Epidemiology of trauma: military experience

Battle injuries sustained in conventional warfare are more likely to be lethal than are injuries sustained by civilians. Depending on the tactical situation, mortality may range from 20% to more than 80% of all casualties. The American experience indicates that about 90% of the total mortality occurs on the battlefield. Such casualties, those classified as killed in action, die before reaching medical care. More than 90% of all battle injuries (morbidity) are caused by penetrating missiles. Exsanguination from wounds of the heart/great vessels and penetrating/perforating wounds of the skull cause the majority of battlefield deaths. The frequency distribution of injury severity appears to be bimodal. A large peak occurs at low injury severity and indicates a population of casualties with relatively benign soft tissue wounds. A smaller peak at high injury severity represents those killed in action.     

Role of glutathione and its associated enzymes in multidrug-resistant human myeloma cells

Multidrug resistance (MDR) is a phenomenon associated with the emergence of simultaneous cross-resistance to the cytotoxic action of a wide variety of structurally and functionally unrelated antineoplastic agents. The present study was undertaken to determine if 8226 human myeloma cells possessing the MDR phenotype had an increased ability to resist the intercalating drug doxorubicin (DOX) via glutathione-based detoxification systems. Glutathione S-transferase (GST) was isolated by affinity chromatography, and the enzyme activity was assessed using 1-chloro-2,4-dinitrobenzene (CDNB) and glutathione (GSH) as substrates. There was no difference in overall GST activity between the sensitive and resistant cells. Using a cDNA probe (pGTSS1-2) for the human placental, anionic GST isoenzyme, no overexpression of mRNA for this isoenzyme was noted in the resistant line. When glutathione peroxidase activity (GSH-px) was assessed using either H2O2 or cumene hydroperoxide as substrate, again there was no difference in enzyme activity. Non-protein sulfhydryl (NPSH) levels were found to be elevated significantly in the resistant 8226/DOX40 subline (19.2 +/- 0.1 nmol NPSH/10(6) cells) as compared to the drug-sensitive parental subline 8226/S (11.6 +/- 1.9 nmol NPSH/10(6) cells) (P less than 0.001). In addition, when the 8226/DOX40 cells were cultured in medium without doxorubicin, there was a consistent decline in NPSH values reaching a steady state identical to that of the 8226/S cells. However, the decrease in NPSH level was not accompanied by a change in the level of doxorubicin resistance as assessed by colony-forming assays. Depletion of glutathione by D,L-buthionine-S,R-sulfoximine had no effect on doxorubicin sensitivity in either subline. Thus, it appears that GSH-based detoxification systems are not causally involved in maintaining the MDR phenotype in 8226 human myeloma cells; rather they appear to comprise an epiphenomenon associated with the resistance selection procedure.     

Therapeutic issues in transplant patients

Patients who have undergone previous organ transplantation represent a considerable therapeutic challenge to the anaesthetist. Although a transplant may have restored normal or near-normal function for that organ, the original underlying pathology often persists. In addition, undesirable effects of immunosuppressant drugs, particularly calcineurin inhibitors, may give rise to damage to other organs and organ systems. Diabetes, hyperlipidaemia and accelerated vascular and renal damage are a common feature. The majority of post-transplant patients require treatment for these phenomena. Common medications include statins, antihypertensives and sometimes prophylaxis against nosocomial infection. When managing post-transplant patients, both drugs and pathology have to be taken into account. Non-steroidal anti-inflammatory drugs pose a particular hazard.     

A survey of current prescribing practices of anti-inflammatory and urate-lowering drugs in gouty arthritis in New South Wales and Queensland

We recently have conducted a cross-sectional survey to determine the prescribing practices of rheumatologists and a random sample of general practitioners in New South Wales and Queensland. While in general there was agreement as to the preferred management of gout, several important differences were noted between the two groups of doctors. In particular, general practitioners were more liberal than were rheumatologists in their use of allopurinol. However, they were less likely to cover the introduction of allopurinol with anti-inflammatory agents, to titrate the dose against the serum uric acid level or to adjust the dose according to the serum creatinine level. A small number of doctors continued to use urate-lowering drugs as a routine in the treatment of entirely asymptomatic hyperuricaemia. The data indicate a continuing need to disseminate information regarding the preferred management of hyperuricaemic states.     

