IFN-alpha1,8 inhibits tumor-induced angiogenesis in murine angiosarcomas.

Interferon-alpha (IFN-alpha) has proved effective in the treatment of hemangiomas, hemangioblastomas, and Kaposi's sarcoma. To investigate the ability of IFNs to inhibit angiosarcoma, we used two transformed murine endothelial cell lines that form angiosarcomas in vivo. SVR and MS1-VEGF cell lines express oncogenic H-ras or vascular endothelial growth factor (VEGF), respectively. IFN-alpha1,8, which is active against murine and human cells, inhibited SVR and MS1-VEGF proliferation in vitro by 40% at 10(3) U/mL (p = 0.028). In vivo, IFN-alpha1,8 inhibited SVR tumor volume by 71% (p = 0.047) and MS1-VEGF volume by 79% (p = 0.003). Tumor-induced angiogenesis was decreased in SVR tumors by 52% (p = 0.005) and in MS1-VEGF tumors by 58% (p = 0.001). Sera from IFN-alpha1,8-treated mice bearing either SVR or MS1-VEGF tumors demonstrated a 5-fold increase in IP-10/CXCL10 (p = 0.001), an IFN-induced antiangiogenic protein. Both recombinant IP-10 and IFN-alpha1,8 inhibited human umbilical vein endothelial cell (HUVEC) vessel formation in the fibrin gel assay, a three-dimensional culture model of angiogenesis, by 56% at 25 ng/mL and 50% at 1.2 ng/mL, respectively (p < 0.001). An IP-10 blocking antibody restored vessel formation to 80% of untreated controls (p = 0.001). Given the magnitude of the in vivo response, these data suggested that the antitumor effects of IFN-alpha1,8 were likely mediated through angiogenesis inhibition rather than solely by direct inhibition of tumor cell proliferation.     

Leishmania identification by PCR of Giemsa-stained lesion imprint slides stored for up to 36 years

This study examined the ability of PCR to amplify Leishmania DNA, stored on Giemsa-stained slides, from American cutaneous leishmaniasis (ACL) patients. In total, 475 slides stored for up to 36 years were obtained from an outpatient clinic in a Brazilian ACL-endemic region, and Leishmania DNA was amplified from 395 (83.2%) of the DNA samples using primers specific for the minicircle kinetoplast DNA. Restriction fragment length polymorphism analysis of these amplicons demonstrated that Leishmania (Viannia) braziliensis was the only species present in these samples. The results demonstrated that archived Giemsa-stained slides can provide a Leishmania DNA source for performing clinical and epidemiological studies of leishmaniasis.     

Pedicled deltoid hatchet flap for treatment of pressure sore at the shoulder

Whereas decubitus ulcer in the back or hip region is a common entity in plegic or elderly patients, the occurrence in the lateral shoulder region is seldom seen. However, resulting from continuous lateral decubitus positioning or limited compliance by the patient, pressure sores may occur in almost any region of the body, but predominately, they arise in acral zones with underlying bone prominences. The deltoid area is such an anatomically critical region, especially if the underlying deltoid muscle is paralyzed. The transposition of a pedicled deltoid flap, slightly modified as a hatchet flap, is described for cover of a decubitus ulcer in the deltoid region in a paraplegic male. Although utilization of the deltoid flap as a free flap is an established procedure for selected indications [Russell et al. (1985) Extremity reconstruction using the free deltoid flap. Plast Reconstr Surg 76:586–595, Serafin D (1996) The deltoid flap. In: Serafin D (ed) Atlas of microsurgical composite tissue transplantation, chapter 19. Saunders, Philadelphia, PA, pp 153–159, Wang et al. (2003) The free deltoid flap: microscopic anatomy studies and clinical application to oral cavity reconstruction. Plast Reconstr Surg 112:404–411], transposition as a pedicled flap, to the best of our knowledge, has not been previously described in the available literature.     

