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OBJECTIVE: Phosphodiesterase-5 inhibitors, used to increase penile blood flow in erectile dysfunction patients, have recently been postulated to increase blood flow and flap survival in cutaneous flaps based on random blood supply. This study aims to investigate the phosphodiesterase-5 inhibitor tadalafil, administered orally, on random flap survival. METHODS: Modified McFarlane flaps measuring 8 cm × 2.5 cm were raised on the backs of 37 male Sprague-Dawley rats. Rats received were divided into a control group, a low-dose group (10 mg/kg tadalafil), and a high-dose group (20 mg/kg tadalafil). Treatment doses were administered once preoperatively and every 24 hours postoperatively for a total of 7 doses. On postoperative day 7 and 14, the area of flap survival was calculated and compared. RESULTS: All rats survived and thrived throughout the experimental period. Control group rats showed an average flap survival of 77% ± 11% at 7 days and 77% ± 9% at 14 days. Low-dose-group rats showed an average flap survival of 82% ± 10% at 7 days (P=0.21), and 81% ± 12% at 14 days (P=0.41). High-dose group rats showed an average flap survival of 81% ± 11% at 7 days (P = 0.45) and 80% ± 12% at 14 days (P = 0.53). Statistical analysis was performed using the Mann-Whitney test. CONCLUSIONS: Our results indicate a trend toward increased random-pattern flap survival with both high- and low-dose oral tadalafil in a rat model. Because this trend did not achieve statistical significance, further studies are warranted.

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BACKGROUND: We present a unique case of a cardiac transplant recipient who received an oversized heart. METHODS: To allow the chest to accommodate the organ, extensive resection of the bony chest wall was performed. As both pectoralis major myocutaneous flaps and omental transposition were insufficient to cover the wound, a chest rotational flap was chosen. RESULTS: The large size of the flap allowed us to cover the entire protuberant heart, and the excess soft tissue absorbed the pulsations from the heart without placing tension on the suture line. CONCLUSION: While the closure of complex sternal wounds can pose great challenges, the plastic surgeon possesses a variety of options including pectoralis, omental, rectus abdominus, latissimus dorsi as well as skin and subcutaneous flap closures to choose from.

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OBJECTIVE: To describe a case of gold sodium thiomalate use for the treatment of rheumatoid arthritis (RA) in a patient with hepatitis B. CASE SUMMARY: A 53-year-old Korean American woman with mild RA and chronic hepatitis B infection was treated for worsening RA symptoms with subcutaneous injections of gold sodium thiomalate for 21 months, with the dosage decreased from the initial 40 mg per week to 40 mg every 3 weeks after 51 weeks of successful treatment. She had undergone treatment for hepatitis B in the past with lamivudine; however, she had not received that medication for at least 1 year prior to initiating treatment with gold sodium thiomalate injections. During the treatment period she achieved remission of RA without a significant elevation of her liver enzyme levels or reactivation of hepatitis B. DISCUSSION: Two main factors influence drug product selection when considering the subset of RA patients with chronic hepatitis B infection: severity of liver function compromise and treatment status of chronic hepatitis B. Our patient did not demonstrate significant liver function compromise, but was not receiving viral suppressive treatment for hepatitis B; therefore, the use of many first-line nonbiologic disease-modifying antirheumatic drugs (DMARDs) was contra-indicated based on current guideline recommendations. Additionally, because the patient had refused viral suppressive therapy, there was great concern with the use of biological DMARDs and potential reactivation of hepatitis B. In the past, gold salts were the standard of care in treating RA until the development of the newer agents and there was some evidence that gold sodium thiomalate could be used with minimal risk of hepatotoxicity. CONCLUSIONS: Gold sodium thiomalate proved to be a safe and effective treatment option in a patient with RA and hepatitis B.

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In 2004, we published our 12-year experience with tissue transfer for deep sternal wound infection after median sternotomy, finding increased rates of reoperation for diabetic patients. Therefore, we decided to alter our treatment approach to diabetic patients to include sternal debridement followed by omental transposition. Eleven diabetic patients underwent omental transposition by our division during the study period. Hospital records were retrospectively reviewed to determine outcomes and complications. We found that diabetic patients treated after implementation of the new treatment approach were 5.4 times less likely to require reoperation for sternal wound management than were patients in the previous series, most of whom had been treated with pectoralis muscle flaps (95% confidence interval, 0.5- 50.5). By altering our treatment approach to use omental transposition as the initial surgical therapy, we were able to demonstrate a trend toward decreased need for flap revision in diabetic patients.

