Immunomodulation of invasive fungal infections

Genetic and acquired (disease- or therapy- related) host immune factors increase the risk for IFIs. In addition to antifungal drug therapy, modulation of host defenses by the use of HGFs and IFN-gamma has been supported by extensive in vitro and in vivo preclinical data. Clinical studies on the prevention or the adjunctive therapy of IFIs in combination with antifungal agents are limited, however, and do not allow specific recommendations for their cost-effective use in most of the immunodeficient settings. There is an urgent need to push forward with well-structured, randomized clinical trials to determine optimal dose, duration, and timing for different combinations of immunotherapy and antifungal agents in high-risk patients.     

Trichosporon asahii: an unusual cause of invasive infection in neonates

Trichosporon asahii causes white piedra, an infection of hair shafts and onychomycosis in immunocompetent patients, as well as various localized or disseminated invasive infections in immunodeficient hosts. We describe a 26-week gestation 890-g vaginally delivered female neonate who had severe respiratory distress syndrome and on the sixth day of life developed Klebsiella pneumoniae sepsis. At the same time two blood cultures were positive for T. asahii. The neonate was also colonized with T. asahii in the pharynx and perineum. The infant was successfully treated with conventional amphotericin B.     

Recurrence of sciatica following hemilaminectomy for disc herniation

This retrospective study investigated the causes of ipsilateral sciatica following formal hemilaminectomy and discectomy for disc herniation and analyzed the factors that influence the outcome of revision surgery for recurrence. From a series of 1,016 patients who were operated upon for primary lumbar disc herniation, 64 patients were revised because of persistent or recurrent sciatica and back pain. Successful outcome was achieved in 81% of the patients with pain recurrence within 6 months following unilateral disc herniation at another level, residual disc herniation, recurrence of disc herniation, pseudomeningocele, and epidural hematoma. In contrast, not successful results were noted in the other 19% of reoperated patients later than 6 moths following primary operation for epidural fibrosis, lateral spinal stenosis, or combined. In this series, the outcome following revision surgery was not related to any specific clinical symptoms and physical examination findings, but mainly to the operative findings during revision surgery and the time lapsed between primary and revision surgery. Computed tomography (CT) was less reliable than magnetic resonance imaging (MRI) in detecting pathology prior to revision surgery, particularly in distinguishing between disc prolapse and fibrosis. Operative findings and pain-free interval between primary discectomy and revision surgery determined the outcome of revision surgery for recurrent ipsilateral sciatica, while MRI seems to be the imaging method of choice. Revision surgery for ipsilateral radicular pain following discectomy in this series showed satisfactory results that were comparable with those of primary discectomy.     

Application of denaturing gradient gel electrophoresis (DGGE) to screen for mutations of the human glucocorticoid receptor alpha gene (hGRalpha)

OBJECTIVES: In a previous publication, we had presented a sensitive method to detect mutations of the segment of the human glucocorticoid receptor alpha (hGRalpha) gene encoding the ligand binding domain (LBD) and part of the DNA binding domain (DBD) of hGRalpha, as several types of glucocorticoid resistance syndromes have been correlated with mutations in the respective nucleotide sequences. However, mutations affecting various regions covering the whole length of hGRalpha are increasingly reported in a variety of disease states. We now present an expanded screening methodology to detect mutations covering the whole length of hGRalpha. DESIGN AND METHODS: We developed a sensitive, simple screening PCR-DGGE method to detect mutations in the aminoterminal domain and DNA-binding domain of the hGRalpha. Wild type hGRalpha cDNA and mutant samples were included in the analysis to ensure the accuracy and sensitivity of the method. RESULTS: The PCR-DGGE method identified the mutant samples and discriminated them from wild type hGRalpha. CONCLUSIONS: The method described is accurate, sensitive, simple, cheap and fulfills the critera for a screening method which will be useful in delineating possible involvement of hGRalpha mutations in the aetiopathology of diseases correlated to derangements of glucocorticoid action.     