Admitting elderly patients to the ICU: dilemmas and solutions

Since intensive care is expensive and has limited efficacy, its use should be reserved primarily for patients with acute, reversible illnesses. Although age is related to ICU mortality, more important predictors of ICU outcome are severity of the acute illness, the admitting diagnosis, and previous health status. Thus, age should not be the sole factor considered prior to ICU transfer or the initiation or denial of resuscitative efforts. Geriatric physicians should prospectively develop individualized plans for each of their patients based upon the patients' wishes after a discussion of diagnosis, prognosis, and the likely efficacy and side effects of the available treatments.     

Functional iron deficiency, infection and systemic inflammatory response syndrome in critical illness.

To investigate the prevalence and clinical relevance of functional iron deficiency in the critically ill, we performed a prospective observational study in a university hospital general intensive care unit. We collected patient demographics, severity of illness data, haematological and biochemical variables in 51 consecutive admissions. We recorded episodes of culture-positive infection. Functional iron deficiency (FID), measured by red cell hypochromasia on flow cytometry, was present in 35% of patients at admission to intensive care. FID patients were of similar age, diagnosis, APACHE score, sequential organ failure assessment (SOFA) score, haemoglobin, serum B12, folate and ferritin to patients without FID. However, patients with FID had a prolonged intensive care stay compared with non-FID patients (P<0.001) and increased time to hospital discharge (P=0.09). Duration of intensive care stay correlated with severity of FID (r=0.33, P<0.02). Systemic inflammatory response syndrome (SIRS) was present for longer in those with FID (P<0.02). Overall mortality did not differ between groups. No difference was seen in the incidence of positive cultures between those with FID (9/18 patients) and those without FID (15/33 patients). FID was independently associated only with abnormal white blood cell count (WBC < 4 or > 11 x 10(9) x l(-1)) at admission to ICU, P=0.007, but not with positive cultures. There is a high prevalence of FID in intensive care, associated with an increased duration of stay and duration of SIRS. We have been unable to demonstrate a link with infection, either as a predisposing factor or as an acute response.     

核、膜蛋白的基因能抑制禽类流感病毒及其重组株的繁殖

对人流感病毒A/Udorn/72(H_3N_2)株与禽类流感病毒A/Mallard/NY/78/(H_2N_2)重组后的重组株分析表明,仅含禽类病毒的核蛋白(NP)或膜蛋白(M)的RNA片段的重组株,在松鼠猴的呼吸道繁殖是受限制的。另外。仅有禽类的RNAl和NS基因的重组株(Clone 12)在松鼠猴的气管内的繁殖也明显受限制,而只具有其中一个基因的Clone 9, Clone 2, 则限制就不明显。由此表明,禽类流感病毒的NP和M基因在宿主范围的繁殖限制中起主要作用,而RNAI和SN基因的结合,同样起着繁殖受限制作用。     

Effects of phenobarbital on the biliary excretion of aflatoxin P1-glucuronide and aflatoxin B1-S-glutathione in the rat

Direct h.p.l.c. analysis of bile separated at least five major water-soluble metabolites of AFB; the two most prevalent AFB metabolites were identified as AFB-S-glutathione (AFB-GSH) and AFP1-glucuronide, which accounted for 49-57% and 4-15% of total biliary AFB metabolites, respectively. In the two hours following AFB administration, phenobarbital-treated rats eliminated 50% more AFB-derived radioactivity in bile compared with controls. No qualitative differences in the profile of biliary AFB metabolites were noted between phenobarbital-treated and control rats. However, a 90% increase in the rate of excretion of AFB-GSH was found in phenobarbital-treated animals. Phenobarbital treatment had no significant effect on the amount of AFB remaining in the liver after two hours, but decreased the amount of AFB covalently bound to hepatic DNA by 55%. When individual animals from both control and phenobarbital-treated groups were considered, the correlation between the increase in excretion of AFB-GSH and the decrease in covalent binding was significant with a correlation coefficient of 0.77. This finding is consistent with the hypothesis that induction of GSH S-transferase is responsible for the anticarcinogenic effects of phenobarbital towards AFB-induced hepatocarcinogenicity, although changes in the rate of formation of aflatoxin P1 or other biotransformation pathways may also be important.