The cuticle: Not only a barrier for plant defence: A novel defence syndrome in plants with cuticular defects.

The cuticle is a physical barrier that prevents water loss and protects against irradiation, xenobiotics and pathogens. This classic textbook statement has recently been revisited and several observations were made showing that this dogma falls short of being universally true. Both transgenic Arabidopsis thaliana lines expressing cell wall-targeted fungal cutinase (so-called CUTE plants) or lipase as well as several A. thaliana mutants with altered cuticular structure remained free of symptoms after an inoculation with Botrytis cinerea. The alterations in cuticular structure lead to the release of fungitoxic substances and changes in gene expression that form a multifactorial defence response. Several models to explain this syndrome are discussed.

The neonatal Fc receptor is not required for mucosal infection by mouse mammary tumor virus.

The milk-borne mouse mammary tumor virus (MMTV) infects newborn mice via the intestine. Infection is initially restricted to Peyer's patches and later spreads to the epithelial cells of the mammary gland. The receptor that mediates uptake and transport of MMTV across the intestinal barrier has not yet been identified, The neonatal Fc receptor (nFcR), which is expressed by enterocytes during the first two weeks of life, is downregulated at weaning, and its disappearance correlates with the onset of intestinal resistance to MMTV. To test whether the nFcR mediates transport and allows infection, we foster nursed on infected MMTV mothers beta2 microglobulin-deficient (beta2m-deficient) newborn mice that are unable to express the nFcR at the surface of their enterocytes. Exposure of beta2m-deficient mice to milk-borne virus resulted in the deletion of peripheral blood T cells reactive to the superantigen encoded by MMTV. Since beta2m-deficient newborn mice are susceptible to MMTV infection despite the lack of the nFcR, we conclude that the nFcR is not required for MMTV transport.

Jaffé-Campanacci syndrome: an extremely rare cause of pathologic fracture of the femur

Introduction: Non-ossifying fibromas are common benign bone tumors of children and young adults. They are usually single, asymptomatic and regress spontaneously in adulthood. Some rare cases of pathologic fractures have been described. Jaffé-Campanacci syndrome is the association of multiple non-ossifying fibromas, "café-au-lait" spots and some degree of type 1 neurofibromatosis. While the relationship between the two entities remains unclear, there seems to be some genetic similarities (partial or complete deletion of the gene NF1). Case Report: A 17 yo female patient with a neurofibromatosis type 1 was referred to our tertiary centre with a pathologic fracture of the distal femur through a non-ossifying fibroma. She had a slight mental retardation and "café-au-lait" spots. Imaging revealed multiple typical non-ossifying fibromas of both distal femurs and proximal tibias. There was no impending fracture of the controlateral side, and no other findings on thoraco-abdominal CT scanner. The fracture was treated by minimal invasive plate osteosynthesis. Histological analysis of tissue samples taken during the intervention confirmed the histologic diagnosis of non-ossifying fibroma. The fracture healed eventless and the patient returned to work after 3 months. At 12 months follow-up, the patient remained pain-free. Imaging revealed remodelling of the lesions. Conclusion: Jaffé-Campanacci syndrome is an extremely rare cause of pathologic femur fracture. These fractures can be treated like any other, and good outcome is expected. There is still no consensus in regards to definition of the disease and its relationship with type 1 neurofibromatosis.

Absence of the fourth cranial nerve in congenital Brown syndrome.

PURPOSE: To elucidate the aetiology of congenital Brown syndrome. METHODS: Four consecutive patients diagnosed with unilateral congenital Brown syndrome had a comprehensive standardized ocular motility examination. Any compensatory head posture was measured. Brain magnetic resonance imaging (MRI) with regard for the IV cranial nerve (CN) was performed in all patients. Orbital MRI was performed in 2/4 patients, with images acquired in eight directions of gaze and superior oblique (SO) muscle areas compared. RESULTS: CN IV could not be identified bilaterally in two patients, but was absent only on the side of the Brown syndrome in the two other patients. On the normal side, orbital MRI revealed a smaller SO muscle area in upgaze than in downgaze, demonstrating normal actions of this muscle. On the side of the Brown syndrome, the SO area remained the same in upgaze and in downgaze and approximately symmetric to the area of SO in downgaze on the normal side. CONCLUSIONS: These cases add further anatomical support to the theory of paradoxical innervation in congenital Brown syndrome. CN IV was absent in two patients on the side of the Brown syndrome, but without muscle hypoplasia. SO muscle size did not vary in up- and downgaze, which we interpreted as a sign of constant innervation through branches of CN III.

