Hepatocellular carcinoma: assessment of resectability by computed tomography and ultrasound

A retrospective review of the CT and ultrasound scans from examinations of 30 patients who had hepatocellular carcinoma (hepatoma) was undertaken with special emphasis placed on evaluation of hepatic distribution of tumor, vascular invasion, and extrahepatic spread. Although both CT and ultrasound detected hepatoma in 29 of 30 patients (96%), CT showed more extensive hepatic parenchymal involvement in eight of the patients. Vascular invasion was seen more frequently with ultrasound than with CT. Invasion into the main portal vein was seen by ultrasound in 11 of 30 patients (37%). Extrahepatic spread of tumor was much more frequently detected by CT and was present in 21 of 30 patients (70%). A reasoned approach to the diagnostic workup of hepatomas that will minimize invasive procedures and unnecessary surgery is presented.     

Self-limiting extravasation in the unused urinary bladder

Patients being evaluated as potential renal transplant recipients routinely undergo voiding cystourethrography. Eight patients were encountered in whom extraperitoneal extravasation was noted from the region of the ureterovesical junction during voiding (seven patients) or during filling (one patient). Extravasation was bilateral in six patients and unilateral in two. The patients neither experienced symptoms related to the extravasation, required treatment, nor had sequelae. Five of the eight patients have subsequently received renal transplants and their bladders were observed to be normal at surgery. Cystoscopy was also performed in two of these five patients and was unremarkable. After transplantation, these patients' bladders functioned normally and gave rise to no symptoms.     

Epidemiologic background and long-term course of disease in human immunodeficiency virus type 1-infected blood donors identified before routine laboratory screening. Transfusion Safety Study Group

BACKGROUND: The long-term course of human immunodeficiency virus type 1 (HIV-1)-related disease among seropositive blood donors has not been described. The enrollment and epidemiologic background of HIV-1- infected donors in the Transfusion Safety Study and their immunologic and clinical progression are described. STUDY DESIGN AND METHODS: Through the testing of approximately 200,000 sera from donations made in late 1984 and early 1985, 146 anti-HIV-1-positive donors and 151 uninfected matched donors were enrolled. These two cohorts were followed with 6-month interval histories and laboratory testing. RESULTS: Seropositive donors detected before the institution of routine anti-HIV-1 screening disproportionately were first-time donors and men with exclusively male sexual contacts. The actuarial probability of a person's developing AIDS within 7 years after donation was 40 percent; the probability of a person's dying of AIDS was 28 percent. AIDS developed more often when the donor was p24 antigen-positive at donation. Over a 3-year period, significant decreases occurred in CD4+, CD2+CD26+, CD4+CD29+, and CD20+CD21+ counts, but not in CD8+ subsets, CD20+, or CD14+. CONCLUSION: The high proportions of first-time donations and exclusively homosexual men among seropositive donors suggest that test-seeking may have contributed to the high HIV-1 prevalence in the repository. Implementation of alternative test sites when routine donor screening began in 1985 may have averted many high- risk donations. The disease course in HIV-1-infected donors had the same wide spectrum of immunologic and clinical manifestations as were reported for other cohorts.     

What do we know about how to do audit and feedback? Pitfalls in applying evidence from a systematic review

Background  

Improving the quality of health care requires a range of evidence-based activities. Audit and feedback is commonly used as a quality improvement tool in the UK National Health Service [NHS]. We set out to assess whether current guidance and systematic review evidence can sufficiently inform practical decisions about how to use audit and feedback to improve quality of care.     

The effects of whole‐body vibration training and vitamin D supplementation on muscle strength,muscle mass,and bone density in institutionalized elderly women: A 6‐month randomized,controlled trial