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BACKGROUND: Implant-based breast reconstruction is a popular option after mastectomy, but capsular contracture may detract from long-term outcomes. The authors have observed that breast implants covered with acellular dermal matrix (AlloDerm) are less likely to develop a capsule in the area where the implant is in direct contact with the acellular matrix. The authors tested this observation experimentally by comparing capsular formation around implants in the presence and absence of AlloDerm in primates. METHODS: Eight smooth-surfaced tissue expanders were implanted into eight African green monkeys. In four experimental animals, a sheet of AlloDerm was draped over the tissue expander so as to cover the implant. Four control animals underwent placement of a tissue expander only. Animals were killed after 10 weeks and specimens underwent histologic and immunohistochemical analysis. RESULTS: Hematoxylin and eosin staining of control specimens revealed the presence of a distinct layer of wavy, parallel arrays of collagen fibers consistent with capsule formation. Immunostaining identified abundant myofibroblasts, a profibrotic cell found in breast capsules. In the AlloDerm-covered specimens, no capsule layer was visible, and specimens stained weakly for myofibroblasts. The difference in myofibroblast staining intensity was statistically significant. CONCLUSIONS: The use of AlloDerm to partially enclose implants effectively prevented formation of a capsule in areas where AlloDerm contacted the implant at 10 weeks. Long-term studies will be required to determine whether this is a durable result that can be reproduced in humans.

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OBJECTIVE: To review clinical studies and other available literature regarding the development, pharmacology, toxicology, pharmacokinetics/pharmacodynamics, adverse effects, and place in therapy of bazedoxifene, a selective estrogen receptor modulator (SERM), currently in Phase III clinical trials for the treatment and prevention of postmenopausal osteoporosis. DATA SOURCES: A literature search was performed of PubMed (1966-February 2007), International Pharmaceutical Abstracts (1970-February 2007), Web of Science (1975-February 2007), Biological Abstracts (1926-2007), and Google Scholar (2001-February 2007) databases, using the search terms bazedoxifene, TSE-424, Indole-33, WAY-140424, selective estrogen receptor modulator, and SERM. In addition, product information was requested from the manufacturer, and www.clinicaltrials.gov was searched for unpublished Phase III clinical trials in progress. STUDY SELECTION AND DATA EXTRACTION: Articles on Phase I and II trials were selected for review, as well as articles discussing preclinical development of bazedoxifene. At the time of writing, no articles on Phase III trials were available for review. Abstracts of unpublished data were reviewed, as was information provided by the manufacturer. DATA SYNTHESIS: Bazedoxifene is a third-generation SERM currently in Phase III clinical trials. It has been found to act as an agonist on skeletal tissue, with bone turnover reduced by 20-25% with doses of 20 or 40 mg daily. In addition, bazedoxifene has been found to be an antagonist on breast tissue and uterine tissue, demonstrating inhibition of breast tissue proliferation and decreased endometrial stimulation as the dose is increased. CONCLUSIONS: Current literature suggests that bazedoxifene will likely be safe and effective when used in the treatment of postmenopausal osteoporosis. Completion of Phase III clinical trials will more fully elucidate the safety and efficacy profile of bazedoxifene, as well as more clearly define its place in therapy.

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Grapefruit is a healthy addition to a well-balanced diet. However, the fruit has been shown to affect the metabolism of many medications, increasing the risk of toxicity and adverse effects. Characteristics of oral medications that may interact with grapefruit include extensive metabolism through the intestinal cytochrome P450 3A4 system, low bioavailability, and a narrow therapeutic index. Prominent medications known to interact with grapefruit include statins, antiarrhythmic agents, immunosuppressive agents, and calcium channel blockers. There are equally effective alternatives to these drug classes that do not have the potential to interact with grapefruit. These alternative drugs may be substituted if a patient experiences or is at risk of a grapefruit-drug interaction. Patients also may choose to exclude grapefruit from their diets and consume other fruits, including other types of citrus, to avoid an interaction.

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For malaria to be transmitted, the Plasmodium falciparum parasite must invade an erythrocyte and undergo gametocytogenesis. When mature intraerythrocytic gametocytes are taken up in a blood meal by a mosquito they emerge as gametes and, once fertilized, continue to differentiate into infectious sporozoites. One of the major proteins associated with the surface of the parasite during gamete differentiation is Pfs230, a 360 kDa member of a family of P. falciparum proteins that contains a repeated cysteine motif domain. To characterize the role of different regions of Pfs230, the gene was disrupted by targeted integration and clones isolated that expressed distinct sections of Pfs230. Independent clones D1.356 a and b express the first 452 amino acids (aa) of Pfs230 and do not contain a cysteine motif domain, whereas clones D2.850 a and b express the first 950 aa, including the first cysteine motif domain. Although both sets of clones undergo gametogenesis and produce morphologically normal gametes, neither truncated Pfs230 is located on the surface of the gamete. In clones D1.356 a and b, the 452 aa Pfs230 is secreted into the parasitophorous vacuole and released as a soluble protein when the parasite emerges from the erythrocyte as a gamete. In marked contrast, the 950 aa form of Pfs230 expressed by clones D2.850 a and b is sequestered in a novel tubular compartment in the erythrocyte cytoplasm. This sexual-stage tubular intraerythrocytic compartment (STIC) is not recognized by antibodies specific for proteins associated with the parasitophorous vacuole membrane (Pfs16 or Exp-1) or Maurer's clefts (Pfsbp 1 or mAb LWL1) or intraerythrocytic asexual parasite proteins (PfEMP2 or HRP II).

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