[Bell's palsy: a broad differential diagnosisHouse-Brackmann-schaal]. / Bellse parese: een brede differentiaaldiagnose.

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. Score INormale functie van aangezicht op alle gebieden Score II Globaal: lichte zwakte bij nauwkeurig onderzoek; mogelijk zeer lichte synkinesieën. In rust: normale symmetrie en tonus. Motoriek: - Voorhoofd: matig tot goede functie. - Oog: volledige sluiting met minimale inspanning. - Mond: lichte asymmetrie. Score IIIGlobaal: duidelijke, maar niet-ontsierend verschil tussen twee zijdes; opvallende, maar geen ernstige synkinesieën, contracturen of hemifacialisspasmen. In rust: normale symmetrie en tonus. Motoriek: - Voorhoofd: lichte tot matige beweging. - Oog: volledige sluiting met inspanning. - Mond: lichte zwakte met maximale inspanning. Score IV Globaal: duidelijke zwakte of ontsierende asymmetrie. In rust: normale symmetrie en tonus. Motoriek: - Voorhoofd: geen. - Oog: onvolledige sluiting. - Mond: asymmetrie met maximale inspanning. Score V Globaal: nauwelijks waarneembare beweging. In rust: asymmetrie. Motoriek: - Voorhoofd: geen. - Oog: onvolledige sluiting. - Mond: lichte beweging. Score VI Geen beweging.

Pulmonary inflammation promoted by type-2 dendritic cells is a feature of human and murine schistosomiasis.

Schistosomiasis is a parasitic disease affecting over 200 million people in multiple organs, including the lungs. Despite this, there is little understanding of pulmonary immune responses during schistosomiasis. Here, we show type-2 dominated lung immune responses in both patent (egg producing) and pre-patent (larval lung migration) murine Schistosoma mansoni (S. mansoni) infection. Human pre-patent S. mansoni infection pulmonary (sputum) samples revealed a mixed type-1/type-2 inflammatory cytokine profile, whilst a case-control study showed no significant pulmonary cytokine changes in endemic patent infection. However, schistosomiasis induced expansion of pulmonary type-2 conventional dendritic cells (cDC2s) in human and murine hosts, at both infection stages. Further, cDC2s were required for type-2 pulmonary inflammation in murine pre-patent or patent infection. These data elevate our fundamental understanding of pulmonary immune responses during schistosomiasis, which may be important for future vaccine design, as well as for understanding links between schistosomiasis and other lung diseases.

[Bell's palsy: a broad differential diagnosis]. / Bellse parese: een brede differentiaaldiagnose.

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.

Dynamics of the bacterial gut microbiota during controlled human infection with Necator americanus larvae.

Hookworms are soil-transmitted helminths that use immune-evasive strategies to persist in the human duodenum where they are responsible for anemia and protein loss. Given their location and immune regulatory effects, hookworms likely impact the bacterial microbiota. However, microbiota studies struggle to deconvolute the effect of hookworms from confounders such as coinfections and malnutrition. We thus used an experimental human hookworm infection model to explore temporal changes in the gut microbiota before and during hookworm infection. Volunteers were dermally exposed to cumulative dosages of 50, 100 or 150 L3 Necator americanus larvae. Fecal samples were collected for microbiota profiling through 16S rRNA gene amplicon sequencing at weeks zero, four, eight, fourteen and twenty. During the acute infection phase (trial week zero to eight) no changes in bacterial diversity were detected. During the established infection phase (trial week eight to twenty), bacterial richness (Chao1, p = .0174) increased significantly over all volunteers. No relation was found between larval dosage and diversity, stability or relative abundance of individual bacterial taxa. GI symptoms were associated with an unstable microbiota during the first eight weeks and rapid recovery at week twenty. Barnesiella, amongst other taxa, was more abundant in volunteers with more GI symptoms throughout the study. In conclusion, this study showed that clinical GI symptoms following N. americanus infection are associated with temporary microbiota instability and relative abundance of specific bacterial taxa. These results suggest a possible role of hookworm-induced enteritis on microbiota stability.

Value of Endolymphatic Hydrops and Perilymph Signal Intensity in Suspected Ménière Disease.

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.

[A patient with both cocaine-induced nasal septum destruction and antibodies against anti-neutrophil cytoplasmic antibodies (ANCA); potential confusion with Wegener's disease]. / Een patiënt met neusseptumdestructie door cocaïne en antistoffen tegen cytoplastische antigenen van neutrofiele granulocyten (ANCA); mogelijke verwarring met de ziekte van Wegener.

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.

Recombinant human erythropoietin attenuates weight loss in a murine cancer cachexia model.

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.

Slide tracheoplasty for congenital tracheal stenosis.

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.

Faecal bacterial profile, nitrogen excretion and mineral absorption in healthy dogs fed supplemental oligofructose.

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.

Production of anti-CD3 and anti-CD7 ricin A-immunotoxins for a clinical pilot study.

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.

Neuromuscular disorders in patients with intermittent claudication.

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.

Effect of endotoxin on the advancing front between cultured middle ear mucosa and epidermis. A preliminary study.

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.

Nitroreduction and formation of hemoglobin adducts in rats with a human intestinal microflora.

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.

Role of the intestinal microflora in the formation of DNA and haemoglobin adducts in rats treated with 2-nitrofluorene and 2-aminofluorene by gavage.

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.

[Neurological conversion disorders in older children]. / Neurologische conversiestoornissen bij oudere kinderen.

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.

Intestinal, segmented, filamentous bacteria in a wide range of vertebrate species.

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.

Apathogenic, intestinal, segmented, filamentous bacteria stimulate the mucosal immune system of mice.

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.

Different degree of ileal colonization by segmented, filamentous bacteria in two strains of mice.

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.

Intestinal, segmented, filamentous bacteria.

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.

Gut flora induces and maintains resistance against streptococcal cell wall-induced arthritis in F344 rats.

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.