Citations

Drugs that target novel surfaces on the androgen receptor (AR) and/or novel AR regulatory mechanisms are promising alternatives for the treatment of castrate-resistant prostate cancer. The 52 kDa FK506 binding protein (FKBP52) is an important positive regulator of AR in cellular and whole animal models and represents an attractive target for the treatment of prostate cancer. We used a modified receptor-mediated reporter assay in yeast to screen a diversified natural compound library for inhibitors of FKBP52-enhanced AR function. The lead compound, termed MJC13, inhibits AR function by preventing hormone-dependent dissociation of the Hsp90-FKBP52-AR complex, which results in less hormone-bound receptor in the nucleus. Assays in early and late stage human prostate cancer cells demonstrated that MJC13 inhibits AR-dependent gene expression and androgen-stimulated prostate cancer cell proliferation.

BACKGROUND: Many patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) have had recent healthcare interventions prior to developing ALI/ARDS. OBJECTIVE: To determine the timing of ALI/ARDS onset in relation to hospital admission and other healthcare interventions. METHODS: We conducted a population-based observational cohort study with a validated electronic surveillance tool, and identified patients with possible ALI/ARDS among critically ill adults at Mayo Clinic hospitals that provide critical care services for Olmsted County, Minnesota, in 2006. Trained investigators independently reviewed electronic medical records and confirmed the presence and timing of ALI/ARDS based on the American-European consensus definition. RESULTS: Of 124 episodes of ALI in 118 patients, only 5 did not fulfill the ARDS criteria. The syndrome developed a median 30 hours (IQR 10–82 h) after hospital admission in 79 patients (67%). ARDS was present on admission in 39 patients (33%), of whom 14 had recent hospitalization, 6 were transferred from nursing homes, and 3 had recent out-patient contact (1 antibiotic prescription, 1 surgical intervention, and 1 chemotherapy). Only 16 ARDS patients (14%) did not have known recent contact with a healthcare system. Compared to ARDS on admission, hospital-acquired ARDS was more likely to occur in surgery patients (54% vs 15%, P < .001), and had longer adjusted hospital stay (mean difference 8.9 d, 95% CI 0.3–17.4, P = .04). CONCLUSIONS: ARDS in the community most often develops either during hospitalization or in patients who recently had contact with a healthcare system. These findings have important implications for potential preventive strategies.

Introduction: Nummular headache is a rare primary headache disorder described by a focal circumscribed area of pain (2–6 cm in diameter). Literature on this disorder is sparse. Patients and methods: Here, we describe a case series of 16 patients (6 men, 10 women) seen at the Mayo Clinic. Results: Mean age of onset was 50 years (range, 19–79 years) and mean duration of headache was 7.9 years (range, 0.33–40 years). Location of headache varied and was found to be an average of 3.9 cm in diameter (range, 2–10 cm). Headache was episodic (<15 days/month) in four patients and chronic (>15 days/month) in 12 patients. Attention was paid to therapeutic interventions. Resolution was seen in 38% of patients. Migraine was present in the history of 56% of patients and medication overuse headache was found in 25%. Conclusions: Our series results support previous findings. In our population, no specific therapy was identified to be effective in more than one patient.

The trigeminal trophic syndrome is an unusual consequence of trigeminal nerve injury that results in facial anaesthesia, dysaesthesia and skin ulceration. Limited knowledge is available. The aim of this study was to increase the knowledge of this syndrome by performing a retrospective medical record review and case series report. Fourteen cases were identified. The female : male ratio was 6:1. Mean age of onset was 45 years (range 6-82). The cause was iatrogenic in most. Latent period to onset ranged from days to almost one decade. The majority ( n = 12) had bothersome dysaesthesias. Most ( n = 9) self-manipulated the face; a third ( n = 5) did not. Most ulcers affected the second trigeminal division, mainly in the infraorbital nerve distribution. Neuropathic and/or neuralgic facial pain occurred in 50% ( n = 7). Pain intensity was severe in most (n = 6). Gabapentin gave relief in two. To conclude, trigeminal trophic syndrome follows injury to the trigeminal nerve or its nuclei. For unclear reasons, most ulcerations follow infraorbital nerve distribution. Self-manipulation may contribute to ulcer development rather than being required. Gabapentin may help pain.