Expression of alpha-defensin-1 in chronic hyperplastic candidosis

BACKGROUND: Chronic hyperplastic candidosis (CHC) represents a chronic opportunistic candida infection. We clarified the presence, localization and participation of alpha-defensin-1 in host response against chronic candidal stimulus. METHODS: Immunohistochemically stained CHC biopsies (n = 10) were compared to candida negative idiopathic leukoplakia (n = 10). RESULTS: In CHC alpha-defensin-1 was detected in neutrophils intravascularly, in lamina propria and in the epithelium, in part in intraepithelial microabscesses. Staining intensity of individual neutrophils varied and was associated with peri- and extracellular staining, in particular in the superficial epithelial cell layers. In controls only very few homogeneously staining neutrophils were detected intravascularly without any extracellular alpha-defensin-1 deposition. CONCLUSIONS: Neutrophils form microabscesses and respond to Candida by activation and release of alpha-defensin-1 to peri- and extracellular matrix. This together with the epithelial cell migration from the basal layer to epithelial surface leads to alpha-defensin-1 rich protective shield in the most superficial epithelial cell layers.     

Mutant ryanodine receptors in catecholaminergic polymorphic ventricular tachycardia generate delayed afterdepolarizations due to increased propensity to Ca2+ waves.

AIMS: Mutations in cardiac ryanodine receptors (RyR2s) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), characterized by risk of polymorphic ventricular tachyarrhythmias and sudden death during exercise. Arrhythmias are caused by gain-of-function defects in RyR2, but cellular arrhythmogenesis remains elusive. METHODS AND RESULTS: We recorded endocardial monophasic action potentials (MAPs) at right ventricular septum in 15 CPVT patients with a RyR2 mutation (P2,328S, Q4,201R, and V4,653F) and in 12 control subjects both at baseline and during epinephrine infusion (0.05 microg/kg/min). At baseline 3 and during epinephrine infusion, four CPVT patients, but none of the control subjects, showed delayed afterdepolarizations (DADs) occasionally coinciding with ventricular premature complexes. In order to study the underlying mechanisms, we expressed two types of mutant RyR2 (P2,328S and V4,653F) causing CPVT as well as wild-type RyR2 in HEK 293 cells. Confocal microscopy of Fluo-3 loaded cells transfected with any of the three RyR2s showed no spontaneous subcellular Ca(2+) release events at baseline. Membrane permeable cAMP analogue (Dioctanoyl-cAMP) triggered subcellular Ca(2+) release events as Ca(2+) sparks and waves. Cells expressing mutant RyR2s showed spontaneous Ca(2+) release events at lower concentrations of cAMP than cells transfected with wild-type RyR2. CONCLUSION: CPVT patients show DADs coinciding with premature action potentials in MAP recordings. Expression studies suggest that DADs are caused by increased propensity of abnormal RyR2s to generate spontaneous Ca(2+) waves in response to cAMP stimulation. Increased sensitivity of mutant RyR2s to cAMP may explain the occurrence of arrhythmias during exercise or emotional stress in CPVT.     

The ostiomeatal unit and endoscopic surgery: anatomy, variations, and imaging findings in inflammatory diseases.

Recent and ongoing advances made in endoscopic surgical techniques require the radiologist to understand the anatomy and pathophysiology of the paranasal sinuses and nasal passage. Endoscopy and CT are complementary procedures, and, as such, the normal anatomic relationships and their CT appearances need to be well understood in order for radiologists to offer continued support as consultants to their clinical colleagues. In this article, we review the pertinent anatomy of the lateral nasal wall and paranasal sinuses, discuss the most frequently encountered normal variations that may predispose a patient to inflammatory sinus disease, outline imaging protocols for evaluation of this region, and introduce the reader to current endoscopic surgical techniques. Last, the imaging findings in various inflammatory processes involving the sinuses, as well as the local and regional complications associated with paranasal sinus inflammatory diseases, are presented.     

Glove perforations in open and laparoscopic abdominal surgery: the feasibility of double gloving.

