All in the family: atypical Hsp70 chaperones are conserved modulators of Hsp70 activity.

Divergent relatives of the Hsp70 protein chaperone such as the Hsp110 and Grp170 families have been recognized for some time, yet their biochemical roles remained elusive. Recent work has revealed that these "atypical" Hsp70s exist in stable complexes with classic Hsp70s where they exert a powerful nucleotide-exchange activity that synergizes with Hsp40/DnaJ-type cochaperones to dramatically accelerate Hsp70 nucleotide cycling. This represents a novel evolutionary transition from an independent protein-folding chaperone to what appears to be a dedicated cochaperone. Contributions of the atypical Hsp70s to established cellular roles for Hsp70 now must be deciphered.

Non-staphylococcal infections of cardiac implantable electronic devices

Background. The number of infections of cardiac implantable electronic devices (CIED) continues to escalate out of proportion to the increase rate of device implantation. Staphylococcal organisms account for 70% to 90% of all CIED infections. However, little is known about non-staphylococcal infections, which have been described only in case reports, small case series or combined in larger studies with staphylococcal CIED infections, thereby diluting their individual impact. ^ Methods. A retrospective review of hospital records of patients admitted with a CIED-related infections were identified within four academic hospitals in Houston, Texas between 2002 and 2009. ^ Results. Of the 504 identified patients with CIED-related infection, 80 (16%) had a non-staphylococcal infection and were the focus of this study. Although the demographics and comorbities of subjects were comparable to other reports, our study illustrates many key points: (a) the microbiologic diversity of non-staphylococcal infections was rather extensive, as it included other Gram-positive bacteria like streptococci and enterococci, a variety of Gram-negative bacteria, atypical bacteria including Nocardia and Mycobacteria, and fungi like Candida and Aspergillus; (b) the duration of CIED insertion prior to non-staphylococcal infection was relatively prolong (mean, 109 ± 27 weeks), of these 44% had their device previously manipulated within a mean of 29.5 ± 6 weeks; (c) non-staphylococcal organisms appear to be less virulent, cause prolonged clinical symptoms prior to admission (mean, 48 ± 12.8 days), and are associated with a lower mortality (4%) than staphylococcal organisms; (d) thirteen patients (16%) presented with CIED-related endocarditis; (e) although not described in prior reports, we identified 3 definite and 2 suspected cases of secondary Gram-negative bacteremia seeding of the CIED; and (f) inappropriate antimicrobial coverage was provided in approximately 50% of patients with non-staphylococcal infections for a mean period of 2.1 days. ^ Conclusions. Non-staphylococcal CIED-related infections are prevalent and diverse with a relatively low virulence and mortality rate. Since non-staphylococcal organisms are capable of secondarily seeding the CIED, a high suspicion for CIED-related infection is warranted in patients with bloodstream infection. Additionally, in patients with suspected CIED infection, adequate Gram positive and -negative antibacterial coverage should be administered until microbiologic data become available.^

EPIDEMIOLOGIC TRENDS OF LUNG DISEASE DUE TO MYCOBACTERIA KANSASII AND AVIUM-INTRACELLULARE IN TEXAS, 1977-1983

This study compared the reported isolations of Mycobacterium kansasii (MK) and Myobacterium avium-intracellulare (MAI) with Mycobacterium tuberculosis (MTB) between 1977-1983 in Texas. A total of 15,395 mycobacterial cases were identified of which 1,352 (8.8%) were MK or MAI. The incidence of MK was higher in urban areas than nonurban areas (p < .005). The incidence of MAI has increased in the Dallas metroplex from 34 cases to 251 for the same time period. Although the number of MK cases previously reported has always exceeded those of MAI, the numbers were equal in the last year (1983) of the study.^ More than 75% of patients with MK or MAI were Caucasians compared to only 18% of patients with MTB. Male to female ratios for MK and MAI are 3:1 and 3:2, respectively. The age distribution of MK patients were an average of 5 years younger than patients with MAI, a finding which concurs with previous studies. MK and MAI pulmonary infections continue to be absent among children and relatively absent among Hispanics.^ MK appears to be associated with occupations in construction, whereas MAI is more often associated with farm work. ^

Retrospective assesment of the levonorgestrel intrauterine device to treat complex atypical hyperplasia and early endometrioid endometrial cancer

Objective: The primary objective of this project was to describe the efficacy of the Levonorgestrel Intrauterine Device (LIUD) for treatment of Complex Endometrial Cancer (CAH) and Grade 1 Endometrial Cancer (G1EEC) in terms of rate of Complete Response (CR) and Partial Response (PR) after 6 months of therapy. Finally, we assessed if any clinical or pathologic features were associated with response to the LIUD. ^ Methods: This study was a retrospective case series designed to report the response rate of patients with CAH or G1EEC treated with LIUD therapy. In addition, this study has a laboratory component to assess molecular predictors of response to LIUD therapy. Retrospective data already collected from patients diagnosed with CAH or EEC grade 1 and treated with LIUD therapy at MD Anderson Cancer Center (MDACC) were used for this study. Patients from all ethnic and race groups were included. A Complete Response (CR) was defined in patients diagnosed with CAH if pathologic report at 6 months demonstrated either no evidence of hyperplasia or no atypia in the setting of simple or complex hyperplasia. Partial Response (PR) was recorded if disease downgraded to only CAH from G1EEC. No Response (NR) was recorded if pathologic report demonstrates no change (Stable Disease, SD) or progression to cancer (Progressive Disease, PD). We calculated the proportion of patients with complete response to LIUD therapy with 95% confidence interval. We compared the response rates (CR/PR vs NR) by obesity status (Obese if BMI > 40 kg/m2 vs non-obese if BMI <= 40 kg/m2) as well as other clinical and pathologic factors, such as age, uterine size (median size), and presence of exogenous progesterone effect. ^ Results: There were 39 patients diagnosed with either CAH or G1EEC treated with the LIUD. Of 39 patients, 12 did not have pathological results of biopsy at 6months time period. Of 27 evaluable patients, 17 were diagnosed with CAH and 10 with G1EEC. Overall response rate (RR) was 78% (95% CI = 62-94%) at 6 months, 18 patients had CR (4 in G1EEC; 14 in CAH), 3 patients had PR (3 in G1EEC), 3 had SD (1 in CAH; 2 in G1EEC), 3 had PD (2 in CAH; 1 in G1EEC). After histology stratification, RR at 6 months was 82.35% (14/17; 95%CI = 67.4-97.3%) in CAH and 70% (7/10; 95% CI = 41-98.4%) in G1EEC. ^ There was no difference in response (R) and no response (NR) based on BMI (p=0.56). He observed a trend showing association between age with response (p=0.1). There was no association between uterine size and response to therapy (p=0.17). We recorded strong association between exogenous progesterone effect and response. ^ Conclusion: LIUD therapy for the treatment of CAH and G1EEC may be effective and safe. Presence of exogenous progesterone effect may predict the response to LIUD therapy at earlier time points. There is need of further studies with larger sample size to explore the relationship of response with other clinical and pathologic factors^