Guidelines for the management of patients with invasive candidiasis and mucosal candidiasis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous guidelines published in the 15 January 2004 issue of Clinical Infectious Diseases and are intended for use by health care providers who care for patients who either have or are at risk of these infections. Since 2004, several new antifungal agents have become available, and several new studies have been published relating to the treatment of candidemia, other forms of invasive candidiasis, and mucosal disease, including oropharyngeal and esophageal candidiasis. There are also recent prospective data on the prevention of invasive candidiasis in high-risk neonates and adults and on the empiric treatment of suspected invasive candidiasis in adults. This new information is incorporated into this revised document.

https://www.easy-immune-health.com/support-files/clin_practice_guidelines_candidiasis.pdf

Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America.

This review brings you up-to-date with the hepatocyte research on: 1) in vitro-in vivo correlations of metabolism and clearance; 2) CYP enzyme induction, regulation, and cross-talk using human hepatocytes and hepatocyte-like cell lines; 3) the function and regulation of hepatic transporters and models used to elucidate their role in drug clearance; 4) mechanisms and examples of idiosyncratic and intrinsic hepatotoxicity; and 5) alternative cell systems to primary human hepatocytes. We also report pharmaceutical perspectives of these topics and compare methods and interpretations for the drug development process.

Primary Hepatocytes: Current Understanding of the Regulation of Metabolic Enzymes and Transporter Proteins, and Pharmaceutical Practice for the Use of Hepatocytes in Metabolism, Enzyme Induction, Transporter, Clearance, and Hepatotoxicity Studies

The impact of a new therapy that includes pressure-controlled inverse ratio ventilation followed by extracorporeal CO 2 removal on the survival of patients with severe ARDS was evaluated in a randomized controlled clinical trial. Computerized protocols generated around-the-clock instructions for management of arterial oxygenation to assure equivalent intensity of care for patients randomized to the new therapy limb and those randomized to the control, mechanical ventilation limb. We randomized 40 patients with severe ARDS who met the ECMO entry criteria. The main outcome measure was survival at 30 days after randomization

Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome

ObjectiveTo examine the relationship between glutamine supplementation and hospital length of stay, complication rates, and mortality in patients undergoing surgery and experiencing critical illness.Data SourcesComputerized search of electronic databases and search of personal files, abstract procee

Glutamine supplementation in serious illness: a systematic review of the evidence.

The number of intoxications with organophosphorus pesticides (OPs) is estimated at some 3,000,000 per year, and the number of deaths and casualties some 300,000 per year. OPs act primarily by inhibiting acetylcholinesterase (AChE), thereby allowing acetylcholine to accumulate at cholinergic synapses, disturbing transmission at parasympathetic nerve endings, sympathetic ganglia, neuromuscular endplates and certain CNS regions. Atropine is the mainstay of treatment of effects mediated by muscarine sensitive receptors; however, atropine is ineffective at the nicotine sensitive synapses. At both receptor types, reactivation of inhibited AChE may improve the clinical picture. The value of oximes, however, is still a matter of controversy. Enthusiastic reports of outstanding antidotal effectiveness, substantiated by laboratory findings of reactivated AChE and improved neuromuscular transmission, contrast with many reports of disappointing results. In vitro studies with human erythrocyte AChE, which is derived from the same single gene as synaptic AChE, revealed marked differences in the potency and efficacy of pralidoxime, obidoxime, HI 6 and HLo 7, the latter two oximes being considered particularly effective in nerve agent poisoning. Moreover, remarkable species differences in the susceptibility to oximes were revealed, requiring caution when animal data are extrapolated to humans. These studies impressively demonstrated that any generalisation regarding an effective oxime concentration is inappropriate. Hence, the 4 mg/L concept should be dismissed. To antagonise the toxic effects of the most frequently used OPs, pralidoxime plasma concentrations of around 80 mumol/L (13.8 mg/L pralidoxime chloride) should be attained while obidoxime plasma concentrations of 10 mumol/L (3.6 mg/L obidoxime chloride) may be sufficient. These concentrations should be maintained as long as circulating poison is expected to be present, which may require oxime therapy for up to 10 days. Various dosage regimens exist to reach this goal. The most appropriate consists of a bolus short infusion followed by a maintenance dosage. For pralidoxime chloride, a 1 g bolus over 30 minutes followed by an infusion of 0.5 g/h appears appropriate to maintain the target concentrtion of about 13 mg/L (70 kg person). For obidoxime chloride, the appropriate dosage is a 0.25 g bolus followed by an infusion of 0.75 g/24 h. These concentrations are well tolerated and keep a good portion of AChE in the active state, thereby retarding the AChE aging rate. AChE aging is particularly rapid with dimethyl phosphoryl compounds and may thwart the effective reactivation by oximes, particularly in suicidal poisoning with excessive doses. In contrast, patients with diethyl OP poisoning may particularly benefit from oxime therapy, even if no improvement is seen during the first days when the poison load is high. The low propensity to aging with diethyl OP poisoning may allow reactivation after several days, when the poison concentration drops. Rigorous testing of the benefits of oximes is only possible in randomised controlled trials with clear stratification according to the class of pesticides involved, time elapsed between exposure and treatment and severity of cholinergic symptoms on admission.

https://link.springer.com/content/pdf/10.2165%2F00139709-200322030-00004.pdf

The role of oximes in the management of organophosphorus pesticide poisoning

Glutamine dipeptide-supplemented parenteral nutrition maintains intestinal function in the critically III

Background
Voriconazole was introduced for the treatment of life-threatening fungal infections. The intravenous form includes the solvent vehicle sulphobutylether beta cyclodextrin sodium which shows an impaired clearance under intermittent dialysis therapy. This investigation aimed to determine first clinical data on sulphobutylether beta cyclodextrin sodium blood levels to verify the risk for accumulation.