Sarcopenia and osteoporosis represent a growing public health problem. We studied the potential benefit of whole‐body vibration (WBV) training given a conventional or a high dose of daily vitamin D supplementation in improving strength, muscle mass, and bone density in postmenopausal women. In a 2 × 2 factorial‐design trial, 113 institutionalized elderly females aged over 70 years (mean age 79.6 years) were randomly assigned either to a WBV or a no‐training group, receiving either a conventional dose (880 IU/day) or a high dose (1600 IU/day) of vitamin D₃. The primary aim was to determine the effects of 6 months of WBV and/or vitamin D supplementation on isometric and dynamic strength, leg muscle mass, and hip bone mineral density (BMD). Additionally, the increase in 25‐hydroxyvitamin D [25(OH)D] levels between conventional and high‐dose supplementation was compared. After 6 months of treatment, dynamic muscle strength, hip BMD, and vitamin D serum levels improved significantly in all groups, whereas isometric strength and muscle mass did not change. When compared with no training, the WBV program did not result in additional improvements. When compared with 880 IU, a high dose of 1600 IU of vitamin D did result in higher serum vitamin D levels but did not result in additional improvements. In institutionalized women older than 70 years, the WBV training protocol tested is not more efficient in enhancing muscle mass, strength, and hip BMD compared with vitamin D supplementation. A higher dose of 1600 IU of vitamin D does not provide additional musculoskeletal benefit in this population compared with conventional doses. © 2011 American Society for Bone and Mineral Research.     

Assessment of the steady-state pharmacokinetic interaction between etravirine administered as two different formulations and tenofovir disoproxil fumarate in healthy volunteers

Objective

Two open‐label, randomized, cross‐over trials in healthy volunteers were conducted to investigate the pharmacokinetic interaction between etravirine and tenofovir disoproxil fumarate.

Methods

Etravirine was administered as either 800 mg twice a day (bid) (phase II formulation in Study 1) or 200 mg bid (phase III formulation in Study 2) for 8 days followed by a 12 h pharmacokinetic evaluation. After a minimum of 14 days washout, tenofovir disoproxil fumarate 300 mg once a day was administered for 16 days. Volunteers were randomized to receive co‐administration of etravirine with tenofovir disoproxil fumarate on either days 1–8 or days 9–16 followed by a 12 h pharmacokinetic evaluation for etravirine on day 8 or 16, respectively. Plasma and urine tenofovir concentrations were determined on days 8 and 16 over 24 h.

Results

The least square mean (LSM) ratio [90% confidence interval (CI)] for the area under the plasma concentration–time curve from 0 to 12 h (AUC_{12 h}) for etravirine co‐administered with tenofovir disoproxil fumarate vs. etravirine alone was 0.69 (0.61–0.79) and 0.81 (0.75–0.88) in Studies 1 and 2, respectively. The LSM ratio (90% CI) for the effect of etravirine on tenofovir AUC_{24 h} was 1.16 (1.09–1.23) in Study 1 and 1.15 (1.09–1.21) in Study 2.

Conclusions

These alterations are not considered clinically relevant for either drug and no dose adjustment is necessary when etravirine and tenofovir disoproxil fumarate are co‐administered.     

Interferon‐α treatment of female (NZW × BXSB)F1 mice mimics some but not all features associated with the Yaa mutation

Objective

Male (NZW × BXSB)F₁ mice develop antiphospholipid syndrome (APS) and proliferative glomerulonephritis that is markedly accelerated by the Yaa locus encoding an extra copy of Tlr7. Female (NZW × BXSB)F₁ mice with only 1 active copy of Tlr7 develop late‐onset glomerulonephritis but not APS. Because a major function of Toll‐like receptor 7 is to induce type I interferons (IFNs), our goal was to determine whether IFNα can induce or accelerate the manifestations of systemic lupus erythematosus (SLE) in female (NZW × BXSB)F₁ mice.

Methods

Eight‐week‐old female (NZW × BXSB)F₁ mice were injected with a single dose of adenovirus expressing IFNα. Mice were monitored for the development of thrombocytopenia and proteinuria. Sera were tested for anticardiolipin and anti‐Sm/RNP antibodies. Mice were killed at 17 or 22 weeks of age, and their kidneys and hearts were examined histologically and by immunohistochemistry. Spleen cells were phenotyped, and enzyme‐linked immunospot assays for autoantibody‐producing B cells were performed.

Results

IFNα markedly accelerated nephritis and death in female (NZW × BXSB)F₁ mice. A significant increase in spleen cell numbers associated with a striking increase in the number of activated B and T cells was observed. Marginal‐zone B cells were retained. IFNα‐induced increased titers of autoantibodies were observed, but thrombocytopenia was not observed. Cardiac damage was milder than that in male mice.

Conclusion

IFNα accelerates the development of renal inflammatory disease in female (NZW × BXSB)F₁ mice but induces only mild APS and does not induce thrombocytopenia. The effect of IFNα on SLE disease manifestations is strain dependent. These findings are relevant to our understanding of the physiologic significance of the IFN signature.