Oedematous Reaction Research Articles

Fatal outcome after heart surgery in PMM2-CDG due to a rare homozygous gene variant with double effects

Variants in Phosphomannomutase 2 (PMM2) lead to PMM2-CDG, the most frequent congenital disorder of glycosylation (CDG). We here describe the disease course of a ten-month old patient who presented with the classical PMM2-CDG symptoms as cerebellar hypoplasia, retinitis pigmentosa, seizures, short stature, hepato- and splenomegaly, anaemia, recurrent vomiting and inverted mamillae. A severe form of tetralogy of Fallot was diagnosed and corrective surgery was performed at the age of 10 months. At the end of the cardiopulmonary bypass, a sudden oedematous reaction of the myocardium accompanied by biventricular pump failure was observed immediately after heparin antagonization with protamine sulfate. The patient died seven days after surgery, since myocardial function did not recover on ECMO support. We here describe the first patient carrying the homozygous variant g.18313A > T in the PMM2 gene (NG_009209.1) that either can lead to c.394A > T (p.I132F) or even loss of 100 bp due to exon 5 skipping (c.348_447del; p.G117Rfs*4) which is comparable to a null allele. Proliferation and doubling time of the patient's fibroblasts were affected. In addition, we show that the induction of cellular stress by elevating the cell culture temperature to 40 °C led to a decrease of the patients' PMM2 transcript as well as PMM2 protein levels and subsequently to a significant loss of residual activity. We assume that metabolic stressful processes occurring after cardiac surgery led to the drop of the patient's PMM activity below a life-sustaining niveau which paved the way for the fatal outcome.

Successful treatment of equine sarcoids with cisplatin electrochemotherapy: A retrospective study of 48 cases

Sarcoids are the commonest form of equine skin tumour. Several therapeutic measures have been described but none is considered to be universally effective. Electrochemotherapy (ECT) is a new anticancer therapy that utilises electrical field pulses to induce increased cell membrane permeability to antitumour hydrophilic drugs, such as cisplatin. The increased intracellular concentration of the drugs has a significant therapeutic benefit. The procedure has not been previously reported in a large number of horses. To validate ECT as a novel alternative treatment for equine sarcoids. A retrospective study evaluating the efficacy of cisplatin ECT in the treatment of equine sarcoids was performed. Electrochemotherapy treatments were applied under general anaesthesia at 2 week intervals with or without prior excision or debulking. Electric pulses were directly applied to the lesions following intra-tumoural injections of an aqueous solution of cisplatin. One-hundred-and-ninety-four sarcoids on 34 horses, 2 ponies, 11 donkeys and one mule were treated with ECT. The 4 year nonrecurrence rate was 97.9% for animals (47/48) and 99.5% (193/194) for tumours. When ECT was used as a single treatment, a significant influence of tumour size (ρ= 0.55) on the number of treatments required for cure was shown. When prior surgery was performed, there was a significant influence (P<0.001) of the excision quality (complete or incomplete) and the healing mode (closed or open wound) on the number of treatments. The most common adverse effect was a slight oedematous reaction for lesions located on thin skin regions. Results demonstrate that ECT, with or without concurrent tumour debulking, is an effective alternative for treatment of equine sarcoids.

Devascularization following endoscopic sclerotherapy of oesophageal varices: Dangers and difficulties

Twenty-three patients underwent devascularization operations for acute variceal bleeding. All had received endoscopic sclerotherapy, either long-term or just before surgery. The oesophagus and peri-oesophageal tissues showed either oedematous or fibrotic reaction depending on the number and duration of sessions of sclerotherapy. These changes in the oesophagus and surrounding tissues were responsible for intraoperative oesophageal perforation and postoperative anastomotic leaks. To obviate these problems, stapling of the anterior and posterior walls of the stomach was tried and found to be safer than stapled transection of the oesophagus. During follow-up, varices reappeared in over 75 per cent of patients and were managed by further sclerotherapy. Patients who did not receive sclerotherapy had a higher incidence of rebleeding.