/pdf/accumulation-of-the-solvent-vehicle-sulphobutylether-beta-omzbgl4avy.pdf

Accumulation of the solvent vehicle sulphobutylether beta cyclodextrin sodium in critically ill patients treated with intravenous voriconazole under renal replacement therapy

Acute organophosphate intoxication resulting from suicide attempts in 14 patients produced a series of electrophysiologic abnormalities that correlated with the clinical course. Spontaneous repetitive firing of single evoked compound muscle action potentials (CMAP) was the earliest and most sensitive indicator of the acetylcholinesterase inhibition. A decrement of evoked CMAP following repetitive nerve stimulation was the most severe abnormality. At the height of the intoxication no CMAP was evoked after the first few stimuli. The decrement-increment phenomenon occurred only at milder stages of intoxication and its features are characteristic of acetylcholinesterase inhibition. These electrophysiologic features proved to be the most useful for determining initial severity and clinical course of the acute organophosphate intoxication and differentiated this syndrome from those of myasthenia gravis, Eaton-Lambert syndrome, and botulism.

End-plate dysfunction in acute organophosphate intoxication.

Objective: Overdoses with insulin are common, and cases of hypoglycemic coma can be fatal and cause cerebral defects. However, data published on this topic are rare, consisting mostly of case reports or reports in a smallnumber of patients. The present investigation analyzes inquiries made to a regional poisons unit involving overdoses with insulin. Patients and methods: A total of 175,890 inquiries for the years 1995 2003 (until September) were evaluated. 160 inquiries were received by telephone concerning insulin overdoses, and a standardized questionnaire was sent to the physicians asking for follow-up information. The cases were analyzed in regard to etiology, type of insulin used, concomitant substances being taken by the patient, symptoms and clinical outcome. Results: Of the 160 inquiries investigated, 53.1% of the patients were female, 43.1% male and in 3.8% the sex of the patient was unknown. The average age was 44.7 years. 89.4% involved suicidal or parasuicidal cases, 5.0% were accidental overdoses and 1.9% involved cases of criminal overdose (3.7% were for other reasons). Rapidly acting insulins (57.8%) were used more commonly than long-acting formulations (42.8%). Benzodiazepines were the most frequently ingested concomitant medication (37.5%) with ethanol 15.6%, antihypertensive drugs 12.5% and antidepressants 10.0%. Most patients presented with a delay of 2 - 3 hours after insulin administration (15.0%). Almost 50% of the patients presented within the first 6 hours. According to the Poisoning Severity Score, no symptoms were observed in 16.8% of the patients, minor symptoms in 36.8%, major symptoms in 25.2% and serious symptoms in 21.3%. Information concerning the clinical outcome (75 cases) showed that a full recovery occurred in most patients (94.7%), but in 2.7% there were cerebral defects and 2.7% of the patients died. Conclusions: The etiology of overdoses with insulin was mainly deliberate self-poisoning. Physicians should take into account that long-acting insulin formulations and concomitant substances were frequently used. For overdoses with insulin, relatively high rates of serious symptoms and deaths were observed.

Epidemiological assessment of 160 cases of insulin overdose recorded in a regional poisons unit.

Large amounts and excellent viabilities of pancreatic
islets are prerequisites for recent advances in islet
transplantation Cryopreservation has been shown to enlarge
transplanted cell mass, but has been accompanied by reduced
viability In this study rat pancreatic islets were
differentiated into small (<200 µm), medium (200–400 µm) and
large (>400 µm) categories and their susceptibilities to
different freezing conditions were evaluated: concentration of
cryoprotectant (07–31 M), equilibration (15 vs 45 min, 22° C
vs on ice) and post-thaw removal of cryoprotectant (15 vs 30
min, stepwise vs one-step) The most prominent finding was a
negative correlation between islet size and viability observed
in non-frozen islets to a minor degree (r=-044) and
significantly enhanced after cryopreservation (r<-08) The
concentration of cryoprotectant showed the most significant
influence on viability affecting small, medium and large islets
Different techniques of equilibration with the cryoprotectant
resulted in significant changes of islet viability of medium
islets, whereas small and large islets were unaffected For
different techniques of removal of the cryoprotectant, no
significant influence on viabilities was found We conclude that
large islets represented a highly susceptible population
concerning damage due to cryopreservation

L. S. Weilemann

Papers

Glutamine dipeptide-supplemented parenteral nutrition maintains intestinal function in the critically III

Accumulation of the solvent vehicle sulphobutylether beta cyclodextrin sodium in critically ill patients treated with intravenous voriconazole under renal replacement therapy

End-plate dysfunction in acute organophosphate intoxication.

Epidemiological assessment of 160 cases of insulin overdose recorded in a regional poisons unit.

Size of pancreatic islets of Langerhans: a key parameter for viability after cryopreservation.