Management of severe hypercapnia post cardiac arrest with extracorporeal carbon dioxide removal.

Normocapnia is recommended in intensive care management of patients after out-of-hospital cardiac arrest. While normocapnia is usually achievable, it may be therapeutically challenging, particularly in patients with airflow obstruction. Conventional mechanical ventilation may not be adequate to provide optimal ventilation in such patients. One of the recent advances in critical care management of hypercapnia is the advent of newer, low-flow extracorporeal carbon dioxide clearance devices. These are simpler and less invasive than conventional extracorporeal devices. We report the first case of using a novel, extracorporeal carbon dioxide removal device in Australia on a patient with out-of-hospital cardiac arrest where mechanical ventilation failed to achieve normocapnia.

Australian bat lyssavirus infection: a second human case, with a long incubation period.

In December 1998, a 37-year-old Queensland woman died from a rabies-like illness, 27 months after being bitten by a flying fox (fruit bat). Molecular techniques enabled diagnosis of infection with Australian bat lyssavirus (ABL), the second human case to be recognised and the first to be acquired from a flying fox. It must be assumed that any bat in Australia could transmit ABL; anyone bitten or scratched by a bat should immediately wash the wounds thoroughly with soap and water and promptly seek medical advice.

The Irukandji syndrome. A devastating syndrome caused by a north Australian jellyfish.

BACKGROUND: The Irukandji syndrome is a group of delayed (10-40 mins, mean 30 mins) severe systemic symptoms occurring after an initial mild skin sting by small carybdeid (box) jellyfish including Carukia barnesi, known colloquially as the 'Irukandji'. Although the syndrome is well known in tropical Australian waters, the 1998-1999 season in north Queensland was notable for the unusually high number of victims with severe toxic heart failure who needed admission to intensive care facilities for more complex investigations and treatment. There have also been other severe and unusual symptoms reported this year, which leads to the conclusion that there may be more than one species of jellyfish causing the Irukandji syndrome, or a seasonal variation in the symptoms and/or severity of symptoms caused by Carukia spp. OBJECTIVE: This article describes the updated current state of information on the ecology of jellyfish causing the Irukandji syndrome, introduces the new symptoms, and discusses some treatment regimens that may be effective. Problems associated with inappropriate treatment are also discussed. DISCUSSION: To date there have been no reported deaths from Irukandji envenomation but there have been a number of patients who were probably only saved by high quality intensive care treatment. Research into the cause and treatment of this potentially devastating syndrome is hampered by lack of funding, although there are large costs to the taxpayers for retrieval and medical treatment of victims. These costs are analysed and presented.

A presumptive case of fatal Murray Valley encephalitis acquired in Alice Springs.

A presumptive case of Murray Valley Encephalitis (MVE) acquired in Alice Springs in March 1997 is reported. The patient subsequently died in Mackay. The diagnosis of Murray Valley Encephalitis was supported by the detection of flavivirus IgM in cerebrospinal fluid. Low titres of IgM specific to Murray Valley Encephalitis and Alfuy were detected in a single serum sample. The patient's travel movements indicate that his infection was acquired in the Alice Springs vicinity. This conclusion was further supported by the detection of Murray Valley Encephalitis activity in sentinel animals in the area and by the presence of large numbers of the principal mosquito vector of Murray Valley Encephalitis in the Northern Territory.

A systematic evaluation of mechanisms in chronic cough.

We tested the hypothesis that hyperresponsiveness of the upper airway (UAHR) is present in patients with chronic cough of diverse etiology. We determined the frequency of bronchial hyperresponsiveness (BHR), hyperresponsiveness of the upper airway, sputum eosinophilia, pulmonary aspiration, and psychological symptoms in adults with chronic cough. Consecutive adults (n = 30) presenting to a tertiary referral clinic with chronic cough were compared with a group of 20 asymptomatic adults. Measurements included histamine provocation testing with measurement of flow volume curves to determine inspiratory and expiratory airflow obstruction; hypertonic saline induced sputum for analysis of eosinophils, mast cells and lipid-laden macrophages; and a validated psychological symptom questionnaire. Symptomatic rhinitis and gastroesophageal reflux were common causes of chronic cough. BHR occurred in seven patients (23%) and in no control subjects (p < 0.05). UAHR occurred in 40% of patients with cough and in four (20%) control subjects (p > 0.05). Eosinophils were present in the sputum of more patients with cough than control subjects (50% versus 19%; p < 0.05). High degrees of eosinophilia were present in six patients with cough, including three without BHR. No subject had significant lipid-laden macrophages. There was greater somatization in patients with chronic cough; ten subjects scored in the clinically significant range (p < 0.05). Abnormalities in one or more of these tests were 7.67-fold (95% CI 1.83-34.52) more likely to occur in cough patients than control subjects. We conclude that chronic cough is a nonspecific symptom that is associated with several apparently unrelated mechanisms. These include UAHR, somatization, BHR, and eosinophilic bronchitis. UAHR cannot be implicated as a single unifying mechanism. These findings emphasize the need to systematically evaluate several different causes of cough in patients who present with chronic cough.

A kinetic model for the action of the enzyme activated irreversible inhibitor 4-amino-5-hexynoic acid in vivo.