MRI studies of the neurotoxic effects of l-2-chloropropionic acid on rat brain

l-2-Chloropropionic acid (l-CPA) is selectively toxic to rat cerebellar granule cells; necrosis is first observed about 36 hours after administration of l-CPA (750 mg/kg p.o.) becoming more marked by 48 h. Parallel to the onset of cell death an increase in cerebellar water content and sodium concentration has been reported suggesting an oedematous reaction. In this study T2-weighted (T2WI) and diffusion weighted (DWI) imaging were used to detect the development of neuronal damage in the cerebellum of rats as a result of exposure to l-CPA. T2WI and DWI were not able to detect cerebellar abnormalities at 37 h post-dosing except for a slight swelling of the cerebellum. However, at 48 h post-dosing when cerebellar swelling and granule cell necrosis were marked, T2WI and DWI hyperintensities were observed in the cerebellum. Therefore, under the conditions of this study, MRI was not able to detect abnormalities in the cerebellum prior to the onset of the clinical signs of neurotoxicity or at the time of early histological changes. T2WI also suggested a marked increase in the amount of fluid in the ventricular system of rats 37 and 48 h after dosing; fluid accumulation was observed in all animals studied whether or not necrosis was detected. The occurrence of T2WI hyperintensity in the forebrain lead us to discover a new lesion in the habenular nucleus.

Bilateral ureteric obstruction following vaginal hysterectomy: oedema of the bladder can be a rare cause

Known causes of bilateral ureteric obstruction following vaginal hysterectomy and vaginal wall repair are accidental bilateral ureteric ligation and kinking of the ureters. A case of bilateral ureteral obstruction due to bladder wall oedema is presented. A cause for this extreme oedematous reaction was not found. Post-renal obstruction does not necessarily result in dilatation of the ureters, therefore ultrasound cannot always be used to exclude a post-renal obstruction.

Neuroprotection afforded by MK-801 against l-2-chloropropionic acid-induced cerebellar granule cell necrosis in the rat

Administration of a single oral dose of 750 mg/kg l-2-chloropropionic acid (L-CPA) to rats produces marked necrosis to the granule cell layer of the cerebellum by 48 h after dosing. Associated with the neuropathology the rats show locomotor impairment and a loss of body weight and a significant increase in cerebellar water and sodium content, indicating an oedematous reaction. Cerebellar aspartate and glutamate concentrations were reduced, while glycine and glutamine concentrations were increased after this treatment. Administration of the N-methyl-d-aspartate (NMDA) receptor channel antagonist (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), 30 min prior to L-CPA at a dose of 0.5, 1 or 5 mg/kg i.p. prevented the necrosis to the granule cell layer of the cerebellum and the signs of motor incoordination. Similarly there was no loss in cerebellar aspartate or glutamate concentration or increase in water or sodium content. Prior treatment with MK-801 at 0.1 mg/kg did not afford protection against the neurotoxicity. Post-treatment with 1 mg/kg MK-801 up to 1 h after administering L-CPA afforded complete neuroprotection, however if delayed until 2 or 6 h it gave only partial protection, and after 12 h it gave no protection. Administration of MK-801 alone at 5 mg/kg i.p., did not alter water content, sodium concentration, aspartate or glutamate concentrations in the cerebellum. In conclusion, we have shown that MK-801 given prior to and 1 h after L-CPA can afford complete neuroprotection, suggesting that a sub-population of NMDA receptors located on granule cells in cerebellum play a key role in mediating the selective toxicity of this chemical to the rat cerebellum.

Acute paw oedema formation induced by ATP: re-evaluation of the mechanisms involved.

