Rescue therapy with tacrolimus in a patient with toxic megacolon

BACKGROUND: Toxic megacolon is a life-threatening complication most commonly observed in patients with ulcerative colitis or Crohn's disease that is characterized by total or segmental nonobstructive colonic dilatation of at least 6 cm on plain abdominal films associated with systemic toxicity. CASE REPORT: We report an unusual case of fulminant steroid-refractory ulcerative colitis complicated by toxic megacolon treated successfully with the immunosuppressant tacrolimus. CONCLUSION: Tacrolimus administration induced clinical remission and bridged the time interval, until the standard immunosuppressant azathioprine could maintain clinical remission, thereby avoiding eminent emergency colectomy.     

Plasma lidocaine concentrations after local anesthesia of the groin for cardiac catheterization.

This study aimed to investigate serum lidocaine concentrations after subcutaneous infiltration of the groin for cardiac catheterization. One hundred twenty-six patients for planned heart catheterization received five different dosages (5-25 ml) of lidocaine 2% for local anesthesia of the groin in a randomized manner. All of them received an arterial sheath and 13 received both an arterial sheath and a venous sheath for right heart catheterization. Blood samples were taken before as well as 15, 30, and 120 min after subcutaneous application of the drug. Although in 33 patients with an arterial sheath (no venous sheath) excessive doses of lidocaine 2% (20-25 ml) were used, neither symptoms of intoxication nor toxic plasma levels were observed. However, in patients receiving an additional venous sheath, toxic plasma levels were obtained in a third of the cases. One of them showed symptoms of intoxication.     

Ammonia-oxidizing bacteria respond to multifactorial global change

Recent studies have demonstrated that multiple co-occurring global changes can alter the abundance, diversity, and productivity of plant communities. Below ground processes, often mediated by soil microorganisms, are central to the response of these communities to global change. Very little is known, however, about the effects of multiple global changes on microbial communities. We examined the response of ammonia-oxidizing bacteria (AOB), microorganisms that mediate the transformation of ammonium into nitrite, to simultaneous increases in atmospheric CO2, precipitation, temperature, and nitrogen deposition, manipulated on the ecosystem level in a California grassland. Both the community structure and abundance of AOB responded to these simulated global changes. Increased nitrogen deposition significantly altered the structure of the ammonia-oxidizing community, consistently shifting the community toward dominance by bacteria most closely related to Nitrosospira sp. 2. This shift was most pronounced when temperature and precipitation were not increased. Total abundance of AOB significantly decreased in response to increased atmospheric CO2. This decrease was most pronounced when precipitation was also increased. Shifts in community composition were associated with increases in nitrification, but changes in abundance were not. These results demonstrate that microbial communities can be consistently altered by global changes and that these changes can have implications for ecosystem function.     

PSA bounce after <Superscript>125</Superscript>I-brachytherapy for prostate cancer as a favorable prognosticator

Background

Permanent low-dose-rate brachytherapy (BT) with iodine 125 is an established curative treatment for localized prostate cancer. After treatment, prostate-specific antigen (PSA) kinetics may show a transient rise (PSA bounce). Our aim was to investigate the association of PSA bounce with biochemical control.

Patients and methods

Patients treated with BT in Switzerland were registered in a prospective database. Only patients with a follow-up of at least 2 years were included in our analysis. Clinical follow-up and PSA measurements were assessed after 1.5, 3, 6, and 12 months, and annually thereafter. If PSA increased, additional follow-up visits were scheduled. Cases of PSA bounce were defined as a rise of at least 0.2 ng/ml above the initial PSA nadir with a subsequent decline to or below the initial nadir without treatment. Biochemical failure was defined as a rise to nadir +?2 ng/ml.

Results

Between March 2001 and November 2010, 713 patients with prostate cancer undergoing BT with at least 2 years of follow-up were registered. Median follow-up time was 41 months. Biochemical failure occurred in 28 patients (3.9?%). PSA bounce occurred in 173 (24.3?%) patients; only three (1.7?%) patients with PSA bounce developed biochemical failure, in contrast to 25 (4.6?%) patients without previous bounce (p?<?0.05). The median time to bounce was 12 months, the median time to biochemical failure was 30 months. The median bounce increase was 0.78 ng/ml. Twenty-eight patients with bounce (16.5?%) had a transient PSA rise of +?2 ng/ml above the nadir.

Conclusion

In most cases, an early increase in PSA after BT indicates PSA bounce and is associated with a lower risk of biochemical failure.

     

Scaffold attachment region-containing retrovirus vectors improve long-term proviral expression after transplantation of GFP-modified CD34+ baboon repopulating cells

Sustained high-level proviral expression is important for clinical applications of gene therapy. Genetic elements including the beta-interferon scaffold attachment region (SAR) have been shown to improve transgene expression in hematopoietic cells. We hypothesized that SAR elements might improve expression and allow the preselection of successfully transduced cells. Thus, we transplanted green fluorescent protein (GFP)-selected cells, half of which had been transduced with either SAR or non-SAR-containing retrovirus vectors, into 3 animals. All animals showed delayed engraftment compared with historic controls (28 vs 15.5 days). GFP marking was seen at levels up to 8% but declined over the first 6 weeks. Importantly, fluorescence intensity was 2- to 9-fold increased in progeny of SAR versus non-SAR vector-modified cells in all hematopoietic lineages for the duration of follow-up (6-12 months). In conclusion, the use of SAR-containing vectors improved transgene expression in hematopoietic repopulating cells, which may obviate the need for multicopy integration to achieve high-level expression and reduce the risk for insertional mutagenesis.     

Immune response to capsular polysaccharide and surface proteins of Streptococcus pneumoniae in patients with invasive pneumococcal disease

The immune response to pneumococcal capsular polysaccharides (CPSs) and to the pneumococcal surface proteins cell wall-associated serine proteinase A (PrtA), pneumococcal surface protein A (PspA), and Streptococcus pneumoniae pullulanase A was evaluated in 45 patients with invasive pneumococcal disease compared with healthy adults. In serum from patients with meningitis and pneumonia, CPS antibody levels were low, compared with healthy adults; antibody levels did not differ between groups and did not change between phases. Levels of immunoglobulin G directed against the investigated pneumococcal surface proteins in patients with invasive pneumococcal disease were in the same range as in healthy adults. However, median PrtA and PspA antibody levels tended to increase during early convalescent phase. Low levels of CPS antibody, rather than of antibodies directed against the pneumococcal surface proteins, may predispose to invasive pneumococcal infection.