Fourteen new cases contribute to the characterization of the 7q11.23 microduplication syndrome.

Interstitial deletions of 7q11.23 cause Williams-Beuren syndrome, one of the best characterized microdeletion syndromes. The clinical phenotype associated with the reciprocal duplication however is not well defined, though speech delay is often mentioned. We present 14 new 7q11.23 patients with the reciprocal duplication of the Williams-Beuren syndrome critical region, nine familial and five de novo. These were identified by either array-based MLPA or by array-CGH/oligonucleotide analysis in a series of patients with idiopathic mental retardation with an estimated population frequency of 1:13,000-1:20,000. Variable speech delay is a constant finding in our patient group, confirming previous reports. Cognitive abilities range from normal to moderate mental retardation. The association with autism is present in five patients and in one father who also carries the duplication. There is an increased incidence of hypotonia and congenital anomalies: heart defects (PDA), diaphragmatic hernia, cryptorchidism and non-specific brain abnormalities on MRI. Specific dysmorphic features were noted in our patients, including a short philtrum, thin lips and straight eyebrows. Our patient collection demonstrates that the 7q11.23 microduplication not only causes language delay, but is also associated with congenital anomalies and a recognizable face.

Role of bradykinin in the neonatal renal effects of angiotensin converting enzyme inhibition.

The vascular effects of angiotensin converting enzyme inhibitors are mediated by the inhibition of the dual action of angiotensin converting enzyme (ACE): production of angiotensin II and degradation of bradykinin. The deleterious effect of converting enzyme inhibitors (CEI) on neonatal renal function have been ascribed to the elevated activity of the renin-angiotensin system. In order to clarify the role of bradykinin in the CEI-induced renal dysfunction of the newborn, the effect of perindoprilat was investigated in anesthetized newborn rabbits with intact or inhibited bradykinin B2 receptors. Inulin and PAH clearances were used as indices of GFR and renal plasma flow, respectively. Perindoprilat (20 microg/kg i.v.) caused marked systemic and renal vasodilation, reflected by a fall in blood pressure and renal vascular resistance. GFR decreased, while urine flow rate did not change. Prior inhibition of the B2 receptors by Hoe 140 (300 microg/kg s.c.) did not prevent any of the hemodynamic changes caused by perindoprilat, indicating that bradykinin accumulation does not contribute to the CEI-induced neonatal renal effects. A control group receiving only Hoe 140 revealed that BK maintains postglomerular vasodilation via B2 receptors in basal conditions. Thus, the absence of functional B2 receptors in the newborn was not responsible for the failure of Hoe 140 to prevent the perindoprilat-induced changes. Species- and/or age-related differences in the kinin-metabolism could explain these results, suggesting that in the newborn rabbit other kininases than ACE are mainly responsible for the degradation of bradykinin.

Exome sequencing identifies DYNC2H1 mutations as a common cause of asphyxiating thoracic dystrophy (Jeune syndrome) without major polydactyly, renal or retinal involvement.