BACKGROUND AND AIMS: According to the traditional view, the glove protects the patient from the bacterial growth of the surgeons' hands and doing so prevents infections. Today, with growing incidences of HIV and Hepatitis B and C, surgical gloves are also important as protection for the surgeon. We compared the safety of double indicator gloves to standard single surgical gloves by investigating how often surgical gloves are punctured in laparoscopic and open gastrointestinal surgery. STUDY: As study material we gathered all gloves that had been used in gastrointestinal surgery in Satakunta Central Hospital during two months. 814 gloves from 274 operations were tested by using standardized water filling test method. RESULTS: In open surgery 67 gloves out of 694 had been punctured (9.6 percent). Puncture occurred in 22.5 percent of operations (53 out of 236). During open surgery 24 holes out of 35 were undetected with single gloves (69 percent). With double indicator gloves, only 3 out of 31 holes were unnoticed (10 percent). Long duration of operation increased the risk of puncture. In laparoscopic operations 4 gloves out of 120 had been perforated (3.3 percent). CONCLUSION: Double surgical gloves give markedly better protection in surgery. This is important especially in high risk operations.     

Fluconazole compared with ketoconazole for the treatment of Candida esophagitis in AIDS. A randomized trial.

OBJECTIVE: To determine the clinical and endoscopic response of candida esophagitis to antifungal therapy and to compare the two oral antifungal agents, fluconazole and ketoconazole. DESIGN: Multicenter, randomized, double-blind trial. SETTING: Fifteen U.S. centers including university, private practice, and county hospital settings. PATIENTS: A total of 169 patients with the acquired immunodeficiency syndrome (AIDS); odynophagia, dysphagia, or retrosternal pain; white esophageal plaques at endoscopy; and pseudohyphae on esophageal brushings or biopsies. INTERVENTION: Patients were randomly assigned to fluconazole (100 mg/d) or ketoconazole (200 mg/d). Doses were doubled at week 1 or 2 if no symptomatic improvement had occurred during the preceding week. Therapy was continued for 2 weeks after resolution of symptoms or for a maximum of 8 weeks. MEASUREMENTS: Patients were clinically evaluated weekly, and laboratory tests were done every 2 weeks. Endoscopy was repeated within 5 days after the end of therapy. RESULTS: A total of 143 patients were clinically evaluable (assessed within 7 days after therapy), and 129 patients were endoscopically evaluable (endoscopy repeated after therapy). Endoscopic cure occurred in 91% of patients treated with fluconazole and in 52% of those given ketoconazole for a difference of 39% (95% Cl, 24% to 52%; P less than 0.001). Esophageal symptoms resolved in 85% of fluconazole-treated patients and in 65% of ketoconazole-treated patients for a difference of 20% (Cl, 6% to 34%; P = 0.006). Intention-to-treat analyses also yielded statistically significant differences for the comparisons listed above. Side effects were minimal and comparable in the two groups; only one patient in each group had therapy discontinued for adverse effects that were possibly related to the study medications. CONCLUSIONS: Fluconazole is associated with significantly greater rates of endoscopic and clinical cure than ketoconazole in patients with AIDS and candida esophagitis. Both drugs appear to be safe and well tolerated.     

Uncomplicated amebic liver abscess: prospective evaluation of percutaneous therapeutic aspiration.

The performance of therapeutic aspiration in the treatment of amebic liver abscess, advocated and practiced in many centers, is controversial. Previously, this practice has been evaluated in retrospective analyses. To test the potential benefit of therapeutic aspiration, the authors undertook a prospective randomized trial in 57 patients admitted for suspected amebic liver abscess during a 15-month period. Sixteen patients were excluded from the trial. The remaining 41 patients were randomly included in one of two study groups to receive amebicidal therapy alone or amebicidal therapy coupled with image-guided percutaneous therapeutic aspiration. All patients in the trial recovered. No statistically significant benefit was demonstrated in the aspiration group for the two objective parameters evaluated: length of hospitalization and duration of time to becoming afebrile. Subjective improvement in symptoms after aspiration was greater in the aspiration group at a marginally statistically significant level. These data do not support the adjunctive performance of percutaneous therapeutic aspiration in the treatment of uncomplicated amebic liver abscess. Amebicidals alone were equally efficacious in treating the group studied.