Chronic mycoses of the paranasal sinuses--value of endonasal paranasal sinus surgery

BACKGROUND: Many host factors even in immunocompetent patients may have an influence on development of a fungal diseases within the paranasal sinuses. Fungal sinusitis can occur in an acute form or more often to a chronic type of the disease. These mainly relatively asymptomatic chronic forms and further divided into a chronic noninvasive, chronic allergic, and chronic invasive disease. Endonasal microsurgery has significantly changed the management of chronic fungal sinusitis and allows adequate removal of pathologic tissue even in advanced situations. The aim of this study was to analyze the efficacy of endonasal surgery in chronic fungal sinusitis. MATERIAL AND METHODS: In a retrospective study we assessed a group of 40 patients who had endonasal surgery for chronic fungal sinusitis. Patient records, CT and MRI scans, microbiology and histology as well as the postoperative clinical follow-up including endoscopic photo documentation were evaluated over a period of 5 years. All patients underwent endonasal surgery using endoscopic techniques. The microscopic was of additional help in a few cases with extended disease and multiple dehiscences of the skull base. RESULTS: Twenty-four patients had a chronic noninvasive of fungal sinusitis and 16 patients had a chronic invasive form. All these patients underwent endonasal surgery without external incision. The fungal disease was erradicated in 39 cases, and revision surgery was required in only one case in which involvement of the contralateral side was not initially detected. in two cases scar tissue in the middle meatus was later excised but without evidence of residual fungal disease. Only in 6 cases was antifungal chemotherapy required, where the disease had spread into surrounding tissue or the patient had severe symptoms. CONCLUSIONS: Endonasal microsurgical techniques are today the appropriate approach for managing chronic fungal sinus disease even in severe cases with radiologic evidence of expansion or invasion of surrounding tissue. Additional antifungal chemotherapy is only rarely indicated, specifically when the fungal disease invades surrounding tissue.     

Report of the first case of invasive fungal sinusitis caused by Scopulariopsis acremonium: review of scopulariopsis infections

Scopulariopsis acremonium is a species of saprophytic fungus not previously reported to cause invasive disease in humans, although invasive infections from other species of Scopulariopsis have been reported and are reviewed. Deep infection with this fungus is associated with a high mortality rate. Invasive fungal sinusitis, in general, is a potentially fatal disease that typically affects immunocompromised patients, such as those receiving intensive chemotherapy or undergoing bone marrow transplantation. We report a case of invasive fungal sinusitis caused by Scopulariopsis acremonium in a patient with leukemia, who was successfully treated with amphotericin B, itraconazole, endoscopic sinus surgery, and granulocyte colony-stimulating factor.     

Thrombin inhibition by antithrombin III on the subendothelium is explained by the isoform AT beta

Rhinocerebral mucormycosis is a well-described fulminant fungal infection that typically presents acutely in patients with diabetic ketoacidosis or immunosuppression. Chronic presentations of rhinocerebral mucormycosis have also been described. In the chronic infection, the disease course is indolent and slowly progressive, often occurring over weeks to months. The authors report 2 cases of chronic rhinocerebral mucormycosis (CRM) treated at their institution and review 16 other cases reported in the English-language literature. In these cases, the median time from symptom onset to diagnosis was 7 months. The most common presenting features of CRM are ophthalmologic and include ptosis, proptosis, visual loss, and ophthalmoplegia. CRM occurs predominantly in patients with diabetes and ketoacidosis. The incidence of internal carotid artery and cavernous sinus thrombosis is higher in CRM patients than in those with the acute disease, although the overall survival rate for CRM patients is 83%. CRM is clinically distinct from chronic Entomophthorales infection.     

The changing role of village health volunteers in northeast Thailand: an ethnographic field study

Aspergillus sinusitis is an uncommon complication of advanced human immunodeficiency virus (HIV) infection. We describe 2 patients with AIDS who developed histologically proven invasive Aspergillus sinusitis. We also review the findings of 14 histologically documented and 5 probable cases of invasive Aspergillus sinusitis. The literature on the prevalence, predisposing factors, diagnosis, treatment, and prognosis of the infection is reviewed. Major risk factors for the disease are advanced AIDS, chronic sinusitis or otitis, neutropenia, use of corticosteroids and prolonged use of broad spectrum antibiotics. The most common presenting symptoms are nonspecific and include fever, local pain, and swelling. Despite the newer diagnostic and therapeutic approaches discussed herein, the infection is usually fatal in HIV-infected patients. Early diagnosis and aggressive treatment remain the only available means to improve the currently dismal prognosis of Aspergillus sinusitis.     