BACKGROUND: Jeune asphyxiating thoracic dystrophy (JATD) is a rare, often lethal, recessively inherited chondrodysplasia characterised by shortened ribs and long bones, sometimes accompanied by polydactyly, and renal, liver and retinal disease. Mutations in intraflagellar transport (IFT) genes cause JATD, including the IFT dynein-2 motor subunit gene DYNC2H1. Genetic heterogeneity and the large DYNC2H1 gene size have hindered JATD genetic diagnosis. AIMS AND METHODS: To determine the contribution to JATD we screened DYNC2H1 in 71 JATD patients JATD patients combining SNP mapping, Sanger sequencing and exome sequencing. RESULTS AND CONCLUSIONS: We detected 34 DYNC2H1 mutations in 29/71 (41%) patients from 19/57 families (33%), showing it as a major cause of JATD especially in Northern European patients. This included 13 early protein termination mutations (nonsense/frameshift, deletion, splice site) but no patients carried these in combination, suggesting the human phenotype is at least partly hypomorphic. In addition, 21 missense mutations were distributed across DYNC2H1 and these showed some clustering to functional domains, especially the ATP motor domain. DYNC2H1 patients largely lacked significant extra-skeletal involvement, demonstrating an important genotype-phenotype correlation in JATD. Significant variability exists in the course and severity of the thoracic phenotype, both between affected siblings with identical DYNC2H1 alleles and among individuals with different alleles, which suggests the DYNC2H1 phenotype might be subject to modifier alleles, non-genetic or epigenetic factors. Assessment of fibroblasts from patients showed accumulation of anterograde IFT proteins in the ciliary tips, confirming defects similar to patients with other retrograde IFT machinery mutations, which may be of undervalued potential for diagnostic purposes.

La maladie des vibrations [The vibration syndrome].

The vibration syndrome is an often unrecognized occupational neurovascular disease with a prevalence of more than 70% in certain high-risk occupations. Early recognition is crucial because continued exposure to vibration can lead to irreversible ischemic injury and loss of digits. Digital ischemia due to the vibration syndrome may be due to a vasospastic phenomenon, an organic microangiopathy or arterial thrombosis. Demyelinating neuropathy and carpal tunnel syndrome are often associated. Many pathophysiological mechanisms are implicated: hyperactivity of the central sympathetic nervous system, release of plasma endothelin-1 and loss of calcitonin-gene-related-peptide vasoregulation. Investigation tests, treatment and the European Community Directive for the protection of workers are also presented.

The association of aldosterone with obesity-related hypertension and the metabolic syndrome.

Overweight and obesity are associated with arterial hypertension. Given the large increase in the obesity prevalence worldwide, the number of obese patients with hypertension is likely to increase substantially in the near future. Overweight and obese patients are exposed to an important metabolic and cardiovascular risk. The understanding of the mechanisms linking obesity to hypertension is important for specific prevention and therapy in this population. There is some evidence that obesity is associated with an increased aldosterone level. To date, 2 mechanisms may explain the interaction of fat tissue with the renin-angiotensin-aldosterone system, and therefore explain, in part, obesity-related hypertension. First, human adipose tissue produces several components of the renin-angiotensin-aldosterone system, mainly adipose tissue-derived angiotensinogen. Second, increased fatty acid production in the obese patient, especially nonesterified fatty acids, might stimulate aldosterone production, independent of renin. A better understanding of these mechanisms might have implications for the management of hypertension in overweight and obese patients. Because aldosterone also is associated with blood glucose and blood lipids, selective aldosterone blockade may represent a particularly attractive therapeutic strategy in obese patients with a clustering of cardiovascular risk factors.

Prise en charge du syndrome post-thrombotique [Management of post-thrombotic syndrome].

Post-thrombotic syndrome (PTS) is the most frequent chronic complication of deep vein thrombosis with an estimated prevalence of 30-50%. PTS is a significant cause of disability, especially when complicated by venous ulcers. Therefore, it has important socio-economic consequences for both the patient and the health care system. Aim of this review is to resume state of the art literature on the management of PTS.

Speech and oromotor deficits of epileptic origin in benign partial epilepsy of childhood with rolandic spikes (BPERS). Relationship to the acquired aphasia-epilepsy syndrome.

