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Biomedical subjects

M J Muller

Publications and source records attributed to M J Muller.

At least 55 records · Page 3Linked to original sources

Ascariasis pneumonitis: a potentially fatal complication in smoke inhalation injury.

Ascaris pneumonitis in areas of endemic infestation is considered a benign condition. Smoke inhalation with any burn injury can be potentially fatal. A heavy infestation of Ascaris could further exacerbate the smoke-induced lung injury. After ingested eggs hatch in the small intestine, the larvae penetrate the mucosa and invade the blood stream and are then carried to the lungs. The larvae break out into the aveolar spaces as they are too large to cross the capillary bed and are carried up the bronchial tree and eventually swallowed. This study describes three cases of Ascaris infection in thermally injured children. While the burns were < 30 per cent total body surface area, two patients who were injured in the same fire had a further complication of smoke inhalation which necessitated sophisticated therapy in order to promote survival. All patients were treated initially with Vermox. The one patient without smoke inhalation did not develop ascariasis pneumonitis even with positive stool samples and was discharged with no complications, whereas the two with smoke inhalation developed severe pneumonitis. One patient was placed on ECMO and did not receive a full course of the Vermox treatment. This patient died after several weeks of ECMO treatment. The third patient received a full course of Vermox, slowly recovered, and went home. Supportive therapy only is recommended during the lung migration phase of the Ascaris lifecycle. We feel that continuation of chemotherapy (Vermox) would have been beneficial in the fatal case based on the survival of the second patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

ATP inhibits the synaptic release of acetylcholine in submucosal neurons.

Previously, we have shown that adenosine inhibits release of acetylcholine (ACh) by acting at A1 presynaptic receptors in guinea pig submucosal synapses. In this study, intracellular recordings were made to investigate the actions of ATP and some analogs on the synaptic release of ACh. Superfusion of these substances decreased the amplitude and duration of electrically induced fast excitatory postsynaptic potentials (EP-SPs) in about 90% of the tested neurons. ATP (0.1-30 microM) effects were concentration dependent with an EC50 of 1.4 microM. ADP, AMP and ATP-gamma-S mimicked ATP inhibitory effects and were equally potent and efficacious. beta,gamma-Methylene-ATP seemed to act as a partial agonist, causing less than 50% of the inhibition obtained with ATP. 2-Methyl-thio-ATP was only active at the highest concentration tested whereas alpha,beta-methylene-ATP and UTP were inactive (0.3-30 microM). ATP-gamma-S did not alter depolarizations induced by exogenous application of ACh, indicating that ATP analogs inhibit EPSPs by acting at a presynaptic site. Although the EC50 values were similar for ATP and adenosine, the maximum responses (76 +/- 4.5% and 40 +/- 1.6%) were different. Adenosine deaminase (which inactivates adenosine) and alpha,beta-methylene-ADP (an ecto-5'-nucleotidase inhibitor) did not alter ATP-induced inhibition of these EPSPs. Inhibition of EPSPs by 30 microM adenosine (maximal concentration) and 1 microM ATP (submaximal concentration) were additive. Suramin or reactive blue 2 (30 microM), antagonists of ATP actions in several tissues, did not modify the effects of ATP on the fast EPSPs. 8-Cyclopentyltheophylline inhibited, in a competitive manner, these ATP inhibitory effects. In conclusion, ATP inhibits synaptic release of ACh by acting at receptors similar to those previously identified as P3-purinoceptors.

Acetylcholine↗

Adenosine A1 receptors are not involved in contraction of canine gastric muscularis mucosae by adenosine analogues.

In vitro contractility studies were conducted in canine gastric muscularis mucosae muscle strips with the adenosine analogues 2-chloroadenosine (CIAD), 5'-N-ethylcarboxamidoadenosine (NECA), 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), R-N6-(2-phenylisopropyl)adenosine (R-PIA), S-PIA, N6-cyclohexyladenosine (CHA) and (2-p-carboxyethyl)phenylamino-5'-N-carboxamidoadenosine (CGS21680) as well as the A1-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). Adenosine analogues contracted the muscle strips with the following rank order of potency: CPCA > NECA > CIAD > R-PIA > CHA > S-PIA > CGS21680. CPCA, R-PIA, and CHA were partial agonists. At a concentration selective for adenosine A1 receptors (50 nM), DPCPX did not alter the concentration-response curves to CIAD or CHA. However, at higher concentrations (1-10 microM), DPCPX antagonized CIAD-mediated contractions in a competitive manner (pA2 = 6.96; slope = 0.93). CIAD-mediated contraction was not altered by treatment of the muscle strips with tetrodotoxin (1 microgram/ml) or mepyramine (1 microM). Our results indicate that adenosine A1 receptors, nerves or mast cells are not involved in contraction of canine gastric muscularis mucosae by adenosine analogues.

