Value of determining carbohydrate-deficient transferrin isoforms in the diagnosis of alcoholic liver disease

OBJECTIVE: To determine whether isoform separation of carbohydrate-deficient transferrin (CDT) is of value in the diagnosis of alcoholic liver disease (ALD) and is specific to ALD when compared with other liver diseases. PATIENTS AND METHODS: During 1995 and 1996, 47 patients with ALD were evaluated with CDT at the Mayo Clinic in Rochester, Minn. The diagnosis of ALD was based on biochemical and histological analyses and on a history of drinking that exceeded 5 years with an average alcohol intake of more than 60 g/d. Disease controls included nonalcoholic steatohepatitis (NASH) (n = 26) and other liver disease (n = 22). Normal controls (n = 21) were healthy individuals without liver disease. Transferrin isoforms were quantified by densitometry of Coomassie-stained transferrins after affinity purification and isoelectric focusing. The pentasialo, tetrasialo, trisialo, disialo, monosialo, and asialo isoforms were quantified as percentages of total band densities. RESULTS: Receiver operating characteristic (ROC) curves were constructed for each isoform. The curves for total desialated isoforms (sum of disialo, monosialo, and asialo) displayed the best relationship between sensitivity and specificity with an ROC-area under the curve (AUC) of 0.922. The ROC-AUC values for individual transferrin isoforms in ALD vs NASH for pentasialo, tetrasialo, trisialo, disialo, monosialo, and asialo were 0.806, 0.917, 0.885, 0.933, 0.804, and 0.785, respectively. Only 58% of patients with ALD were detected at a specificity that excluded ALD in 84% of those who did not have it. CONCLUSION: Within alcohol ingestion times reported to us, no associations with recent drinking were observed. Alcohol as a cause of liver disease is not perfectly established by CDT analysis, although a high total CDT value favors ALD over NASH.     

Measurement of glycine in gray and white matter in the human brain in vivo by 1H MRS at 7.0 T

The concentration of glycine (Gly) was measured in gray matter (GM) and white matter (WM) in the human brain using single‐voxel localized ¹H MRS at 7 T. A point‐resolved spectroscopy sequence with echo time = 150 ms was used for measuring Gly levels in various regions of the frontal and occipital lobes in 11 healthy volunteers and one subject with a glioblastoma. The point‐resolved spectroscopy spectra were analyzed with LCModel using basis functions generated from density matrix simulations that included the effects of volume localized radio‐frequency and gradient pulses. The fraction of GM and white matter within the voxels was obtained from T₁‐weighted image segmentation. The metabolite concentrations within the voxels, estimated with respect to the GM + WM water concentrations, were fitted to a linear function of fractional GM content. The Gly concentrations in pure GM and white matter were estimated to be 1.1 and 0.1 mM, with 95% confidence intervals 1.0–1.2 and 0.0–0.2, respectively. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

Pathogens resistant to antibacterial agents

Resistance to antimicrobial drugs is increasing at an alarming rate among both gram-positive and gram-negative bacteria. Traditionally, bacteria resistant to multiple antimicrobial agents have been restricted to the nosocomial environment. A disturbing trend has been the recent emergence and spread of resistant pathogens in nursing homes, in the community, and in the hospital. This article reviews the epidemiology, molecular mechanisms of resistance, and treatment options for pathogens resistant to antimicrobial drugs.     

Chest radiograph vs. computed tomography scan in the evaluation for pneumonia

To determine, in an Emergency Department (ED) population, the incidence of pneumonia diagnosed on thoracic computed tomography (CT) in the setting of negative or non-diagnostic chest radiographs (CXR). This is a retrospective chart review of all ED visits of adult patients ultimately diagnosed with "pneumonia" in whom both CXR and CT were obtained. We note cases in which the CXR was either negative or non-diagnostic for pneumonia and the CT noted a definitive infiltrate consistent with pneumonia. Of the 1,057 patients diagnosed with pneumonia, both CXR and CT were performed in 97 cases. Of this group, there were 26 patients (27%), in whom the CXR was either negative or non-diagnostic, but the CT noted an infiltrate/consolidation consistent with pneumonia. In our retrospective review of ED patients, we find that in 27% of cases in which both a CXR and a CT scan were performed in the work-up of varied chief complaints, pneumonia was demonstrated on CT in the face of a negative or non-diagnostic CXR. This analysis demonstrates the need for further studies regarding the appropriate radiographic evaluation of pneumonia, particularly in high-risk patients.     