The authors report three children who suffered temporary oromotor or speech disturbances as focal epileptic manifestations within the frame of benign partial epilepsy of childhood with rolandic spikes and review similar cases described in the literature. The deficit can occur as an initial symptom of the disorder without visible epileptic seizures and interferes in a variable way with simple voluntary oromotor functions or complex movements including speech production, depending on the exact location and spread of the discharging epileptic focus around the perisylvian region. The most severe deficit produces the anterior operculum syndrome. More subtle non-linguistic deficits such as intermittent drooling, oromotor apraxia or dysfluency, as well as linguistic ones involving phonologic production, can occur. The rapidity of onset, progression and recovery of the deficit is very variable as well as its duration and presumably reflects the degree of epileptic activity. In some cases, rapid improvement with antiepileptic medication occurs and coincidence between the paroxysmal EEG activity (which is usually bilateral) and the functional deficit is seen. The clinical and EEG profile of the seizures disorder and the dynamic of the deficit in these cases bear a strong resemblance to what is seen in the acquired epilepsy-aphasia syndrome (Landau and Kleffner). The variations in clinical symptoms appear more related to the main site, local extension and bilaterality of the epileptic foci rather than a basic difference in physiopathology.

Fat embolism syndrome after combined aesthetic surgery.

Fat embolism syndrome is a rare complication that develops after extended soft tissue disruption by liposuction, in particular if combined with time consuming, multiple procedures. Early signs are non-specific and often not considered, so that diagnosis and correct management may be delayed. We report a case in which liposuction combined with other aesthetic surgical procedures caused a fat embolism syndrome in a 46-year-old woman, which was followed by multiple organ failure and the development of sepsis with perimammary abscesses. Extended liposuction of the abdomen and thighs, bilateral augmentation mammaplasty, and stripping of both greater saphenous veins were combined.

La ventilation non invasive dans l'insuffisance respiratoire aiguë : de la broncho-pneumonie chronique obstructive au syndrome de détresse respiratoire aiguë

RESUME : L'application d'une ventilation non-invasive (VNI) à pression positive chez des patients avec une insuffisance respiratoire aiguë hypoxémique non liée à une broncho-pneumopathie chronique obstructive (BPCO), reste controversée malgré les résultats encourageants apparus dans de récentes études. Ce travail de thèse est composé d'une introduction qui comprend un historique de la VNI et une revue de ces applications principales dans l'insuffisance respiratoire aiguë avec, en particulier, une analyse des études cliniques principales concernant son utilisation dans l'exacerbation de la BPCO, dans l'asthme aigu sévère, dans les syndromes restrictifs et dans l'insuffisance respiratoire aiguë hypoxémique. La première partie aborde également les aspects pratiques de l'utilisation de la VNI, avec une description de l'équipement et des techniques utilisées. Ce travail de thèse a ensuite pour but d'analyser dans une étude personnelle l'application d'une VNI à pression positive chez des patients avec une insuffisance respiratoire aiguë hypoxémique non liée à une BPCO. Il s'agit d'une étude prospective et observationnelle, dans laquelle nous avons voulu analyser l'efficacité de la VNI chez un groupe de patients sélectionnés et coopérants, stables du point de vue hémodynamique, présentant un syndrome de détresse respiratoire aiguë (SDRA) primaire (atteinte pulmonaire directe). Les échanges gazeux, le taux d'intubation, la mortalité et la durée de séjour dans l'unité de soins intensifs ont été enregistrés. Dans notre travail, la VNI a été appliquée de manière prospective à 12 patients, stables du point de vue hémodynamique, présentant les critères diagnostiques pour un SDRA primaire (SDRAP) et une indication pour une ventilation mécanique classique. Leur évolution a été comparée avec celle d'un groupe contrôle de 12 patients avec SDRAP. et précédemment traités dans la même unité de soins intensifs, ayant des caractéristiques similaires à l'admission : âge, score SAPS II, rapport Pa02/Fi02 et valeurs de pH . Un échec de la VNI fut observé chez 4 patients (33%), tous bactériémiques et nécessitant une intubation endotrachéale. Un facteur prédictif négatif. Les patients traités avec succès ont présenté un temps cumulatif de ventilation (p=0.001) et une durée de séjour aux soins intensifs (p=0.004) inférieure à ceux du groupe contrôle. Pendant la première période d'observation de la ventilation, l'oxygénation après 60 minutes s'est améliorée de manière plus importante dans le groupe VNI par rapport au groupe contrôle (PaO2/FiO2 : 146 +/- 52 mmHg vs. 109 +/- 34 mmHg ; p=0.05). Le taux de mortalité globale aux soins intensifs ne fut pas différent entre le groupe VNI et le groupe de patients intubés. Le taux de complications graves fut plus élevé chez les patients du groupe contrôle. Nos résultats suggèrent que chez des patients stables et coopérants, avec une pneumonie étendue, sans bactériémie à l'admission et remplissant les critères diagnostiques d'un SDRAp, la VNI représente une alternative valable à l'intubation endotrachéale.