Invasive mold sinusitis: 17 cases in immunocompromised patients and review of the literature

A 10-year retrospective analysis of invasive mold infections in hospitalized patients was performed to characterize the epidemiology and clinical features of invasive fungal sinusitis. Seventeen cases of invasive mold sinusitis were identified. Eleven cases were caused by Aspergillus flavus, three were caused by unspecified species, and one each was caused by Aspergillus fumigatus, Rhizopus species, and Alternaria species, respectively. Fifteen patients had hematologic malignancies, and two had end-stage liver disease. The most common presenting symptom was periorbital swelling (seven patients). Sinusitis was diagnosed a median of 19 days after admission. Eight patients (47%) survived; six of these patients were treated with both amphotericin B and surgery. Postmortem examination of six patients showed evidence of disseminated disease; the brain was the most common extrapulmonary site (four patients). To our knowledge, this is the largest currently reported series on invasive mold sinusitis; our report extends the information on invasive mold sinusitis and shows that aggressive therapeutic and surgical interventions are needed to prevent rapid progression of disease in immunocompromised patients.     

Unusual manifestation of Coccidioides immitis infection

Cavitary pulmonary disease secondary to coccidioidomycosis occurs in endemic areas of the southwestern United States. Significant hemoptysis requiring pulmonary resection may develop in patients with cavitary lesions. In rare instances hemoptysis may be due to the development of a fungus ball within the cavity, and such mycetomas may contain spherule and mycelial forms of Coccidioides immitis. A patient with a documented coccidioidal cavity who had hemoptysis is described in this report. Chest radiograph revealed a fungus ball within a left lower lobe cavity. The patient underwent left lower lobectomy and recovered without complications. Examination of the resected left lower lobe disclosed a cavity containing a fungus ball comprised of mycelial and spherule forms of Coccidioides immitis. A review of the literature found three reports of biphasic growth of this condition within a coccidioidomycosis cavity and two additional cases of radiographically diagnosed coccidioidal mycetoma. Discussion of the potentially contagious nature, the medical and surgical management, and the prognosis of coccidioidal mycetoma form the basis of this report.     

Evaluation and treatment of allergic fungal sinusitis. I. Demographics and diagnosis

BACKGROUND: Few cases of allergic fungal sinusitis have been systematically evaluated to conclusively confirm working clinical, histopathologic, and serologic diagnostic criteria. OBJECTIVES: The objective of this study was to describe 67 consecutive cases of allergic fungal sinusitis, the largest number of cases yet published. METHODS: Cases from 1 practice over 8 years were evaluated with a consistent protocol, including skin testing, serum chemistries and serologies, and surgical specimen analysis. RESULTS: All patients were atopic (100 %) and had nasal polyposis (100%). They tended to be young (33.3+/-13.1 years, mean +/-SEM), immunocompetent (92 %; remaining 8 % with low quantitative immunoglobulin but normal function), have slight female preponderance (58%), have a history of hypertrophic rhinosinusitis (100%), report nasal cast production (75%), and have developed their disease in the southwestern United States. Bipolaris spicifera was the most prevalent fungus involved (67%). Total serum IgE (mean 668 IU/mL) and fungal-specific IgG were generally elevated, whereas fungal-specific precipitins and specific IgE were generally negative despite positive fungal-specific immediate hypersensitivity skin tests. CONCLUSIONS: Patients with allergic fungal sinusitis tend to have elevated total serum IgE and fungal-specific IgG at diagnosis but not fungal-specific IgE or precipitins. Histopathologic criteria for allergic fungal sinusitis diagnosis are discussed. The southwestern United States appears to be a "hot spot" for the disease, particularly caused by B spicifera.     

Association of mutations in the core promoter and precore region of hepatitis virus with fulminant and severe acute hepatitis in Japan

It was recently reported that mutations in the precore and core promoter region of hepatitis B virus (HBV) are associated with fulminant hepatitis. The aim of this study was to investigate the association of mutations in the precore and core promoter region of HBV with fulminant and severe acute hepatitis. We studied Japanese patients with acute HBV infection, including seven patients with fulminant hepatitis, 12 with severe acute hepatitis and 41 with acute self-limited hepatitis. The presence of HBV mutants was examined by using a point mutation assay to detect a G to A transition at position 1896 in the precore region and an A to T transition at position 1762 and a G to A transition at position 1764 in the core promoter region. Significant differences in the proportion of mutations in the precore or core promoter region were present between patients with fulminant hepatitis and self-limited acute hepatitis (7/7 (100%) vs 4/41 (9.8%), P<0.01) and between severe acute hepatitis and self-limited acute hepatitis (6/12 (50.0%) vs 4/41 (9.8%), P<0.01). The frequency of mutation increased proportionately with the severity of disease in patients with acute HBV infection. Fulminant hepatitis B in Japan is closely associated with mutations in the core promoter and precore gene of HBV. Point mutation assays for HBV precore and core promoter analysis may be useful to predict the outcome of liver disease in patients with acute HBV infection.     

