The association of Greig syndrome and mastocytosis reveals the involvement of the hedgehog pathway in advanced mastocytosis.

Mastocytosis is a heterogeneous disease characterized by an abnormal accumulation of mast cells (MCs) in 1 or several organs. Although a somatic KIT D816V mutation is detected in ∼85% of patients, attempts to demonstrate its oncogenic effect alone have repeatedly failed, suggesting that additional pathways are involved in MC transformation. From 3 children presenting with both Greig cephalopolysyndactyly syndrome (GCPS, Mendelian Inheritance in Man [175700]) and congenital mastocytosis, we demonstrated the involvement of the hedgehog (Hh) pathway in mastocytosis. GCPS is an extremely rare syndrome resulting from haploinsufficiency of GLI3, the major repressor of Hh family members. From these familial cases of mastocytosis, we demonstrate that the Hh pathway is barely active in normal primary MCs and is overactive in neoplastic MCs. GLI3 and KIT mutations had a synergistic, tumorigenic effect on the onset of mastocytosis in a GCPS mouse model. Finally, Hh inhibitors suppressed neoplastic MC proliferation in vitro and extend the survival time of mice with aggressive systemic mastocytosis (ASM). This work revealed, for the first time, the involvement of Hh signaling in the pathophysiology of mastocytosis and demonstrated the cooperative effects of the KIT and Hh oncogenic pathways in mice with ASM, leading to the identification of new promising therapeutic targets.

Disruption of pathways regulated by Integrator complex in Galloway-Mowat syndrome due to WDR73 mutations.

Several studies have reported WDR73 mutations to be causative of Galloway-Mowat syndrome, a rare disorder characterised by the association of neurological defects and renal-glomerular disease. In this study, we demonstrate interaction of WDR73 with the INTS9 and INTS11 components of Integrator, a large multiprotein complex with various roles in RNA metabolism and transcriptional control. We implicate WDR73 in two Integrator-regulated cellular pathways; namely, the processing of uridylate-rich small nuclear RNAs (UsnRNA), and mediating the transcriptional response to epidermal growth factor stimulation. We also show that WDR73 suppression leads to altered expression of genes encoding cell cycle regulatory proteins. Altogether, our results suggest that a range of cellular pathways are perturbed by WDR73 loss-of-function, and support the consensus that proper regulation of UsnRNA maturation, transcription initiation and cell cycle control are all critical in maintaining the health of post-mitotic cells such as glomerular podocytes and neurons, and preventing degenerative disease.

Shigella infection in children under 5 years old in western French Guiana.

French Guiana, a tropical country, is characterised by a young and multi-ethnic population. Difficulties in accessing safe water sources lead to outbreaks of gastroenteritis. The objectives of this study were (1) to describe the microbiological profile of shigella strains isolated in western French Guiana, including antimicrobial susceptibility and the distribution of strains in terms of species and serotypes and (2) to estimate the incidence of shigellosis in children under 5 years old. A retrospective observational study was conducted of 213 cases of shigellosis diagnosed in the biology department of the hospital centre for western French Guiana between 2000 and 2012 in children under 5 years old. The serogroups (formerly known as species) that predominates in French Guiana was Shigella flexneri. No resistance was observed to fluoroquinolones or to third-generation cephalosporins. The average incidence of shigellosis in children under 5 years old in western French Guiana was estimated at 189.6 cases per 100 000 inhabitants per year. Shigellosis is a public health problem in western French Guiana. These infections suggest the difficulties in accessing safe water sources and the lack of public sanitation. A quadrivalent vaccine containing Shigella sonnei and three serotypes of S. flexneri (S. flexneri 2a, 3a and 6) could provide broad coverage against shigella infections.

[Impact of the hyperthermic intraperitoneal chemotherapy on the fluid-electrolytes changes and on the acid-base balance]. / Retentissements hydroélectrolytiques et acidobasiques de la chimiohyperthermie intrapéritonéale.