Hormonal and Metabolic Disorders of Human Immunodeficiency Virus Infection and Substance Abuse

There are an estimated 200 million users of an illicit drug in the world today. In addition, an estimated 40 million people are infected with the human immunodeficiency virus (HIV) and an estimated 180 million people are infected with the hepatitis C virus (HCV). Both the use of an illicit drug and the co-occurrence of infections are associated with a multitude of medical and health consequences including hormonal and metabolic disorders. Thus, the National Institute on Drug Abuse (NIDA), a part of the National Institutes of Health (NIH) hosted a workshop on hormonal and metabolic disorders of HIV among substance abusers. A number of clinicians and scientists participated and discussed a wide range of issues concerning hormones, nutrition and metabolic complications in HIV and substance abuse. Their observations and the recommendations they made for future research are presented in these proceedings. The readers are encouraged to contact the NIH staff (JK, FV) for technical guidance and programmatic priorities on the subject and directly contact the individual authors for collaborations.     

Treatment of dysfunctional uterine bleeding in the perimenopause: the effects of adding combined estradiol/norethisterone acetate therapy to goserelin acetate treatment--a randomized, placebo-controlled, double-blind trial.

OBJECTIVE: To assess the effects of adding combined estradiol/norethisterone acetate therapy (CENT) to goserelin acetate treatment (GA) of dysfunctional uterine bleeding (DUB) in perimenopausal women. METHODS: In a randomized, placebo-controlled, double-blind trial followed by an open follow-up study, 31 perimenopausal women with DUB were recruited from gynecological outpatient departments of two Dutch hospitals and randomized for treatment with either GA/placebo or GA/CENT for 6 months followed by 18 months of GA/CENT for all. The main outcome measures were abdominal pain, number of bleeding days, double-layer endometrial thickness (DET), Greene climacteric score (GCS), visual analog scale for well-being, bone mineral density (BMD) and mammographic density (BI-RAD score). RESULTS: Abdominal pain, number of bleeding days and DET decreased in both groups, the between-group difference in decrease not being statistically significant. GCS initially showed significant improvement in the GA/CENT group. BMD decreased significantly in the GA/placebo group (-4.1%) compared with the GA/CENT group (-0.3%). Another 18 months of GA/CENT did not result in a lasting difference in BMD between groups. BI-RAD scores did not differ significantly between or within the two groups. CONCLUSIONS: Adding CENT to GA treatment for DUB in perimenopausal women initially prevented BMD loss and improved climacteric complaints, while having no negative impact on vaginal bleeding, abdominal pain or BI-RAD scores. However, prolonged treatment did not result in a lasting prevention of bone loss.     

Symptomatic osteoradionecrosis of pelvic bones in patients with gynecological malignancies—result of a long-term follow-up

The aim of this study was to assess the incidence and risk factors of pelvic fractures as a result of radiation therapy in women with gynecological cancer. We retrospectively reviewed 3530 female patients treated at our institute between 1980 and 1998 with megavoltage radiation with or without brachytherapy for cancer in the pelvic area. Eligible were patients with vulvar, vaginal, cervical, endometrial, and fallopian tube cancer. Median follow-up was 88 months (range 0-240). Emphasis was put on treatment-related and patient-related risk factors. Of the eligible 3155 patients, 15 developed symptomatic bone fracture caused by osteoradionecrosis, which makes an overall incidence of 0.44% The diagnosis was based on anamnesis, clinical course, and X-ray or computed tomography images. Median time of onset was 44 months (range 6-197). All patients had pain as the first symptom. The only independent predictive factor for developing osteoradionecrosis seemed to be preexistent osteoporosis. Other risk factors that are related to osteoporosis include higher age, postmenopausal status, or steroid treatment. We did not find any significant treatment-related predictive factor for pelvic osteoradionecrosis. Patients with osteoporosis are probably at the highest risk for developing osteoradionecrotic fractures after pelvic radiotherapy. More studies are needed to find out other endogenous predictive factors.