Staggered transition to epoprostenol from treprostinil in pulmonary arterial hypertension

OBJECTIVE: To describe a successful transition process from subcutaneous treprostinil to intravenous epoprostenol after the failure of treprostinil in a patient with idiopathic pulmonary arterial hypertension and present an algorithm to achieve the conversion without significant adverse reactions. CASE SUMMARY: A 25-year-old white female receiving subcutaneous treprostinil 97 ng/kg/min was admitted to the intensive care unit for transition from subcutaneous treprostinil to a target intravenous epoprostenol dose of 72 ng/kg/min via a staggered interval dose adjustment approach. The patient experienced facial flushing, hot flashes, and headache when dose adjustments of the drugs were made simultaneously; however, when dose adjustments were staggered, the adverse reactions did not occur and larger adjustments could be achieved. DISCUSSION: This case demonstrates a suboptimal therapeutic response to treprostinil for the treatment of idiopathic pulmonary arterial hypertension. The transition of treprostinil to epoprostenol is rare; however, in the event therapy change is needed, dosing information is minimal. A staggered transition dosing regimen that accounts for the pharmacokinetic differences between epoprostenol and treprostinil was successfully used in this case. CONCLUSIONS: The approach in this case demonstrates the success of staggered-interval dose adjustments to minimize supratherapeutic symptoms and coincides with the pharmacokinetic profile of the 2 medications.     

Australian Implementation and Evaluation of Active Support

Background The implementation and evaluation of Active Support in Australia is reported, the first such formal evaluation outside the UK. Method Residents and staff of five group homes participated. Active Support was introduced by training staff in one home at a time. Effectiveness was assessed using direct observation of resident engagement in activity and of staff help, as well as written assessments of resident outcomes. Results Staff help and resident engagement increased in four of five group homes. There was significantly greater participation in a wider variety of domestic activities, as well as more frequent and varied community participation. Change in resident engagement was positively related to change in staff help, but not related to residents’ level of adaptive behaviour. Conclusions Most of our findings were consistent with earlier UK studies. There was evidence of the successful transfer of Active Support training skills to an Australian training team. Nonsignificant trends towards reduced depression and increased adaptive behaviour warrant further investigation.     

Leisure Time Physical Activity in a Population-Based Sample of People With Spinal Cord Injury Part I: Demographic and Injury-Related Correlates

Martin Ginis KA, Latimer AE, Arbour-Nicitopoulos KP, Buchholz AC, Bray SR, Craven BC, Hayes KC, Hicks AL, McColl M, Potter PJ, Smith K, Wolfe DL. Leisure time physical activity in a population-based sample of people with spinal cord injury part I: demographic and injury-related correlates.

Objectives

To estimate the number of minutes a day of leisure time physical activity (LTPA) performed by people with chronic spinal cord injury (SCI) and to identify the demographic and injury-related characteristics associated with LTPA in a population-based sample of people with chronic SCI.

Design

Cross-sectional telephone survey.

Setting

General community.

Participants

Men and women with SCI (N=695).

Interventions

Not applicable.

Main Outcome Measures

The number of minutes/day of LTPA performed at a mild intensity or greater.

Results

Respondents reported mean minutes ± SD of 27.14±49.36 of LTPA/d; however, 50% reported no LTPA whatsoever. In a multiple regression analysis, sex, age, years postinjury, injury severity, and primary mode of mobility each emerged as a unique predictor of LTPA. Multiple correspondence analysis indicated that being a man over the age of 34 years and greater than 11 years postinjury was associated with inactivity, while being a manual wheelchair user and having motor complete paraplegia were associated with the highest level of daily LTPA.

Conclusions

Daily LTPA levels are generally low in people with SCI. Women, older adults, people with less recent injuries, people with more severe injuries, and users of power wheelchairs and gait aids are general subgroups that may require special attention and resources to overcome unique barriers to LTPA. Specific subgroups may also require targeted interventions.     

Discovery and characterization of QPT-1, the progenitor of a new class of bacterial topoisomerase inhibitors

QPT-1 was discovered in a compound library by high-throughput screening and triage for substances with whole-cell antibacterial activity. This totally synthetic compound is an unusual barbituric acid derivative whose activity resides in the (-)-enantiomer. QPT-1 had activity against a broad spectrum of pathogenic, antibiotic-resistant bacteria, was nontoxic to eukaryotic cells, and showed oral efficacy in a murine infection model, all before any medicinal chemistry optimization. Biochemical and genetic characterization showed that the QPT-1 targets the beta subunit of bacterial type II topoisomerases via a mechanism of inhibition distinct from the mechanisms of fluoroquinolones and novobiocin. Given these attributes, this compound represents a promising new class of antibacterial agents. The success of this reverse genomics effort demonstrates the utility of exploring strategies that are alternatives to target-based screens in antibacterial drug discovery.