BACKGROUND: Hyperthermic intraperitoneal chemoperfusion (HIPEC) is an innovative treatment of the peritoneal carcinomatosis with potential iatrogenicity. This observational study was designed to improve our understanding of HIPEC's impact on the renal and respiratory functions, on temperature, blood cells counts, body fluids/electrolytes and acid-base balance. METHODS: We retrospectively analyzed the perioperative care of 20 patients that underwent HIPEC with oxaliplatin (n=19) and mitomycin C (n=1). The abdominal cavity was filled with the peritoneal dialysis fluid with dextrose 5%: volume of 2L/m(2). Follow-up for the study was stopped on postoperative day 7. RESULTS: The main changes were appearing just after the HIPEC procedure: increased diuresis, lactic acidosis, hyponatremia and hyperglycaemia (despite aggressive intravenous insulin therapy). In our series, there was no renal failure or impact on blood cells counts until the 7(th) day, neither some changes on the arterial blood gases. CONCLUSION: Hyperglycemia might explain increased diuresis of lactic acidosis and the rapid installation of hyponatremia. Taken together, these results suggest that glycemic control must be improved in order to avoid the other metabolic disturbances.

Efficacy of the non-antibiotic paste Protexin Hoof-Care for topical treatment of digital dermatitis in dairy cows.

In this study, the efficacy of the non-antibiotic paste Protexin Hoof-Care containing metallic salts and organic acids, was tested for local treatment of 26 acute digital dermatitis lesions. The control group (26 cases) was treated with local application of oxytetracycline spray. These 52 affected limbs with digital dermatitis were diagnosed in 47 dairy cows from eight different farms with slatted floors. The therapeutic effect was evaluated using a scoring system for weightbearing at stance, lameness at walk and pain of the digital dermatitis lesions. The pre-treatment and control examination scores were documented on days 0, 4, 10 and 28. Both treatment regimens were effective, no statistical differences regarding the examined parameters was found between the group treated with the non-antibiotic Protexin Hoof-Care paste and the group treated with oxytetracycline spray. Twenty-seven digital dermatitis lesions required only one treatment with one of these products. A second topical treatment was carried out on day 4 in 13 lesions of the study group and in 12 lesions of the control group. The data of this pilot study indicate that the non-antibiotic paste Protexin Hoof-Care could be a valuable alternative to topical antibiotic treatment for digital dermatitis in dairy cattle.

Clinical and ultrasonographic findings in the mammary gland of sheep.

AIM: To compare clinical and ultrasonographic findings and assess the value of ultrasonography for evaluating the structure and condition of the teat and teat canal of sheep. METHODS: The mammary glands of 30 lactating ewes were examined clinically and using ultrasonography. The distance from the teat tip to the ground was measured and diagnostic images of the body of the gland, gland cistern and teat cistern were obtained using an 8.5 MHz frequency ultrasonic transducer. A California mastitis test (CMT) and bacteriological culture were performed on milk samples collected from each half of each udder. RESULTS: Udder parenchyma and teats were palpably normal in 27/30 (90%) ewes. Milk clots or abnormalities were evident in 4/30 (13%) udders, lesions in the glandular parenchyma and/or teats were evident by palpation in 3/30 (10%), and pathogenic bacteria were cultured from 2/30 (7%). In both of the latter cases, mastitis was diagnosed based on clotted and discoloured appearance of milk and highly positive CMT reactions. Ultrasonographic examination in these udders revealed non-homogenous regions in the glandular tissue and alternating areas of hyperechogenic and hypoechogenic tissue. Overall, highly positive CMT reactions were evident in milk from 14/30 (47%) left halves and 9/30 (30%) right halves (p=0.02). No relationship between teat-to-ground distances and CMT results was evident (p>0.05). Teat canal lengths ranged from 5.7-10.3 mm (mean=8.6; SD=1.3 mm) and the widths from 1.8-3.1 mm (mean=2.3; SD=0.4 mm). Milk sampled from ewes that had long (> or = 9 mm) or wide (> or = 2 mm) teat canals was highly positive to the CMT in 75% and 83% of cases, respectively. CONCLUSIONS: Ultrasonographic measurements of the length and width of the teat canal appeared to correlate with CMT results. The use of ultrasonography in evaluating the health of the udder of small ruminants holds promise for the future.

