Background Zygomycosis is an increasingly emerging life-threatening infection. There is no single comprehensive literature review that describes the epidemiology and outcome of this disease. Methods We reviewed reports of zygomycosis in the English-language literature since 1885 and analyzed 929 eligible cases. We included in the database only those cases for which the underlying condition, the pattern of infection, the surgical and antifungal treatments, and survival were described. Results The mean age of patients was 38.8 years; 65% were male. The prevalence and overall mortality were 36% and 44%, respectively, for diabetes; 19% and 35%, respectively, for no underlying condition; and 17% and 66%, respectively, for malignancy. The most common types of infection were sinus (39%), pulmonary (24%), and cutaneous (19%). Dissemination developed in 23% of cases. Mortality varied with the site of infection: 96% of patients with disseminated disease died, 85% with gastrointestinal infection died, and 76% with pulmonary infection died. The majority of patients with malignancy (92 [60%] of 154) had pulmonary disease, whereas the majority of patients with diabetes (222 [66%] of 337) had sinus disease. Rhinocerebral disease was seen more frequently in patients with diabetes (145 [33%] of 337), compared with patients with malignancy (6 [4%] of 154). Hematogenous dissemination to skin was rare; however, 78 (44%) of 176 cutaneous infections were complicated by deep extension or dissemination. Survival was 3% (8 of 241 patients) for cases that were not treated, 61% (324 of 532) for cases treated with amphotericin B deoxycholate, 57% (51 of 90) for cases treated with surgery alone, and 70% (328 of 470) for cases treated with antifungal therapy and surgery. By multivariate analysis, infection due to Cunninghamella species and disseminated disease were independently associated with increased rates of death (odds ratios, 2.78 and 11.2, respectively). Conclusions Outcome from zygomycosis varies as a function of the underlying condition, site of infection, and use of antifungal therapy.

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Epidemiology and Outcome of Zygomycosis: A Review of 929 Reported Cases

Drug-induced hepatotoxicity.

Advancing age is characterized by impairment in the function of the many regulatory processes that provide functional integration between cells and organs. Therefore, there may be a failure to maintain homeostasis under conditions of physiological stress. The reduced homeostatic ability affects different regulatory systems in different subjects, thus explaining at least partly the increased interindividual variability occurring as people get older. Important pharmacokinetic and pharmacodynamic changes occur with advancing age. Pharmacokinetic changes include a reduction in renal and hepatic clearance and an increase in volume of distribution of lipid soluble drugs (hence prolongation of elimination half-life) whereas pharmacodynamic changes involve altered (usually increased) sensitivity to several classes of drugs such as anticoagulants, cardiovascular and psychotropic drugs. This review focuses on the main age-related physiological changes affecting different organ systems and their implications for pharmacokinetics and pharmacodynamics of drugs.

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Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications

Objective: To quantify the effects of smoke-free workplaces on smoking in employees and compare these effects to those achieved through tax increases. Design: Systematic review with a random effects meta-analysis. Study selection: 26 studies on the effects of smoke-free workplaces Setting: Workplaces in the United States, Australia, Canada, and Germany Participants: Employees in unrestricted and totally smoke-free workplaces Main outcome measures: Daily cigarette consumption (per smoker and per employee) and smoking prevalence Results: Totally smoke-free workplaces are associated with reductions in prevalence of smoking of 3.8% (95% confidence interval 2.8% to 4.7%) and 3.1 (2.4 to 3.8) fewer cigarettes smoked per day per continuing smoker. Combination of the effects of reduced prevalence and lower consumption per continuing smoker yields a mean reduction of 1.3 cigarettes per day per employee, which corresponds to a relative reduction of 29%. To achieve similar reductions the tax on a pack of cigarettes would have to increase from $0.76 to $3.05 (€0.78 to €3.14) in the United States and from £3.44 to £6.59 (€5.32 to €10.20) in the United Kingdom. If all workplacesbecame smoke-free, consumption per capita in the entire population would drop by 4.5% in the United States and 7.6% in the United Kingdom, costing the tobacco industry $1.7 billion and £310 million annually in lost sales. To achieve similar reductions tax per pack would have to increase to $1.11 and £4.26 Conclusions: Smoke-free workplaces not only protect non-smokers from the dangers of passive smoking, they also encourage smokers to quit or to reduce consumption

https://www.bmj.com/content/bmj/325/7357/188.full.pdf

Effect of smoke-free workplaces on smoking behaviour: systematic review

Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: implications for drug delivery and activity in cancer chemotherapy.