Gastrointestinal complications of post-diarrheal hemolytic uremic syndrome.

PURPOSE: Whereas gastrointestinal symptoms such as vomiting, diarrhea and abdominal pain are common in children suffering from the so-called post-diarrheal form (D+) of hemolytic uremic syndrome (HUS), more serious gastrointestinal complications are rare. We tried to define factors predictive of the severity of gastrointestinal complications post D+ HUS. METHODS: We reviewed the files of all children admitted to our hospital for D+ HUS between 1988 and 2000. We retained those cases with gastrointestinal complications and analyzed the consequences of these complications on the evolution of the children's conditions. RESULTS: Sixty-five children with D+ HUS were admitted to our hospital during this period. Sixteen children developed gastrointestinal complications involving one or more digestive organs: necrosis of the colon or ileum, hemorrhagic colitis, pancreatitis, transient diabetes, hepatic cytolysis and cholestasis, peritonitis and prolapse of the rectum. One child died. CONCLUSION: Gastrointestinal complications of D+ HUS are rare, but they can be lethal, and early surgery may sometimes prove necessary. However, we were not able to demonstrate a correlation between the severity of the gastrointestinal manifestations and the clinical or biological signs accompanying D+ HUS.

Pancreatic stone protein as a novel marker for neonatal sepsis.

PURPOSE: Early-onset sepsis (EOS) is one of the main causes for the admission of newborns to the neonatal intensive care unit. However, traditional infection markers are poor diagnostic markers of EOS. Pancreatic stone protein (PSP) is a promising sepsis marker in adults. The aim of this study was to investigate whether determining PSP improves the diagnosis of EOS in comparison with other infection markers. METHODS: This was a prospective multicentre study involving 137 infants with a gestational age of >34 weeks who were admitted with suspected EOS. PSP, procalcitonin (PCT), soluble human triggering receptor expressed on myeloid cells-1 (sTREM-1), macrophage migration inhibitory factor (MIF) and C-reactive protein (CRP) were measured at admission. Receiver-operating characteristic (ROC) curve analysis was performed. RESULTS: The level of PSP in infected infants was significantly higher than that in uninfected ones (median 11.3 vs. 7.5 ng/ml, respectively; p = 0.001). The ROC area under the curve was 0.69 [95 % confidence interval (CI) 0.59-0.80; p < 0.001] for PSP, 0.77 (95 % CI 0.66-0.87; p < 0.001) for PCT, 0.66 (95 % CI 0.55-0.77; p = 0.006) for CRP, 0.62 (0.51-0.73; p = 0.055) for sTREM-1 and 0.54 (0.41-0.67; p = 0.54) for MIF. PSP independently of PCT predicted EOS (p < 0.001), and the use of both markers concomitantly significantly increased the ability to diagnose EOS. A bioscore combining PSP (>9 ng/ml) and PCT (>2 ng/ml) was the best predictor of EOS (0.83; 95 % CI 0.74-0.93; p < 0.001) and resulted in a negative predictive value of 100 % and a positive predictive value of 71 %. CONCLUSIONS: In this prospective study, the diagnostic performance of PSP and PCT was superior to that of traditional markers and a combination bioscore improved the diagnosis of sepsis. Our findings suggest that PSP is a valuable biomarker in combination with PCT in EOS.