Diagnosis and management of ischemic heart disease in the patient scheduled to undergo electroconvulsive therapy

The cardiovascular risk of electroconvulsive therapy (ECT) is a product of the stress of ECT itself and the severity and stability of coronary artery disease (CAD), as well as other cardiovascular factors. ECT itself represents a relatively low-risk procedure. Patient-specific risk can be defined by a combination of clinical evaluation and noninvasive testing, much of which is aimed at detecting the presence and staging the severity and stability of CAD. Patients at high risk of a cardiac complication include those with severe or unstable symptoms of CAD, and they should undergo extensive cardiac evaluation before ECT Patients at low risk likely need no further evaluation and can undergo ECT. Patients at intermediate risk should have careful clinical evaluation, and most likely noninvasive evaluation, which should include some form of stress testing. Medical therapy should be continued and/or maximized in all patients with CAD. It is expected that with careful screening, patients with established CAD can undergo ECT safely.     

The role of powered instrumentation in the surgical treatment of allergic fungal sinusitis

Allergic fungal sinusitis is a chronic disorder that is being more frequently recognized by otolaryngologists. It is a recurrent illness characterized by frequent exacerbations, and requires aggressive medical and surgical treatment. When surgical therapy is employed, it is necessary to ensure adequate debridement and removal of edematous tissue. We have been using powered dissection as our primary method in sinus surgery over the past three year. We have treated 11 patients with allergic fungal sinusitis, and find powered instrumentation to be very effective in removing the polypoid tissue from the nose and sinuses, and in providing a clear surgical field. The procedure can be performed safely with minimal trauma to normal tissue. We believe that the use of powered dissection greatly enhances the comprehensive treatment of allergic fungal sinusitis.     

On the use of the ratio or the odds ratio of cure rates in therapeutic equivalence clinical trials with binary endpoints

Acutely ill patients who are immunocompromised but not neutropenic most commonly are: (1) diabetic; (2) on chronic high-dose steroid therapy; (3) have lupus; or (4) have impaired or absent splenic function. These patients often present in the CCU because of the severity of their infection. Differential diagnosis may be approached by first considering the patient's underlying disease, i.e., SLE. The next step in the diagnostic process is to appreciate the immune defect associated with these disorders. The nature of the immune defect determines which clinical pathogens are related to the immune defect. Pathogens are associated with a sterotyped pattern of organ involvement. The object of the diagnostic analysis is to determine the most likely organism affecting a particular organ system, given the defect in host defenses associated with the patient's underlying illness. In this way, a useful clinical diagnosis can be made rapidly, and appropriate clinical specimens obtained for diagnostic testing. Often empiric therapy must be started pending the results of diagnostic testing. In such situations, empiric therapy ordinarily is directed against the bacterial pathogens most likely to cause disease relevant to the patient's impaired defenses. Specific therapy for unusual or exotic pathogens should not be empiric and should be based on demonstration of a pathogenic role by the microorganism. In the case of miliary tuberculosis or invasive fungal disease, a case may be made for early empiric therapy to cover these organisms if there is sufficient clinical suspicion based on the presenting signs and symptoms as well as the pattern of organ involvement. As with all infections, but particularly in immunocompromised patients, the early initiation of appropriate antimicrobial therapy is essential and often life-saving.     

Airway infection

Bronchitis in its acute and chronic forms with recurrent acute exacerbations is one of the most common reasons for physician visits, accounting for a significant cost to the health-care system, lost work days, and increased morbidity and mortality. Smoking and recurrent lower respiratory tract infections are major risk factors for chronic bronchitis. Therefore, smoking cessation and vaccination strategies are cornerstones of management in terms of halting disease progression and reducing the frequency of infectious exacerbations. Bacterial infection is the main culprit in acute flares of the disease. Routine antimicrobial therapy fails in a significant number of patients, and therapeutic failures lead to increased costs. Several stratification schemes have been proposed to improve initial antimicrobial selection. These schemes identify patient's age, severity of underlying pulmonary dysfunction, frequency of exacerbations, and the presence of comorbid illnesses as predictors for likely pathogens and to guide antimicrobial selection. This approach may reduce the risk for treatment failure, which would have significant medical and economic implications. Improved understanding of the roles of airway inflammation and infection in the pathogenesis of progressive airway disease, in addition to future studies examining the efficacy of newer classes of antimicrobials, should guide physicians to target early and effective treatment to high-risk patients.     