ATP-induced inflammation was investigated using subplantar injection in the mouse hind paw. The order of efficacy of purinoceptor agonists for inducing paw oedema (30 nmol per paw) was ATP = alpha, beta-methylene ATP = 2-methylthio ATP > adenosine > UTP > ADP > AMP. Diadenosine polyphosphates effectively induced paw oedema formation with an order of efficacy of: P1,P4-di(adenosine-5')tetraphosphate = P1,P5-di(adenosine-5')-pentaphosphate = P1,P6-di(adenosine-5')hexaphosphate >>ATP = P1,P3-di(adenosine-5')triphosphate > P1,P2-di(adenosine-5')pyrophosphate. Systemic administration of P2-purinoceptor antagonists (30-100 mu mol/kg), suramin, 4,4'-diisothiocyanatostilbene-2,2'-disulphonate, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid and cibacron blue, reduced the intensity of ATP-induced oedema. At 30 mu mol/kg 8-(p-sulfophenyl)theophylline (non-selective adenosine receptor antagonist), 3,7-dimethyl-1,1-propargylxanthine (adenosine A2 receptor antagonist), triprolidine (histamine H1 receptor antagonist), ranitidine (histamine H2 receptor antagonist) and ketanserin (5-hydroxytryptamine 5-HT2 receptor antagonist), but neither 8-cyclopentyl-1,3-dipropylxanthine (adenosine A1 receptor antagonist), nor indomethacin (cyclooxygenase inhibitor) inhibited the ATP-induced swelling. Topical (100 nmol per paw), but not systemic (100 mu mol/kg) administration of NG-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor) reduced the intensity of the ATP-induced paw oedema. These results show that ATP can induce an inflammatory oedematous reaction and contribute to our understanding of the underlying mechanisms.

The biochemical and pathological changes produced by the intratracheal instillation of certain components of zinc-hexachloroethane smoke

Zinc chloride which is formed by igniting a mixture of zinc oxide and hexachloroethane in the production of white smokes has been shown to produce oedema when given to rats as a single instillation. The oedematous reaction, as assessed by hispathology and measurements of alveolar surface protein in lavage fluid, is variable, dose-dependent, and maximal at 3 days but at sub-lethal doses it regresses after 7 days. The parent compound, zinc oxide, does not produce these effects. In some animals there is evidence of a fibrogenic response at 7 days post-exposure although it is currently unknown whether or not this effect is progressive.

Colloidal carbon blocks oestrogen-induced migration of eosinophils to the uterus and the uterine water imbibition response.

Oestrogen induces a migration of eosinophil leukocytes to the uterus where, it is suggested, these cells mediate several responses to hormone stimulation. To investigate the mechanism of the recognition of the uterus by the eosinophils, the present study describes the effect of a blockade of the rat reticulo-endothelial system with colloidal carbon on oestrogen-induced uterine eosinophilia, and other responses to oestrogen stimulation that, it has been suggested, are mediated by eosinophils. In the absence of oestrogen colloidal carbon induced an increase in the number of eosinophils in mesometrium but not in endometrium with myometrium, and a slight oedematous reaction in deep endometrium. Colloidal carbon abolished the oestrogen-induced increase in the number of eosinophils in endometrium with myometrium and drastically decreased the oestrogen-induced increase in uterine wet weight and the endometrial oedematous responses 6 h after the administration of oestrogen. The present results agree with the hypothesis that most uterine water imbibition is mediated by eosinophils and suggest a possible mechanism for the interaction of colloidal carbon with eosinophil migration to the uterus.

Quantitative assessment of irritation in the mouse skin test

Intracutaneous injection of aqueous solutions of topically irritant substances into the skin of juvenile mice creates a persisting oedema, the strength of which can be assessed by the number of wrinkles formed on reefing the skin at the site of injection. An algorithm is used to transform the number of wrinkles, recorded just before and 2.5 and 6 hr after the injection, into the intensity of the oedematous reaction. This quantity, which does not depend on subjective assessments graded on an arbitrary scale, is reproducible and has been judged to be relevant to the prediction of irritancy likely to arise from accidental contact of substances with mucous membranes.