2-Chloroadenosine↗

Electric iron contact burns in an Australian paediatric population.

Accidental burn injury is common among children. Contact burns are the second most frequent cause of burns in children and electric iron contact burns constitute a substantial proportion of this group. A prospective analysis of electric iron burns presenting from 1988 to 1991 was conducted. The 38 iron burns treated during this period represented 19% of contact burns treated. The mean age of injury was 19 months. The male to female ratio was 1.1:1 and 80% involved the upper limb. Twenty-five per cent required operation. All burns occurred in the child's own home with the majority (74%) occurring in the central living areas while the child was supervised (45%). The child was most likely to be injured by touching the iron directly or pulling the cord. A substantial number of burns occurred even after the iron was switched off. Education should be directed towards the caregivers of young children emphasizing the need to use and store irons in areas to which children do not have free access. Powerpoints should be placed so that children cannot reach the cord. Manufacturers should provide insulated pads in which to store the iron and a retracting cord to help prevent the cord being within a child's reach.

Accidents, Home↗

Nutrient support of the healing wound.

Wound healing is a series of complex physicochemical interactions that require various micronutrients at every step. In the critically ill or severely injured patient, wound healing is impaired by the protein-catabolic, hypermetabolic response to stress. The hypothalamus responds to cytokine stimulation by increasing the thermoregulatory set-point and by augmenting elaboration of stress hormones (catecholamines, cortisol, and glucagon). In turn, the stress hormones induce thermogenic futile substrate cycling, lipolysis, and proteolysis. Increased glucose production results at the expense of skeletal muscle degradation, producing amino acid substrate for hepatic gluconeogenesis. Nutritional support of the hypermetabolic state is an essential part of ensuring efficient wound healing in these patients. Protein catabolism cannot be reversed by increased amino acid availability alone, due partly to a defect in amino acid transport. This defect can be reversed by anabolic agents, such as growth hormone and insulin-like growth factor-1. Growth hormone treatment dramatically improves wound healing in severely burned children. Supplementation with protein and vitamins, specifically arginine and vitamins A, B, and C, provides optimum nutrient support of the healing wound.

Adult↗

H1 contractile and H2 relaxant receptors in canine gastric muscularis mucosae.

Histamine had two effects on the contractility of canine gastric muscularis mucosae in vitro: relaxation at or below 10 microM and contraction at higher concentrations. Selective agonists and antagonists were used to test the possibility that these effects were mediated by different receptor subtypes. The H1-selective agonist 2-pyridylethylamine (2-PEA) and the H2-selective agonist dimaprit contracted and relaxed this muscle, respectively, while the H3-selective agonist R-alpha-methylhistamine had no effect. The H1- and H2-selective antagonists mepyramine and ranitidine selectively blocked 2-PEA-mediated contractions and dimaprit-mediated relaxations, respectively. Agonist responses, were unaltered by tetrodotoxin, suggesting a site of action other than nerves. Our results indicate that canine gastric corpus muscularis mucosae possesses both contractile H1 and relaxant H2 receptors.

Animals↗

Control of pepsinogen synthesis and secretion.

The heterogeneous group of proteinases known as pepsinogens are synthesized, stored, and upon appropriate stimulation released from gastric mucosal chief cells. Under the acidic conditions of the lumen of the stomach, the proenzymes, pepsinogens, are converted to "pepsin", which plays an important physiologic role as a digestive enzyme. The potential roles for pepsin in upper gastrointestinal diseases such as gastric or duodenal ulcer and gastroesophageal reflux disease along with the recent development of in vitro gastric gland and isolated chief cell preparations have renewed interest in the study of the control of pepsinogen synthesis and secretion. In this article the authors briefly summarize current knowledge of the biology of pepsinogens and emphasize more recent findings concerning the control of the chief cell, which is related to the synthesis and secretion of pepsinogens in vitro.

Animals↗

Altered smooth muscle contraction and sodium pump activity in the inflamed rat intestine.