Effect of age and gender on the activity of human hepatic CYP3A

Objective:The objective of this study was to describe health-related productivity losses in nonsmokers, former smokers, and current smokers using a large, cross-sectional database of U.S. employees.Methods:Volunteers completed the Wellness Inventory, an instrument measuring productivity losses relat

Effect of smoking status on productivity loss.

The N-demethylation of erythromycin and 6β-hydroxylation of Cortisol are both functions of the glucocorticoid-inducible CYP3A in human liver microsomes. To determine whether 6β-hydroxylation and erythromycin N-demethylation are catalyzed by similar or distinct CYP3A isoforms, erythromycin N-demethylase activity, as reflected by the recently described 14[C]-erythromycin breath test, was compared with urinary 6β-hydroxycortisol/cortisol ratios, a measure of Cortisol 6β-hydroxylase activity, in nine patients. Erythromycin N-demethylation varied fourfold and 6β-hydroxycortisol/cortisol ratios varied sevenfold among the subjects; no correlation was found between these activities (r2 = 0.065). New noninvasive tests of CYP3A strongly suggest Cortisol 6β-hydroxylation and erythromycin N-demethylation are performed by distinct CYP3A isoforms.



Clinical Pharmacology and Therapeutics (1992) 51, 18–23; doi:10.1038/clpt.1992.3

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Heterogeneity of CYP3A isoforms metabolizing erythromycin and cortisol.

Hepatic cytochrome P-4503A (CYP3A) activity in the elderly.

Allergic reactions are among the most common conditions affecting the health of workers involved in the care and use of research animals. Between 11 and 44% of the individuals working with laboratory animals report work-related allergic symptoms. Of those who become symptomatic, 4 to 22% may eventually develop occupational asthma that can persist even after exposure ceases. Allergic symptoms consist of rashes where animals are in contact with the skin, nasal congestion and sneezing, itchy eyes, and asthma (cough, wheezing, and chest tightness). The generation of immunoglobulin E (IgE) antibodies is a prerequisite for the production of allergic symptoms. The mechanism by which IgE antibodies develop is becoming clearer. The propensity to produce IgE is genetically determined, and pre-existing allergy may be a risk factor for the development of laboratory animal allergy (LAA). However, exposure to animal allergens is the major risk factor for the development of LAA. Techniques to measure the airborne concentration of laboratory animal allergens have been developed. Research on animal allergens themselves indicates that many of the mouse and rat urinary proteins belong to a family of proteins called lipocalins, which share sequence homology with antigens of the parasitic agent that causes schistosomiasis. The fact that parasite infections also trigger IgE antibody responses may account for the development of LAA in persons who have never had any previous allergy. The prevention of LAA should be a major goal of an effective health and safety program in the animal research facility, and it can be accomplished by education and training of employees, reduction of exposure (including the use of personal protective gear), and changes in facility design. Medical surveillance programs can also play a role in improving health of individuals working with laboratory research animals. Early recognition of symptoms and evidence of sensitization can lead to interventions to reduce exposure and thereby avoid the long-term health consequences of LAA.

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Gregg M. Stave

Papers

Effect of age and gender on the activity of human hepatic CYP3A

Effect of smoking status on productivity loss.

Heterogeneity of CYP3A isoforms metabolizing erythromycin and cortisol.

Hepatic cytochrome P-4503A (CYP3A) activity in the elderly.

Laboratory animal allergy: an update.