Effect of progesterone on the non-genomic response to oestrogen in the rat.

Different effects of oestrogen are mediated separately, by independent mechanisms of action. Accordingly, it has been shown that it is possible to dissociate these effects under various conditions which stimulate or inhibit responses selectively. The present study describes the action of progesterone on non-genomic responses to oestrogen stimulation which, it has been suggested, are mediated by eosinophils. Oestrogen induced an increase in the number of eosinophils in the rat uterus, an increase in uterine wet weight and oedema of deep endometrial stroma (measured as decrease in cellular density). Progesterone induced a slight oedematous reaction in superficial endometrial stroma but did not induce uterine eosinophilia. Progesterone pretreatment of oestrogen-treated rats did not block oestrogen-induced uterine eosinophilia and oedema but induced an increase in the degranulation of uterine eosinophils. Therefore the number of eosinophils decreased without any change in the uterine oedema induced after 6h of oestrogen action. The results corroborate previously published evidence of a dissociation of the action of oestrogen in independent groups of responses. Progesterone, a known blocker of some oestrogenic responses, did not block the effects mediated by eosinophils at 6h after oestrogen administration; any change in these effects at later times can be explained by an earlier eosinophil degranulation under the action of progesterone.

The quantitative assessment of topical irritancy and its application to unphysiological pH-values.

Injection of aqueous solutions of topically irritant substances intracutaneously into the skin of juvenile white mice creates a persisting oedema which can be assessed by the number of wrinkles formed upon reefing the skin at the site of injection. An algorithm is presented which transforms the number of wrinkles recorded just before as well as 2.5 h and 6 h after injection into the intensity of the oedematous reaction. The results obtained with a collective of about 10 mice per solution to be tested are reliable and reproducible; they conform to dose-response relations and hence can serve for quantifying local irritancy. The method is used to investigate the effect of pH, and a general model is developed describing the local irritancy of unphysiological pH-values.

Histopathological appearances in primary and secondary infections with Strongyloides ratti in mice

Dawkins H. J. S., Muir G. M. & Grove D. I. 1981. Histopathological appearances in primary and secondary infections with Strongyloides ratti in mice. International Journal for Parasitology 11: 97–103. The histological appearances of the skin, lungs and small intestines of mice with primary and secondary infections with S. ratti are described. When the skins of mice with a primary infection were examined, larvae were seen scattered throughout the dermis. An inflammatory reaction of neutrophils and eosinophils was first noted around larvae 12 h after infection. By 48 h, mononuclear cells were prominent. The intensity of the inflammatory reaction gradually increased to a maximum on the fifth day and the larvae were destroyed. Very few larvae were seen in the lungs; those observed were located in the alveolar spaces and were not surrounded by an inflammatory infiltrate. Worms in the small intestines were found mostly in the crypts of Leiberkuhn, and were probably located within the epithelial layer; there was no significant villous atrophy or cellular infiltration. Marked differences were found in the tissues of mice with secondary infections. In the skin, oedema and neutrophils and eosinophils were seen around worms as early as 2 h after infection. By 24 h after infection, there was a mixed inflammatory infiltrate and worms were undergoing disintegration. Larvae in the lungs were surrounded by polymorphonuclear and mononuclear cells 48 h and 72 h after infection and the engulfed larvae were undergoing lysis. Only a few worms were seen in the intestines of mice with a secondary infection; the histological appearances were similar to that found in animals with primary infections. It is suggested that the rapid development of an oedematous reaction in the skins of immune mice may facilitate the entry of larvae into the bloodstream and that inflammatory cells destroy many larvae in the lungs of immune mice.