Ultrasonography of the teat canal in cows and sheep.

When the isolated teat of a cow was examined with an 8.5 MHz linear array transducer in a vertical plane, the teat canal appeared as a thin, white line, bordered on each side by parallel, thick, grey-black bands. In a horizontal plane a comparable image was obtained. In a sheep, images of comparable quality were obtained with a 12 MHz transducer. Histological studies of the tissues whose removal led to the disappearance of this characteristic ultrasonographic appearance showed that it was associated with the stratified keratinised squamous epithelium with distinct papillae. The content of keratin in the stratum corneum was apparently responsible for the bright zone; the stratum lucidum was not visible, and the surrounding dark, less echoic area was associated with the stratum granulosum. Doppler echography in live animals confirmed this designation. The outer layers of the teat wall were more echogenic.

[Sonography of the teat of cattle, sheep and goats in comparison with other methods of diagnostic imaging--a review]. / Sonographie der Zitze von Rind, Schaf und Ziege im Vergleich mit anderen bildgebenden Verfahren--eine Ubersicht.

Beside the clinical examination of udder/teat imaging methods e.g. sonography, radiography and endoscopy allow diagnosis. This publication will give a summary of currently used and potentially usable methods of diagnostic imaging applied to the teat. Advantages and disadvantages of the several methods were compared--as quoted in literature and completed by own experiences.

Assessment of the quality of radiographs in 44 veterinary clinics in Great Britain.

The quality of radiographic images, radiographic equipment and radiation safety were assessed objectively in 44 veterinary clinics in Great Britain, and a questionnaire was used to survey opinion on the general standard of radiography and aspects of the radiographic techniques used. Good or tolerable films were produced by 56 per cent of the clinics but there was a tendency to produce films that were too dark. Poor exposure factors were chosen in 49 per cent of the films. A significant number of films (27 per cent) were underdeveloped whereas only 11 per cent were overdeveloped. Many of the errors were due to operator error or inadequate technique, whereas, in the questionnaire, many clinics suggested that their problems were due mainly to faulty or inadequate equipment.

[Result of a European-wide inquiry about the use of artificial UV radiation sources in zoo animal husbandry with special regard to the mammals (Primates/Simiae/monkeys)]. / Ergebnis einer europaweiten Erhebung zum Einsatz künstlicher UV-Strahlungs-quellen in der Zootierhaltung mit besonderer Berücksichtigung der Mammalia (Primates/Simiae-Affen).

The geographical origin of many exotic animals are areas with intensive solar radiation. When brought into European zoological gardens, they might suffer under a deficiency of UV-radiation, especially in industrial areas with an high level of air pollution. 100 zoological gardens in middle and northern Europe were asked for information, whether artificial UV-sources are used in keeping animals or not; 57% answered: in 60% of the cases artificial UV-sources are used, in 40% not. The result of using artificial UV-sources in keeping reptiles will be published soon. This publication shows the use of artificial UV-sources for mammalians, with attention to Old World nonhuman primates and especially to New World nonhuman primates: this species cannot utilize vitamin D2 and so requires D3. Additionally to an adequate nutritional diet, the exposition is done whether as therapeutical treatment of metabolic bone diseases, or e.g. to rise the vitality and the fitness. The lamp type and the chosen exposure dates are very different; mostly chosen with one's own judgement. To assess the safe dose, having positive effects, i.g. the vitamin D-synthesis and avoiding any (skin-)damaging, the knowledge of many facts is requested: the comparison of the climatic conditions, albedo, the behaviour of the animals in sun, the conditions of keeping in zoo (cage/outdoor enclosure), influence on the appearance of the animals haircoat and skin (transmission rate for UV-radiation, pigmentation of skin a.o.) and the relation between dose and biological effect. Additionally the spectral distribution and the irradiance of artificial UV-sources has to be known. Further experimental work is necessary.

[Veterinary radiology in Germany, Switzerland and Austria: a comparative analysis of problems]. / Veterinärröntgenologie in Deutschland, Schweiz und Osterreich: Eine vergleichende Problemanalyse.

