclear as the application of formal taxonomic criteria is impossible currently due to the lack of an in vitro technique to culture SFBs. The intestine of laboratory animals such as mice, rats, chickens, dogs, cats and pigs is known to harbour SFBs. To see whether this extends to other animal species, intestines from 18 vertebrate species, including man, were examined. SFBs were detected with light microscopy in the cat, dog, rhesus monkey, crab-eating macaque, domestic fowl, South African claw-footed toad, carp, man, laboratory mouse and rat, wood mouse, jackdaw and magpie. These results suggest that non-pathogenic SFBs are ubiquitous in the animal kingdom. Among apparently identical animals, there was considerable variation in the degree of SFB colonization. It is suggested that SFB colonization could serve as a criterion of standardization of laboratory animals.

Segmented filamentous bacteria (SFBs) are apathogenic autochthonous bacteria in the murine small intestine that preferentially attach to Peyer's patch epithelium. SFBs have never been cultured in vitro. We have studied the effects of SFBs on the immune system of the host. Mice monoassociated with SFBs were compared with germ-free mice and with mice without SFBs but with a specific-pathogen-free (SPF) gut flora. SFBs versus no microbial flora raised the number of lymphoid cells in the lamina propria of the ileal and cecal mucosa, raised the number of immunoglobulin A (IgA)-secreting cells in the intestinal mucosa, produced elevated IgA titers in serum and intestinal secretions, and enhanced the concanavalin A-induced proliferative responses of mesenteric lymph node cells. The SPF flora had effects similar to but less pronounced than those mediated by SFBs. The results indicate that SFBs stimulate the mucosal immune system to a greater extent than do other autochthonous gut bacteria.

Segmented, filamentous bacteria (SFBs) are autochthonous, apathogenic inhabitants of the ileum of various animal species. Outbred Swiss (Cpb:SE) mice have significantly higher degrees of SFB colonization than do inbred BALB/c mice. The present studies were carried out to identify determinants of this strain difference. In a cross-fostering experiment it was shown that SFB colonization of the pups is determined by the strain of the pups themselves rather than by the strain of the nursing dam. Thus, maternal effects may not be involved in SFB colonization. In a cross-infecting experiment using germ-free and SFB-positive animals of the two mouse strains, it was found that ileal SFB colonization is determined by host characteristics rather than by origin of the SFBs. Thus, SFBs that are specific for a given mouse strain may not exist in the two strains of mice. It is concluded that the mouse strain difference in SFB colonization is determined by host characteristics, which probably have a genetic basis.

Segmented, filamentous bacteria (SFBs) are autochthonous, apathogenic bacteria, occurring in the ileum of mice and rats. Although the application of formal taxonomic criteria is impossible due to the lack of an in vitro technique to culture SFBs, microbes with a similar morphology, found in the intestine of a wide range of vertebrate and invertebrate host species, are considered to be related. SFBs are firmly attached to the epithelial cells of the distal ileal mucosa, their preferential ecological niche being the epithelium covering the Peyer's patches. Electron microscopic studies have demonstrated a considerable morphological diversity of SFBs, which may relate to different stages of a life cycle. Determinants of SFB colonization in vivo are host species, genotypical and phenotypical characteristics of the host, diet composition, environmental stress and antimicrobial drugs. SFBs can survive in vitro incubation, but do not multiply. On the basis of their apathogenic character and intimate relationship with the host, it is suggested that SFBs contribute to development and/or maintenance of host resistance to enteropathogens.

Streptococcal cell wall (SCW)-induced arthritis is a chronic, erosive polyarthritis that can be induced in susceptible Lewis rats by one i.p. injection of an aqueous, sterile suspension of SCW. F344 rats are resistant to chronic joint inflammation. Our previous studies showed a correlation between susceptibility to SCW-induced arthritis and the ability to mount SCW-specific T cell responses, suggesting tolerance to SCW as a putative mechanism. Here we prevented the induction of tolerance to bacterial epitopes in F344 rats by using them germ-free and analysed susceptibility to arthritis subsequently. In addition, we conventionalized germ-free F344 rats at different times before induction of arthritis. Our results show that germ-free F344 rats are susceptible to SCW-induced arthritis with a similar severity, chronicity, incidence and onset as Lewis rats. Moreover, T cells isolated from germ-free F344 rats were able to respond to SCW. Conventionalization dramatically moderates arthritis and makes T cells unresponsive to SCW again. Thus, in normal rats (F344) a state of tolerance to arthritogenic epitopes is induced (neonatally) and maintained through life by the bacterial flora, resulting in resistance to bacterium-induced arthritides. In arthritis-prone (Lewis) rats, this tolerance is deficient and/or easily broken.

The appearance of segmented, filamentous bacteria (SFBs) in the small bowel of mice is influenced by the composition of the diet, but the dietary components responsible are not known. The addition of ground, whole Phaseolus vulgaris to a natural-ingredient diet at the expense of part of the skim milk powder, ground barley and wheat middlings components, caused an increase of the colonization of the mouse small bowel by SFBs. This effect was not seen when whole Phaseolus was added to a purified diet at the expense of part of the casein, corn oil, coconut fat, corn starch, dextrose and cellulose components. In an attempt to identify the fraction of Phaseolus that might contain SFB-inducing substances, the skin and kernel fraction of the bean were added to the natural-ingredient diet. The skin and kernel fraction were found to be as effective in inducing SFB appearance as was whole Phaseolus.

After oral administration of 5-aminosalicylic acid a substantial proportion of the acetylated form is excreted in the faeces. We have studied the role of the faecal microflora in acetylating 5-aminosalicylic acid. In faeces incubated under both aerobic and anaerobic conditions there was acetylation of 5-aminosalicylic acid. Of the anaerobic bacteria isolated from a 10(8) faecal dilution 44% were able to acetylate 5-aminosalicylic acid. We conclude that the normal faecal microflora contribute to the acetylation of 5-aminosalicylic acid.

Gut bacteria have been incriminated as causing or contributing to generalized sepsis with multiple organ failure in severely ill patients, and selective decontamination of the gastrointestinal tract of Enterobacteriaceae has been claimed to decrease septic complications in these patients. We studied the effects of selective decontamination of the gastrointestinal tract on survival and organ function in an experimental model of sepsis with multiple organ failure. Wistar rats were inoculated intraperitoneally with zymosan and randomized into control or treatment groups (trimethoprim or streptomycin sulfate). Selective decontamination effectively prevented bacterial translocation of Enterobacteriaceae. However, only early mortality was decreased, and only so in the streptomycin-treated rats. Selective decontamination did not result in a significantly better condition of the surviving animals on day 12.