We examined changes in membrane function underlying the increased contractility of jejunal longitudinal muscle to carbachol in rats infected 6 days previously with Trichinella spiralis. Muscarinic receptor characteristics were examined in particulate fractions using [N-methyl-3H]scopolamine (NMS). There was a significant reduction in the total number of binding sites on muscle from infected rats, but the affinity for NMS was unchanged. Similarly, in competition studies, the binding of carbachol to high or low affinity sites was not significantly different in tissue from control or infected rats. However, we observed an 89% suppression of the activity of K+ -stimulated ouabain-sensitive p-nitrophenylphosphatase (pNPPase), an enzyme marker for the Na+ -K+ pump, in plasma membranes from infected compared with control rats. Similar results were obtained in 86Rb uptake studies. In contractility studies, evidence for the electrogenicity of the Na+ -K+ pump was obtained by demonstrating that pump activation by K+, Rb+, or Cs+ was associated with tissue relaxation with a rank order of potency that was identical to that for stimulation of pNPPase activity by these ions. Conversely, pump inhibition by vanadate increased tone and abolished phasic contractions in muscle from control or infected rats. This was accompanied by an increased response to carbachol in muscle from control but not infected rats. In addition, pump inhibition by removing extracellular K increased tone in control tissue but decreased tone in muscle from T. spiralis-infected rats, presumably because of preexisting pump suppression. These results are consistent with the hypothesis that suppression of electrogenic Na-pump activity contributes to the increased contractility of jejunal muscle in rats infected with T. spiralis.

Animals↗

Receptors for tachykinins in canine intestine circular muscle.

125I-Tyr8-substance P binding was examined in a plasma membrane enriched fraction from the circular muscle of canine small intestine. The binding was quick in onset, reversible and saturable to a single high affinity binding site; KD and maximum receptor concentration were 0.50 = 0.06 nM and 742 +/- 173 fmol/mg of protein, respectively. KD values from kinetic and saturation studies were in agreement. The rank order of potency of the tachykinins and related compounds in displacing this binding was consistent with that of a neurokinin (NK)-P (NK-1) type binding site. 125I-eledoisin did not bind specifically to these membranes and eledoisin was relatively ineffective in displacing the 125I-Tyr8 substance P. Kassinin was totally ineffective. Based on relative agonist potencies, the tachykinins appeared to contract the circular muscle of canine small intestine in vitro by a mechanism which also could be considered to be a NK-P (NK-1) type receptor. However, a comparison of data obtained by these two techniques suggests that the NK-P (NK-1) type binding site and the receptor(s) responsible for contractile responses are not identical. There were discrepancies in relative orders of potency and in absolute potencies. The simplest explanation is that there is also an NK-A (NK-2) receptor which is functional but not labeled by our ligands. Possible reasons for these discrepancies are discussed.

Animals↗

Vectors of bluetongue virus in Australia.

Two of the 5 serotypes of bluetongue virus (BTV) known from Australia have been isolated from field collected insects. Serotype 20 was isolated in 1975 from a mixed pool of 214 insects containing several Culicoides species. Serotype 1 has been isolated from C. (Avaritia) fulvus Sen & Das Gupta collected at Beatrice Hill in the Northern Territory and from C. (Avaritia) brevitarsis Kieffer collected at Peachester in southeast Queensland. All other isolates of bluetongue (BT) group viruses have been made from sentinel cattle. An additional 2 species of the subgenus Avaritia, C. wadai Kitaoka and C. actoni Smith, 1 species of the subgenus Culicoides, C. peregrinus Kieffer and 1 species of the Schultzei group, C. oxystoma Kieffer have been infected in the laboratory. Serotype 20 was transmitted from sheep to sheep by C. fulvus and serotype 1 by C. fulvus and C. actoni. The infection rates established for Culicoides fed on sheep infected with serotype 20 were C. fulvus 62%; C. wadai 11%; C. actoni 2% and C. brevitarsis 0.3%. All species of insects successfully infected are widely distributed in the Oriental region. Attempts to infect species that are restricted in range to the Australasian region have been unsuccessful. The 3 species with highest experimental infection rates: C. fulvus, C. wadai and C. actoni, are confined in Australia to areas with an annual summer rainfall in excess of 800 mm, and do not penetrate to the drier areas where sheep are commercially husbanded. C. brevitarsis is the vector responsible for transmission in the coastal dairying areas, and although it does occur where sheep are reared, it is an inefficient vector. It breeds in discrete cow dung pats on pasture and is more closely associated with cattle than with sheep when the 2 hosts occur together. More than 1 species of Culicoides is responsible for the transmission of BT group viruses in Australia and no BT disease of sheep has been recorded because the more efficient vector species are not present in sheep rearing areas.

Animals↗