Etude de tolérances oculaire et cutanée chez le lapin, de différentes matières premières utilisées en cosmétologie, et provenant de fabrications diverses (2ème partie)

Summary Different lots of a number of oils used in cosmetics were subjected to different storage times, analysed and their effects on rabbit eye and skin were assessed following the official French methods. The scoring system diverged slightly from the official method and was described in Part I (1). All products were tested pure in the eye test without rinsing and no corneal involvement was found. Slight congestion of the iris and conjuctivae was noted. The products showing the worst (slightly irritant) score were one sample each of avocado oil and ethyl esters of turtle oil. The highest score on the primary cutaneous irritancy test (slightly irritant) was that for the volatile hydrocarbon solvents which also gave an oedematous reaction. On dilution or on open test the reactions were negligible. The repeated application test was continued only for 8 weeks (instead of 90 days) and a histological examination was carried out on treated areas at the end of this period. The oils were applied pure and in aqueous emulsion - 10% or 2% where a severe reaction was observed. Of five samples of sweet-almond oil one showed a high degree of oxidation (peroxide value 35 meq kg(-1)). This sample did not give any significant adverse reaction whereas some irritation and vesicularisation was obtained with a sample of low peroxide value stored under nitrogen. Two of the four samples of avocado oils tested showed severe irritation and vesicle formation after 6 weeks application of the pure oil although no analytical differences were found to correlate with this result. A commercial sample of the unsaponifiable fraction of avocado oil (prepared by molecular distillation) showed severe reactions in the three rabbits treated with the pure oil, the study being terminated after 5 weeks.

Catecholamines and the oedematous reaction to oestradiol in the rat uterus

The effect of catecholamines on the 4 h oedematous reaction to oestradiol in the immature rat uterus was investigated. Isoprenaline was found to augment the reaction to suboptimal doses of oestradiol (0.25-0.5 μg/kg). This effect was reversed by d,1-propranolol. Adrenaline and noradrenaline were found to inhibit the reaction to oestradiol 2 μg/kg. The effect of adrenaline was reversed by phentolamine.

Transitory impairment of vision after light head trauma in childhood.

From a group of 101 children, eleven (10.9 p.c. ranging in age from 4--12) reported transient visual disturbances such as blurred vision, grey vision or photopsias immediately after a light head trauma. As to the origin of these impediments all evidence points to the occipital areas. Oculopupillary defects or pathological nystagmus phenomena were in no case associated. The frequency of pathological EEG recording over the occipital area was statistically significant (chi-quadrat = 4.27; p less than or equal to 0.05). The pathogenetic mechanism may be explained by means of a local oedematous reaction.

Morphological changes induced in rats following prolonged exposure to stress

Prolonged exposure of male C. S. F. rats to irregular signalled footshock from which they could escape for up to 71 days produced profound morphological changes. Retardation in growth, adrenal hypertrophy associated with an increase in the zona fasciculata and zona reticularis, and changes in the microcirculation of the heart were observed. There was a significant degree of congestion and dilatation of the microcirculation which was most marked in large venules, collecting venules and veins. An increase in PAS +ve material marginated in the venous endothelium was observed also, together with a suggested increase in mast cells and presence of vacuoles in the intima-media of the coronary arterioles. No pathological changes were observed in the renal cortex and medulla or the gastric lining. The changes in the microcirculation of the heart are discussed in terms of an oedematous reaction and a histamine type leakage of the endothelial lining.

Intubation in carcinoma of the oesophagus.

Radiotherapy has a definite place in the treatment of carcinoma of the oesophagus; in a large majority of cases regression of the tumour can be obtained by this method. Though few patients survive five years after treatment, its palliative value is evident by the number of patients who avoid terminal gastrostomy. Radiotherapy of advanced cases is frequently handicapped and complicated by the presence of very marked dysphagia. The benefit of radiotherapy would be greatly impaired if gastrostomy were to be performed before or during treatment, which is why intubation in the manner and in the circumstances described, increases the scope of radiation therapy in this field. In undernourished patients suffering from complete dysphagia of several days duration, intubation enables the patient to be prepared for radiation treatment: it is also useful in cases of dysphagia caused by congestive or oedematous reaction to radiation, occurring frequently after the first week of treatment. Obstructive symptoms caused by...