Background-Although pulmonary infiltrates are common in bone marrow transplant recipients and add significantly to the morbidity and mortality of this group of patients, there is uncertainty as to the most appropriate investigation and a lack of information on the effects of investigations on management and outcome. Methods-All bone marrow transplant recipients from one institution referred for respiratory investigation between 1982 and 1990 were reviewed. Results-Of 204 bone marrow transplant recipients 27 developed pulmonary infiltrates which failed to respond to broad spectrum antibiotics. All were examined by bronchoscopy and bronchoalveolar lavage. A specific diagnosis was made in 20 cases, 17 with an infective cause and three with a non-infective aetiology. In 17 of the 27 episodes these investigations led to a positive change in treatment, but in only five did these changes result in patient survival beyond one nionth. Eighteen of the 20 deaths were due to progressive respiratory failure of an infective aetiology in 14 and non-infective in four.Conclusions-Bronchoscopy and bronchoalveolar lavage are effective in establishing a diagnosis, but the impact on overall survival is disappointingly poor.

Purpose: To retrospectively describe the clinical characteristics, management, and outcomes of a series of patients with solitary fibrous tumor (SFT) of the orbit and to evaluate signal transducer and activator of transcription 6 (STAT6) as a diagnostic marker. Methods: Review of a retrospective, noncomparative, consecutive series of patients treated at a single institution with a histopathologic diagnosis of SFT. Demographic, clinical, and imaging data were collected, and paraffin-embedded tissue sections were stained to evaluate for the presence of STAT6 and other pertinent markers. Results: Twenty-one patients were identified. Most presented with painless progressive proptosis or eyelid swelling for less than 6 months. Imaging revealed well-circumscribed, firm, variably vascular contrast-enhancing lesions with low to medium reflectivity on ultrasound. Four tumors were histopathologically malignant. All tumors were primarily excised, and 1 patient required exenteration. Two patients were treated with adjuvant radiation therapy. Six patients had recurrent disease of which 3 underwent repeat excision, and 2 were observed. No metastatic disease or attributable deaths were observed. All lesions with available tissue stained positively for both CD34 and STAT6. Conclusion: This is the largest single institution case series of orbital SFT with clinicopathologic correlation and the largest series to confirm the presence of STAT6 in orbital lesions. The management of SFT remains challenging due to unpredictable tumor behavior, and complete excision is the generally recommended treatment. It remains unclear whether a subset of asymptomatic patients with histopathologically benign disease can be durably observed without negative sequelae.

Blessing NW, Blount MA, Sands JM, Martin CF, Klein JD. Urea transporters UT-A1 and UT-A3 accumulate in the plasma membrane in response to increased hypertonicity. Am J Physiol Renal Physiol 295: F1336 -F1341, 2008. First published August 20, 2008 doi:10.1152/ajprenal.90228.2008.-The UT-A1 and UT-A3 urea transporters are expressed in the terminal inner medullary collecting duct (IMCD) and play an important role in the production of concentrated urine. We showed that both hyperosmolarity and vasopressin increase urea permeability in perfused rat terminal IMCDs and that UT-A1 and UT-A3 accumulate in the plasma membrane in response to vasopressin. In this study, we investigated whether hyperosmolarity causes UT-A1 and/or UT-A3 to accumulate in the plasma membrane or represents a complimentary stimulatory pathway. Rat IMCD suspensions were incubated in 450 vs. 900 mosM solutions. We biotinylated the IMCD surface proteins, collected, and analyzed them. Membrane accumulation was assessed by Western blotting of the biotinylated protein pool probed with anti-UT-A1 or anti-UT-A3. We studied the effect of NaCl, urea, and sucrose as osmotic agents. Membraneassociated UT-A1 and UT-A3 increased relative to control levels when either NaCl (UT-A1 increased 37 Ϯ 6%; UT-A3 increased 46 Ϯ 13%) or sucrose (UT-A1 increased 81 Ϯ 13%; UT-A3 increased 60 Ϯ 8%) was used to increase osmolarity. There was no increase in membrane UT-A1 or UT-A3 when urea was added. Analogously, UT-A1 phosphorylation was increased in NaCl-and sucrose-but not in urea-based hyperosmolar solutions. Hypertonicity also increased UT-A3 phosphorylation. We conclude that the increase in the urea permeability in response to hyperosmolarity reflects both UT-A1 and UT-A3 movement to the plasma membrane and may be a direct response to tonicity. Furthermore, this movement is accompanied by, and may require, increased phosphorylation in response to hypertonicity.renal; osmolality; concentrating mechanism; trafficking THE INNER MEDULLA is often hypertonic, especially during antidiuresis, when plasma vasopressin levels are high (12). Vasopressin stimulates urea transport across perfused rat terminal inner medullary collecting ducts (IMCD) (13). Urea transport is also stimulated by hyperosmolarity (resulting from addition of NaCl) in the absence of vasopressin and is further stimulated in the presence of vasopressin (14). While both vasopressin and hyperosmolarity stimulate urea transport, they do so through different second messenger pathways; vasopressin acts by increasing cAMP while hyperosmolarity acts by increasing intracellular calcium but does not increase cAMP (6, 18).UT-A1 is the major urea transport protein expressed in the IMCD (15). Vasopressin increases urea flux in Madin-Darby canine kidney (MDCK) cells that are stably transfected with UT-A1 (4). In rat IMCD suspensions, vasopressin increases both UT-A1 phosphorylation and UT-A1 plasma membrane accumulation (8). Vasopressin stimulation of UT-A1 phosphorylation can be blocked by the protein kinase A (PKA) inh...

PurposeWe characterize the effect of bimatoprost on orbital adipose tissue in thyroid-associated orbitopathy (TAO) with clinicopathologic correlation.MethodsOrbital adipose-derived stem cells (OASCs) from types 1 and 2 TAO and control patients with and without exposure to 1 μm bimatoprost were examined via immunohistochemistry, RT-PCR, and Western blot for cell viability, migration capacity, lipid content, adipocyte morphology, mitochondrial content, and levels of adipogenic markers. A retrospective chart review was performed for clinicopathologic correlation. In mice, optical coherence tomography and pattern electroretinography were performed at baseline and at 1 month following a retrobulbar injection of bimatoprost, followed by orbital exenteration for histopathologic examination.ResultsTypes 1 and 2 TAO-derived cells had a significantly higher migration capacity and lipid content than those of healthy controls. With the addition of bimatoprost, types 1 and 2 TAO and control adipocytes exhibited a significant decrease in lipid content with morphologic transformation into smaller and multilocular lipid droplets, and an increase in mitochondrial load and UCP-1 expression consistent with an increase in brown adipose tissue turnover. Retrobulbar injection of bimatoprost in mice did not alter the gross morphology, retinal thickness, or ganglion cell function in vivo.ConclusionsBimatoprost inhibits adipogenesis in OASCs and upregulates pathways involved in the browning of adipocytes. Furthermore, retrobulbar injection of bimatoprost is tolerated without immediate adverse effects in mice. Our results suggest a potential future application of prostaglandin analogues in the treatment of TAO.