The result of an investigation in 1988/89 to grasp the problems of veterinary radiology in Austria left some uncertainties. By an enquiry of 200 vets (49% answered) additional information was received. A comparison between Austria, Germany and Switzerland revealed the same problems: neglected darkroom work. The causes are absent or not seldom false advice by medical/technical firms, the lacking willingness of vets to become advised, false parsimony and insufficient offer of meetings and seminars providing the physical know-how in producing X-ray pictures.

[The problems of X-ray image formation in veterinary practice--result of a cyclic study with the use of a test phantom for the determination of image quality]. / Die Problematik der Röntgenbilderzeugung in der tierärztlichen Praxis--Ergebnis eines Ringversuches unter Verwendung eines Testphantoms zur Bestimmung der Bildgüte.

To grasp the problems of producing X-ray pictures in veterinary surgery, a ring trial was carried out. The task of the veterinarians was to produce two radiographs: from a certain body region, together with a test phantom, which allowed the judgement of the image quality immediately. The dates and technique of exposure had to be chosen as usual, one picture had to be developed in the dark room, either manually--the usual way with the normally used chemicals or by automatic developing machine. The other picture was developed under standard conditions in the Institute of Medical Physics. For a third radiograph, already exposed with the correct dose, only development was requested. Therewith the total process of producing an x-ray picture, the exposure dates and -technique and the dark-room procedure should be analyzed. Additionally a protocol was drawn up. All results were treated anonymously. The outcome of the trial obviously showed the problems: blatant tendency to overexposure, in no case underexposure, combined with faults in the dark room--e.g. disregarding the condition of the developer or the probably given necessity of changing the developer and even the importance of controlling time and temperature during developing. No informations were requested about fixation- and stop bath or the method of drying.(ABSTRACT TRUNCATED AT 250 WORDS)

[The use of a test model in a stepped form (test steps) for the clarification of different problem situations in X-ray diagnosis. 2. The use of test steps for testing the POLAROID-TPX immediate X-ray picture system]. / Der Einsatz eines Testphantoms in treppenförmiger Gestalt (Testtrepe) zur Klärung verschiedener Problemstellungen in der Röntgendiagnostik. Teil 2: Der Einsatz der Testtreppe zur Prüfung des POLAROID-TPX-Röntgensofortbildsystems.

The stepwedge, described in part 1 and in other publications, was used for the examination of the POLAROID-Instant Radiographic System. The result showed, that this system is a quite acceptable method for the practitioner. POLAROID-radiographs, in comparison with the classic radiographs, show equal contrast and detail-visibility, but demand a higher radiation dose.

[The use of a test phantom in step-shaped forms (test steps) for the clarification of different problem situations in x-ray diagnosis. 1. The use of test steps for the estimation of image quality after modified darkroom technics]. / Der Einsatz eines Testphantoms in treppenförmiger Gestalt (Testtreppe) zur Klärung verschiedener Problemstellungen in der Röntgendiagnostik. Teil 1: Der Einsatz der Testtreppe zur Beurteilung der Bildgüte nach modifizierter Dunkelkammertechnik.

Properly exposed radiographs and under- or overexposed ones were processed differently with regard to temperature and time. Using a step wedge for the objective estimation, the alteration of well-exposed radiographs by neglecting time and temperature control was examined. Further information is given about the possibility to improve the quality of wrongly exposed radiographs by manipulation of the processing, and about the quantity of acceptable radiographs received in this way. Stop bath, fixation bath, wash bath and drying were performed regularly. The result showed, that the only chance to get high quality radiographs is by exact and correct working.

[A simple test phantom in the form of a staircase for running control of the image in veterinary roentgenology]. / Ein einfaches Testphantom in Gestalt einer Treppe zur laufenden Kontrolle der Bildgüte in der Veterinärröntgenologie.