Therapy of sinuorbital aspergillosis with amphotericin B colloidal dispersion

Invasive aspergillosis is a feared complication in the management of patients with malignancies. We report a 13-year-old boy with acute myelogenous leukaemia and chronic sinusitis who developed a sinuorbital fungal infection during cytostatic and prolonged antibiotic treatment. The clinical findings, diagnostic measures and treatment and its adverse effects are described and discussed. Special emphasis is given to our experience of the use of colloidal dispersed amphotericin B (Amphocil).     

Removal of endotoxin and cytokines by plasma exchange in patients with acute hepatic failure

OBJECTIVES: To compare the circulating concentrations of endotoxin and cytokines in patients with fulminant hepatitis and patients with the severe form of acute hepatitis, and to assess the effects of plasma exchange on the circulating concentrations of these inflammatory mediators in patients with acute hepatic failure. DESIGN: Prospective, consecutive entry study of patients meeting fulminant hepatitis criteria and the severe form of acute hepatitis criteria. SETTING: University hospital, intensive care unit. PATIENTS: Five patients with fulminant hepatitis, eight patients with the severe form of acute hepatitis, two patients with acute-on-chronic hepatic failure, and one patient with postoperative hepatic failure. INTERVENTIONS: Plasma endotoxin, serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were determined on admission in five patients with fulminant hepatitis and eight patients with the severe form of acute hepatitis. Circulating concentrations of the inflammatory mediators were measured before and after a single course of plasma exchange in eight patients with acute liver failure, including five patients with fulminant hepatitis, two patients with acute-on-chronic hepatic failure, and one patient with postoperative hepatic failure. MEASUREMENTS AND MAIN RESULTS: TNF-alpha and IL-6 in patients with fulminant hepatitis were significantly higher than in patients with the severe form of acute hepatitis, whereas endotoxin concentrations did not differ between patients with fulminant hepatitis or the severe form of acute hepatitis. IL-1beta was not detectable in patients with either fulminant hepatitis or the severe form of acute hepatitis. Plasma endotoxin concentrations decreased immediately after plasma exchange. Serum concentrations of TNF-alpha and IL-6 were significantly lower after plasma exchange than before plasma exchange. CONCLUSION: TNF-alpha and IL-6 may be important in the pathogenesis of the clinical symptoms that differentiate fulminant hepatitis from the severe form of acute hepatitis, and plasma exchange removes these inflammatory mediators from the circulation of patients with severe liver disease.     

Paranasal sinus mycoses in north India

Recognizing the high incidence of paranasal sinus mycoses in north India, we analysed retrospectively the clinical, mycological and management aspects of 178 patients with proven disease attending our institute. On the basis of clinical, radiological, histopathological and mycological findings, the patients could be categorized into those with allergic (8), non-invasive (92) and invasive (78) disease types. Bony erosion without mucosal invasion by fungi was seen in 16 patients with non-invasive disease. Young men from rural areas were the most commonly affected. Rhinorrhoea with nasal polyposis (45.8%) and proptosis (46.4%) was the most common presentation. Concurrent involvement of the maxillary and ethmoid sinuses was common in these patients, whereas isolated sphenoid and frontal sinuses were involved in the invasive variety only. Orbital and intracranial extensions were detected in 100% and 13.2%, respectively, of patients with the invasive type of disease. Aspergillus flavus (79.7%) was the most common isolate. Surgical debridement and sinus ventilation were adequate for the effective management of the non-invasive disease. However, adjuvant medical therapy was included in treatment of the semi-invasive and invasive varieties of the disease. Itraconazole was found to be most useful in prevention of recurrence in the invasive type. Mortality was highest (33.3%) among patients with zygomycotic infection. Invasive fungal granuloma with orbital and intra-cranial invasion is a distinct entity in terms of its clinical course and treatment compared with non-invasive fungal sinusitis, and it needs to be treated aggressively with surgical excision and postoperative itraconazole.     