Esthesioneuroblastoma: the Northwestern University experience

OBJECTIVE: To review our experience with esthesioneuroblastoma, a rare malignancy of the head and neck. STUDY DESIGN: Retrospective review of Tumor Registry data. METHODS: We performed a computerized search of the Northwestern Memorial Hospital Tumor Registry database from 1981 to 2000. RESULTS: Sixteen patients with esthesioneuroblastoma were identified and analyzed. Their mean age was 42 years. Eleven of 16 patients (69%) had Kadish stage C; 8 patients (50%) had brain involvement at presentation. Craniofacial resection was performed in 13 patients (81%). Fourteen patients received either preoperative or postoperative therapy; radiation therapy was employed in 11 cases and chemotherapy in 4. The actuarial 5-year survival was 60%, and the actuarial 5-year disease-free survival was 33%, with a median follow-up of 4.3 years. Recurrences occurred at a median time of 11 months after diagnosis (2.5 mo-18 y). The first site of failure was locoregional alone in 10 of 12 patients who progressed, and in 6 patients involved the brain or the meninges. Two patients were successfully salvaged. Patients with high-grade tumors had a trend toward work survival. CONCLUSIONS: Esthesioneuroblastoma is a rare tumor that is potentially curable by surgical resection and radiation therapy. However, the rate of local failure is high, and late recurrences are not uncommon. The role of chemotherapy warrants further investigation.     

Arsonoliposomes for the Potential Treatment of Medulloblastoma

Purpose  

To investigate the arsonoliposome effect on medulloblastoma cells (VC312Rs) related to uptake, endocytotic mechanism and cell viability.     

Adrenal function in non-septic long-stay critically ill patients: evaluation with the low-dose (1 micro g) corticotropin stimulation test

OBJECTIVE: To investigate the adrenal function in non-septic, long-stay critically ill patients. DESIGN: Prospective, consecutive study. SETTING: General intensive care unit in a university hospital. PATIENTS: Forty-three non-septic patients with protracted critical illness. INTERVENTIONS: A morning blood sample was first obtained to measure baseline plasma cortisol. Subsequently, 1 micro g of corticotropin (ACTH, Synacthene) was injected intravenously and 30 min later a second blood sample was drawn to determine stimulated plasma cortisol. Patients having a stimulated cortisol level of at least 18 micro g/dl were defined as responders. In 36 patients, morning interleukin-6 (IL-6) was also measured. MEASUREMENTS AND RESULTS: Baseline and stimulated plasma cortisol were 16.8+/-4.1 micro g/dl and 21.2+/-5.1 micro g/dl, respectively. Interleukin-6 was high (median 39.3 pg/ml, interquartile range 24.9-86.6 pg/ml) and correlated negatively with stimulated plasma cortisol (r=-0.40, p<0.05). Of the 43 patients studied, 31 patients (72%) were responders and 12 patients (28%) were non-responders to the ACTH stimulation test. Overall, 18 patients died and 25 patients survived to hospital discharge. Non-responders had significantly higher IL-6 levels compared to responders (106+/-73 versus 48+/-42 pg/ml, p<0.05), whereas mortality rate was comparable in the two groups (50% versus 38%, p=0.74). CONCLUSIONS: Circulating plasma IL-6 levels are high during protracted critical illness, and are partially responsible for the relative adrenal insufficiency found in a subset of severely ill patients.     

“I’m Coming Home,Tell the World I’m Coming Home”. The Long Homecoming and Mental Health Treatment of Iraq and Afghanistan War Veterans

This study explored the journey of American armed forces personnel from their decision to join the service, through their service in an active military conflict and how these factors may be associated with potential resistance for mental healthcare. The data came from qualitative interviews with 46 OIF/OEF/OND active-duty military, reservists, and discharged veterans of the average age of 25 years, who presented for a new episode of mental health treatment to a large Veterans Affairs Hospital (VAH) in Northeastern United States in 2011–2012. Qualitative analysis of veterans’ perceptions revealed several major themes describing how a mental health diagnosis would negatively impact both their sense of identity and pragmatic career-building goals: enlisting as a career-building avenue, ‘noble superhero’ identity, escaping from hardship, and mental illness as a career-killer. Findings suggest that factors making young veterans resist mental healthcare may be reduced by partnering VAH psychiatrists with career counselors, and by enhancing military leadership’s awareness and understanding about how to support soldiers with emotional and mental health needs, with a goal to eliminating stigma.