Soluble transforming growth factor-beta type III receptor gene transfection inhibits fibrous airway obliteration in a rat model of Bronchiolitis obliterans

Post-transplant bronchiolitis obliterans (BO) is characterized by fibroproliferation and fibrous obliteration of distal airways in chronically rejected lungs. In this study, using a rat heterotopic allogeneic tracheal transplant model of BO, we evaluated the expression of transforming growth factor-beta (TGFbeta) during the development of airway fibrous obliteration. Immunohistochemical analysis revealed TGFbeta staining in infiltrating mononuclear cells at Days 2 and 7, and in the fibrous tissues until Day 21. Soluble TGFbeta receptor type III (TGFBIIIR), by blocking TGFbeta binding to its membrane receptors, functions as a TGFbeta antagonist. To study the role of TGFbeta in the development of BO, adenoviral-mediated soluble TGFBIIIR gene transfection (5 x 10(9) particles) was performed topically at the site of transplant on Day 5 after transplantation, which leads to inhibition of fibrous airway obliteration. In contrast, empty vector gene delivered through intramuscular injection, or given locally at Days 0 or 10 after tracheal transplantation had no significant effect. These results suggest that TGFbeta expressed in the allografts plays a pivotal role in the pathogenesis of BO. Soluble TGFBIIIR may competitively inhibit TGFbeta activity locally. Adenoviral-mediated soluble TGFBIIIR gene transfection should be further explored as a potential therapeutic modality for BO and other conditions involving chronic fibrosis.     

Management of metabolic complications of therapy

Considerable efforts are underway to define effective strategies for the treatment of metabolic complications of HIV therapy. Clearly these problems dominate the overall approach to treatment of HIV infection in the settings where antiretroviral agents are accessible. While progress has been made it has been slow, and accompanied by disappointments. There are currently no effective treatments for lipoatrophy, and while treatments for dyslipidemia have been described, in most cases the improvement is incomplete. While these efforts must continue it is hoped that a new focus on prevention of metabolic complications will begin to emerge in the year ahead.     

The effect of proteasome inhibitors on mammalian erythroid terminal differentiation

OBJECTIVES: Murine erythroblasts infected with the anemia-inducing strain of Friend virus (FVA cells) terminally differentiate to the reticulocyte stage after 48 hours of culture in vitro in response to erythropoietin (EPO). The objective of this study was to determine the possible role of proteasome-mediated proteolysis during the terminal differentiation of FVA cells. MATERIALS AND METHODS: The proteasome inhibitors MG132 and lactacystin were used to perturb the normal function of proteasomes during terminal differentiation. Effects of proteasome inhibitors on terminal differentiation were quantitated by evaluation of cellular morphology after benzidine staining and by Western blot analyses. RESULTS: Treatment of EPO-stimulated FVA cells with lactacystin or MG132 at later periods of culture increased accumulations of nuclear and cytosolic ubiquitinated proteins and decreased nuclear extrusion to less than 40% of controls. CONCLUSIONS: Our results suggest that the proteasomal degradation of ubiquitinated proteins plays an important role in the enucleation of mammalian erythroblasts.     

Guidance of percutaneous pulmonary biopsies with real-time CT fluoroscopy

OBJECTIVE: Clinical evaluation of computed tomography (CT) fluoroscopy and comparison with conventional CT guidance for monitoring of percutaneous pulmonary biopsy procedures. METHODS: Twenty CT-guided pulmonary biopsy procedures were conducted. The interventions have prospectively been performed either with CT fluoroscopy or with conventional CT guidance. About 120 kV and 50 mA with a frame-rate of eight images per second were used for CT fluoroscopy. Number of pleural needle passages, procedure times, radiation doses and histologic results were analyzed separately for both methods. RESULTS: Compared with conventional CT guidance, CT fluoroscopy was associated with less pleural needle passages (1.8+/-0.6 vs. 1.1+/-0.3; P=0.003, t-test) and procedure times were shorter than for conventional CT guidance (12.7+/-2.2 min vs. 26.7+/-16.4 min; P=0.02). Analysis of estimated patient related radiation exposure and histologic outcome showed no significant difference between conventional and fluoroscopic CT-guided procedures (P>0.05). CONCLUSION: CT fluoroscopy facilitates guidance of percutaneous pulmonary biopsy procedures. Compared with conventional CT assistance, procedure times are decreased and less pleural needle passages are required. While patient-related radiation exposure is similar, operator-related radiation exposure remains a disadvantage associated with CT fluoroscopy.     

Outbreak of head pediculosis during SFINCSS-99 isolation experiment

This short case report presents the development and treatment of a head lice outbreak during a space simulation experiment. The confinement experiment was conducted from July 1999 to March 2000 at the State Research Center of the Russian Federation Institute for Biomedical Problems in Moscow. Following a symptom period of up to 9 wk before diagnosis and treatment, 3 wk of treatment were required to remove all nits from those infected. Recommendations are made with regard to prevention of such infections during space missions. Treatment altered performance and comfort of crews, took time out of other duties, and even affected relations between crewmembers. The case is made for the development of a public health agenda in space research and medical space programs.     

The pancake phenomenon contributes to the inaccuracy of margin assessment in patients with breast cancer

BACKGROUND: To determine the effect on margin evaluation for patients with breast cancer, we prospectively quantified the "flattening" of the breast specimen after surgical removal. METHODS: The volume and height of 100 consecutive breast biopsy specimens were recorded independently by the operating surgeon and the pathologist. Five factors were analyzed that were thought to contribute to changes in specimen dimensions: patient age, breast tissue density, mammographic lesion type, specimen size, and the use of compression during specimen radiography. RESULTS: After surgical removal, mean volume and height of the breast specimens decreased from 46 cm(3) to 29 cm(3) (30%) and from 2.6 cm to 1.4 cm (46%), respectively. Flattening of the breast specimens occurred in all subgroups studied. CONCLUSIONS: Breast specimens are flattened after surgical removal, losing almost 50% of their original height. This "pancake" phenomenon has important implications for the accuracy of margin analysis.     

How could management of rectoceles be optimized?

A posterior vaginal wall prolapse, also known as a rectocele, is a common condition and is an outpouching of the posterior vaginal wall and anterior rectal wall into the lumen of the vagina.1-5 Although more common in parous women, rectoceles of over 1 cm in size have been demonstrated in over 40% of nulliparous women. As rectoceles may be asymptomatic, their true prevalence is not clear. Many women with rectoceles present to their gynaecologist who may not ascertain any anorectal symptoms or perform a rectal examination. Conversely, colorectal surgeons often disregard a vaginal examination.6 Conventionally, gynaecologists have managed rectoceles, but increasingly colorectal surgeons are involved because of the prevalence of anorectal symptoms. There are many surgical techniques for the management of a symptomatic rectocele. There is, however, little data to suggest which is the most effective technique, or whether specific techniques are more appropriate in certain circumstances.7