Anomalous calcium secretion in rat ileum: role of paracellular pathway.

The mechanism of apparent calcium secretion by unstripped rat ileum in vitro has been investigated using mannitol and polyethylene glycol (mol wt 900) as markers for extracellular transepithelial flux. In the absence of electrochemical gradients between the mucosal and serosal bathing media in a modified Ussing chamber, net fluxes of both mannitol and polyethylene glycol were observed from serosa to mucosa in the presence of 11 mM D-glucose. Mucosal-to-serosal calcium flux reveals a significant cellular component, but serosal-to-mucosal calcium permeability is a linear function of mannitol permeability, suggesting an exclusively extracellular route. For the mucosal-to-serosal fluxes, inhibition of calcium flux by 1 mM N-ethylmaleimide results in a calcium-to-mannitol permeability ratio indistinguishable from that measured for serosal-to-mucosal flux. This evidence suggests that the apparent calcium secretion observed at 10 mM medium calcium is not the result of a cellular secretory mechanism. It is proposed that a hydrostatic driving force generated internal to the tissue but external to the cells results in net calcium secretion at calcium conentrations that saturate the cellular absorptive mechanism.     

Total Hip Arthroplasty is Less Painful at 12 Months Compared with Hemiarthroplasty in Treatment of Displaced Femoral Neck Fracture

Objectives The Displaced Femoral (neck fracture) Arthroplasty Consortium for Treatment and Outcomes (DFACTO) study compared total hip arthroplasty (THA) to hemiarthroplasty in the treatment of displaced femoral neck fractures. Design This study was designed as a prospective, randomized clinical trial. Setting The study was conducted in five US academic and private medical centers. Patients Patients were composed of independent, mentally competent individuals, >50 years old who suffered a displaced femoral neck fracture without existing arthritis at the hip. Forty-one patients were enrolled. Main outcome measures Functional outcomes and quality of life were assessed at 6 and 12 months post-fracture using the SF-36, Western Ontario and McMaster University Osteoarthritis Index (WOMAC), the Harris Hip Score, and the Timed “Up & Go” Test (TUG test). Results Groups were equivalent at baseline in terms of age, comorbid conditions, and functional status. At 6 months, there were no significant differences between the groups using the outcome measures or overall rates of complications. There was one dislocation in the THA group (5.8% of patients). At 12 months, the THA group reported significantly less pain (53.2 ± 10.2) than the hemiarthroplasty group (42.4 ± 11.5) using the SF-36 (p = 0.02). Using the TUG Test, we observed a greater proportion of THA patients remain functionally independent 1 year after surgery compared the hemiarthroplasty group (p = 0.08, controlling for age and sex). Conclusions These differences in pain and functional outcomes suggest THA is a viable treatment option for the active elderly displaced femoral neck fracture population. Level of Evidence: Level I: Randomized controlled trial. DFACTO Consortium: Christopher B. Michelsen, Catherine A. Compito, Justin Greisberg, Ohannes A. Nercessian, Howard A. Kiernan, Columbia University Medical Center, New York, NY; John F. Tilzey, Michael S. Thompson, Bernard A. Pfeifer, Lawrence M. Specht, Anthony H. Presutti, Lahey Clinic, Burlington, MA; Brian S. Parsley, Baylor College of Medicine, Houston, TX; Steven M. Teeny, Julian S. Arroyo, Dale L. Hirz, Alan B. Thomas, NorthWest Orthopaedic Institute, Tacoma, WA; Kevin L. Garvin, Todd Sekundiak, Matthew A. Morinino, Edward V. Ferhringer, Erik T. Otterberg, Univ. of Nebraska Medical Center, Omaha, NE.     

Urogenital aspects of actinomycosis.

Urogenital actinomycosis has always been a rare entity, limited to a few cases in any series. Treatment is highly successful but diagnosis remains elusive owing to low incidence, variable clinical picture, and biopsy and culture uncertainties. The general incidence of actinomycosis is believed to be decreasing in recent years but many infections may go undiagnosed while being suppressed or cured by conventional antibiotic therapy given for other resons. Our incidence of 4 cases of genitourinary and abdominal actinomycosis occurring in a 1-year period is highly unusual but the reasons remain speculative. Prior operation, abortion and induced infection via an intrauterine device were probably contributory. Whatever the case, if our experience is shared by others, genitourinary actinomycosis deserves more prominent diagnostic consideration in the future.     

Experience with the Small-Carrion penile prosthesis in the treatment of organic impotence.

Since certain animals are endowed with an os penis the concept of using penile implants was a natural development. Herein we report on our experience with the Small-Carrion penile prosthesis in 23 patients. The surgical technique is described as well as several examples of postoperative results. The major complication encountered was infection. All patients were able to accomplish coitus without significant difficulty. Proper patient selection and the attitude of the sexual partner constitute the major factors in the ultimate success or failure of the procedure.     

A small-molecule inhibitor of Bcl-XL potentiates the activity of cytotoxic drugs in vitro and in vivo

Inhibition of the prosurvival members of the Bcl-2 family of proteins represents an attractive strategy for the treatment of cancer. We have previously reported the activity of ABT-737, a potent inhibitor of Bcl-2, Bcl-X(L), and Bcl-w, which exhibits monotherapy efficacy in xenograft models of small-cell lung cancer and lymphoma and potentiates the activity of numerous cytotoxic agents. Here we describe the biological activity of A-385358, a small molecule with relative selectivity for binding to Bcl-X(L) versus Bcl-2 (K(i)'s of 0.80 and 67 nmol/L for Bcl-X(L) and Bcl-2, respectively). This compound efficiently enters cells and co-localizes with the mitochondrial membrane. Although A-385358 shows relatively modest single-agent cytotoxic activity against most tumor cell lines, it has an EC(50) of <500 nmol/L in cells dependent on Bcl-X(L) for survival. In addition, A-385358 enhances the in vitro cytotoxic activity of numerous chemotherapeutic agents (paclitaxel, etoposide, cisplatin, and doxorubicin) in several tumor cell lines. In A549 non-small-cell lung cancer cells, A-385358 potentiates the activity of paclitaxel by as much as 25-fold. Importantly, A-385358 also potentiated the activity of paclitaxel in vivo. Significant inhibition of tumor growth was observed when A-385358 was added to maximally tolerated or half maximally tolerated doses of paclitaxel in the A549 xenograft model. In tumors, the combination therapy also resulted in a significant increase in mitotic arrest followed by apoptosis relative to paclitaxel monotherapy.