Quality control in veterinary radiology seems to be neglected. For the correct estimation of the radiographic quality, there is no adequate phantom available. Although measurements have shown that the exposure to radiation is far under the admissible limits, the quantity of repeated examination has to be reduced. So it was necessary to create a phantom, which allows the objective judgement of the x-ray photograph taken immediately from the patient. The phantom shows the following characteristics: 1) It is small-sized, so that it can be represented on the radiograph together with the object, but without remarkable enlargement of the beam and additional exposure to radiation. 2) It consists of tissue-similar material, which absorbs and scatters x-rays similar to the body region. According to the fact that the indications for radiographs in veterinary medicine are mostly problems in skeleton regions, this region is represented first of all. 3) Therefore the phantom shows variable thickness, so that it can simulate different skeleton parts. 4) The represented parameters are: 4.1 the different radiographic densities; 4.2 the latitude; 4.3 the radiographic contrast; 4.4 the radiographic detail visibility (film-far, film-close) in the relevant parts of the x-ray picture 5) The phantom is universally applicable. By a way of "calibration" it is multipurpose for certain kinds and sizes of animals.

Role of ancillary properties of beta-adrenoceptor antagonists in protecting the heart from anoxia.

The mechanism of the cardioprotective action of beta-blocking drugs against anoxia or ischemia is still not clear. We used beta-blockers (5 x 10(-7) M) of various pharmacodynamic profiles in a model of isolated, perfused working guinea pig heart subjected to 20 min of anoxia to study this. The cardioprotective effects were evaluated by measuring the recovery of the flow indices after 15 min of reoxygenation. There was a significant cardioprotective action (as measured by the effect on stroke volume recovery and on recovery of other flow and work indices) of the beta-blocking properties (nadolol, P less than 0.05), of the membrane-stabilizing property [+)-propranolol, P less than 0.05) and of a combination of these two properties with (+/-)-propranolol, which had a significantly greater effect than nadolol (P less than 0.05). The addition of weak (acebutolol) or strong (pindolol) intrinsic partial agonist activity had no clear unfavourable effect, as the degree of cardioprotection was comparable with that obtained with (+/-)-propranolol. The stroke volume recovery (percent recovery after anoxia) in the control hearts was 42.57 +/- 12.75 compared to 54.84 +/- 6.94 in hearts pretreated with nadolol, 62.99 +/- 11.41 with (+)-propranolol, 71.02 +/- 11.36 with (+/-)-propranolol, 72.63 +/- 13.08 with acebutolol and 68.01 +/- 15.42 with pindolol. In vitro heart protection from anoxia with beta-blockers would appear to be related to beta-blocking activity and/or membrane stabilizing property but not a function of partial agonist activity. These ancillary properties of beta-blockers should thus be taken into account in studies on cardioprotection.

[Cardiac involvement in 2 cases of malignant non-Hodgkin's lymphoma. Course of cardiac involvement under chemotherapy]. / Atteinte cardiaque dans deux cas de lymphomes malins non hodgkiniens. Evolution de l'atteinte cardiaque sous chimiothérapie.

In a recently published post-mortem series the incidence of cardiac lesions in malignant lymphoma was estimated at about 8.7%. These lesions rarely produce specific cardiac symptoms; they usually are late manifestations of a disease with multiple secondary lesions or are discovered at autopsy. In most patients the lesions are not limited to the heart but represent the extension to that organ of a malignant lymphoma. We observed two cases of cardiac lesions secondary to malignant non-Hodgkin lymphoma and we were able to evaluate their response to chemotherapy. In the first patient the cardiac symptoms revealed the lymphoma; in the second patient the cardiac involvement was discovered 4 years after the lymphoma was diagnosed. In both cases the cardiac lesions were detected by two-dimensional echocardiography. They presented as polypoid masses filling the right atrium and associated with periaortic thickening in the first case, and as a large heterogeneous mass including a tricuspid valve leaflet and extending to the free wall of the right ventricle in the second case. Pericardial effusion was present in the two patients. These echocardiographic findings were confirmed computerized tomography and catheterization. In the first case, followed up for one year, the echocardiographic images reverted to normality after chemotherapy. The second patient, unfortunately, did not respond to chemotherapy and deteriorated rapidly.