Genital infections and their care

The pathogenesis of hepatitis B can be subdivided into three sequentially correlated events: (a) loss of virus tolerance, (b) liver cell necrosis mediated by virus specific inflammatory response, (c) non-specific death of functionally compromised hepatocytes mediated by inflammatory cytochines released by virus specific inflammatory response. The severity of liver damage depends on the occurrence of these events as well as other factors. The HBeAg defective mutant appears to be involved in the loss of virus tolerance and therefore in the pathogenesis of acute hepatitis B. In addition it is positively selected by antiviral immunoreaction, behaves as an escape mutant, and it also contributes to the pathogenesis of chronic hepatitis B. The combination of these characteristics explains the relative prevalence of this mutant over wild-type HBV in patients with severe acute hepatitis B and in chronic HBsAg carriers during anti-HBe seroconversion and/or hepatitis B exacerbations. However, the absence of HBeAg defective mutants in some cases of severe and fulminant hepatitis B as well as its detection in asymptomatic carriers of HBsAg should not be surprising. The severity of hepatitis is influenced by many other factors: the number of virus infected cells, the competence and genetic heterogeneity of the immune system, the vigor and extent of non-specific inflammatory response and the killing of hepatocytes endangered by other diseases or infected with other hepatotropic viruses.     

Fatal invasive gastric mucormycosis occurring with emphysematous gastritis: case report and literature review

Emphysematous gastritis is an often lethal, rare clinical entity referring to air bubbles in the wall of the stomach produced by gas-forming bacteria. Invasive gastrointestinal mucormycosis is an unusual clinical presentation of this invasive fungal disease. We report the first case of invasive gastric mucormycosis occurring with emphysematous gastritis, and review the literature regarding both of these clinical entities.     

Effect of training on general practitioners'' use of a brief intervention for excessive drinkers

During recent years the outcome of acute hepatitis A in chronic liver disease has been discussed controversially. Data from large hepatitis A epidemics and surveillance data from the United States suggest a significantly higher risk of fatal outcome in patients with chronic hepatitis B. Patients with chronic active hepatitis or liver cirrhosis seem to be at highest risk, while HBsAg carriers may exhibit a benign course of the disease. Patients with chronic hepatitis C also seem to have a significantly higher risk of fulminant hepatic failure when superinfected with hepatitis A. The recently reported unsuspected coincidence of autoimmune markers with a fulminant course of hepatitis A in those patients needs to be confirmed. Vaccination against hepatitis A in patients with chronic liver disease has been shown to be safe and effective.     

An innovative method of reconstruction of large skeletal chest wall defects

A novel DNA virus, TT-virus (TTV), has been reported in patients with non-A-G posttransfusion hepatitis in Japan. We sought to determine whether TTV infection occurs in North American blood donors and to further determine the prevalence of TTV infection in several groups of patients with liver disease, including patients with cryptogenic cirrhosis and idiopathic fulminant hepatic failure. TTV infection was sought by detection of TTV DNA in serum by polymerase chain reaction (PCR) using primers generated from a conserved region of the TTV genome. Blood donors, patients with cryptogenic cirrhosis, idiopathic fulminant hepatic failure, and patients with other forms of advanced liver disease with and without a history of parenteral exposures were studied. TTV infection was present in 1% (1 of 100) of blood donors, 15% (5 of 33) of patients with cryptogenic cirrhosis, 27% (3 of 11) of patients with idiopathic fulminant hepatic failure, 18% (2 of 11) of patients with a history of exposure to blood products, and 4% (1 of 25) of patients without parenteral risk factors. For all patients tested, a history of prior exposure to blood products was associated with an increased risk of TTV infection (relative risk, 4.5; 90% confidence intervals, 0.6-43.9). We conclude that TTV infection is present among North American blood donors and is common in patients with liver disease, including cryptogenic cirrhosis and fulminant hepatic failure. Further studies are required to determine the role of TTV in the pathogenicity of acute and/or chronic liver disease.     

Production of fungal antigens from local strains for the immunodiagnosis of mycoses in Mexico

Allergic diseases caused by inhalant allergens are considered to be a major health problem. Allergic rhinitis, now affecting about 15% of the population, represents an inflammatory reaction, that may lead to asthma and chronic sinusitis as subsequent problems. Diagnosis should be based on a step-by-step concept, that also takes the clinical relevance of sensibilisations and other forms of nasal hyperreactivity into account. The aims of therapy are to limit the inflammatory reaction and to restore patient's quality of life. To achieve this goal, avoidance measures, immunotherapy and antiallergic drugs are currently used. The indication for and the performance of an immunotherapy demands special knowledge, and also the different drug activities and possible side effects should be thoroughly considered.