The extent of inactivation of three aminotransferases by the enzyme activated inhibitor 4-amino-hex-5-ynoate (acetylenic-GABA) increased with increasing dose in an exponential fashion. Theoretical treatment of the data allowed an estimate of the effective concentration of the drug at its site of action to be made and it was apparent that any rises in substrate concentration produced by the inactivation did not protect the enzyme significantly. Altered diet produced distinct changes in the extent of inactivation of aspartate aminotransferase, but not with ornithine aminotransferase. Cysteine sulphinate, a substrate only of aspartate aminotransferase, also affected the inactivation of ornithine aminotransferase, suggesting that secondary metabolic effects were responsible.

A low-molecular-weight inhibitor of the neutral proteinase from rat intestinal smooth muscle.

1. Rat intestinal smooth muscle was shown to contain endogenous inhibitory activity towards the neutral trypsin-like muscle proteinase described previously [Beynon & Kay (1978) Biochem. J. 173, 291--298]. 2. Comtamination of the muscle tissue by mucosal, blood and pancreatic inhibitors was shown to be unlikely. 3. The inhibitory activity was resolved into high- and low-molecular-weight components. 4. The low-molecular-weight component was purified to homogeneity. It has a molecular weight of approx. 9000 and was stable over the pH range 3--11. 5. It inhibited the muscle proteinase competitively (Ki congruent to t microM), but had no effect on any of the other proteinases tested. 6. Leupeptin also inhibited the muscle proteinase competitively (Ki congruent to 0.3 microM), whereas the low-molecular weight proteins gastrin, glucagon and insulin B-chain had very little effect. 7. A role for a weakly binding inhibitor in modulating the influence of the neutral proteinase on intracellular protein degradation is considered.

The susceptibility of muscle phosphorylases a and b to digestion by a neutral proteinase from rat intestinal muscle. Comparison with the effects produced by pancreatic trypsin and chymotrypsin.

1. Phosphorylase b was inactivated three times more rapidly than phosphorylase a by a neutral, trypsin-like proteinase from rat intestinal muscle. Digestion of phosphorylase a produced a modified form which was deactivated by AMP. Removal of the pyridoxal phosphate cofactor increased the rate of inactivation of the b form by about 3-fold but the subceptibility of apophosphorylase a was no different from the holo form. 2. The extent of proteolysis of both holoenzyme forms, as guaged by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, was limited and similar digestion patterns were obtained in both cases. 3. With (32)P-labelled phosphorylase a as substrate, the initial event in the inactivation was the release of a trichloroacetic acid-soluble peptide from the N-terminus of the enzyme, leaving the original 100000 subunit form essentially unchanged. Subsequent proteolysis was restricted, producing derivatives of mol.wt. 85000, 70000 and 65000, none of which contained any radioactive label. 4. By treatment of inactivated phosphorylase b with carboxypeptidase B, it was shown that the intestinal muscle proteinase had cleaved approximately 3 -Lys-X and 3 -Arg-X bonds in the polypeptide. 5. The protective effects of various allosteric modulators of phosphorylase on the inactivation of the a and b forms were generally in agreement with the known roles of the modifiers. Glucose increased the susceptibility of phosphorylase a. 6. Inactivation of phosphorylase b by trypsin and chymotrypsin also resulted in limited proteolysis but, in both cases, the digestion patterns obtained on sodium dodecyl sulphate/polyacrylamide gels were different from each other and from the pattern obtained with the intestinal muscle proteinase. 7. Inactivation of phosphorylase b by the muscle proteinase is about 100 times more rapid than the effects produced by trypsin or chymotrypsin when the activities are compared on an equimolar basis. 8. Consideration is given to regulation of the rate of enzyme degradation intracellularly by modulation of the conformation and susceptibility of the enzyme via factors such as covalent modification, allosteric ligands and state of aggregation.

The susceptibility of glycogen phosphorylase to inactivation by endogenous and exogenous proteases.

Phosphorylases a and b were inactivated very rapidly by a neutral, trypsin-like protease from rat intestinal muscle. With 32P-phosphorylase a as substrate, it was shown that the initial event in the inactivation was the release of a small, phosphopeptide from the N-terminus of the enzyme, leaving the original 100,000 subunit form virtually unchanged. Subsequent proteolysis was very limited, producing 85, 70 and 65,000 mol. wt. derivatives. The effects of several allosteric modulators of phosphorylase on the rates of inactivation of the two enzymes were studied. Removal of the pyridoxal phosphate cofactor from phosphorylase increased the susceptibility of the b form by three fold while the a form was unaffected. By comparison of these effects with those obtained from digestion with trypsin and chymotrypsin, it is concluded that the intestinal muscle protease has a markedly enhanced ability for inactivating enzymes in their native conformation. Assuming that this property is reflected in vivo, a possible role such neutral proteases in initiating protein degradation is advanced.

IgE-mediated anaphylactic bronchoconstriction in the guinea pig and the effect of disodium cromoglycate.

Using guinea pigs, the development of anaphylactic hypersensitivity with time after Trichinella spiralis infection has been studied, the response being assessed in terms of bronchoconstriction at 5, 12, 19 and 26 days after infection. In addition, the susceptibility of these reactions to treatment with disodium cromoglycate (DSCG) has been determined. At 12 days after infection, DSCG significantly reduced the severity of anaphylactic bronchoconstriction, suggesting that IgE competes with IgG1 antibody for sensitisation sites in the lung.