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.     

Primary hypothyroidism presenting as ovarian tumor and precocious puberty in a prepubertal girl.

We report a case of a prepubertal girl with juvenile primary hypothyroidism presenting as ovarian cysts and precocious puberty. The 7-year-old female was referred to our clinic because of a pelvic/abdominal mass and vaginal bleeding. Besides these findings, on physical examination we noticed the thyroid gland globally increased and the presence of secondary sexual characteristics. Based upon the clinical profile and investigations, the patient was diagnosed with juvenile primary hypothyroidism due to autoimmune thyroiditis. The cysts and precocious puberty resolved spontaneously after the simple replacement of thyroid hormone. It is important to bear in mind hypothyroidism in cases of girls presenting ovarian cysts and precocious puberty in order to avoid unnecessary surgery on the ovaries.     

Rhabdomyolysis: a manifestation of cyclobenzaprine toxicity

A case of cyclobenzaprine (flexeril) overdose and the resultant rhabdomyolysis is presented. A review of the range of clinical toxicity, management of overdose is described. The similarity of cyclobenzaprine to the tricyclic antidepressant class is emphasized; this report attempts to disseminate related information on this commonly prescribed centrally acting muscle relaxant.     

Vaginal stenosis in patients treated with radiotherapy for carcinoma of the cervix

The aim of our study was to determine the incidence, timing, and severity of vaginal stenosis in patients with carcinoma of the cervix who had received pelvic and/or vaginal radiotherapy as part of their treatment. We also sought to determine if there were any predisposing factors for the development of stenosis. A retrospective chart review was undertaken for all the patients diagnosed with carcinoma of the cervix between January 1, 1990, and December 31, 2000 and treated with pelvic and/or vaginal radiation at Westmead Hospital. Since January 1, 1990, data regarding vaginal stenosis has been prospectively recorded on all the patients. Data collected included patient demographics, stage of disease, treatments administered, and incidence, timing, and severity of vaginal stenosis. One hundred and eighty-eight patients were treated. Mean age was 58.6 years. Thirteen percent of patients had stage IB disease, 45% had stage II disease, 39.5% had stage III disease, and 1.5% had stage IV disease. One hundred and seventy-nine patients returned for follow-up, and data regarding vaginal toxicity were available in 98%. Twenty-seven percent had grade 1 toxicity (partial stenosis or shortening but not complete occlusion), and 11% had grade 2 (complete occlusion). Stenosis of any grade was noted at a mean of 9.6 months and median of 7.5 months (range, 26 days-5.6 years) from completion of treatment. The only prognostic factor associated with increased risk of stenosis was age greater than 50 years (odds ratio 2.26). Vaginal stenosis is a common complication of pelvic and vaginal radiotherapy, occurring in 38% of patients. Stenosis occurs most often in the first year after treatment. Patients over the age of 50 are most at risk.     

Angiotensin Converting Enzyme Inhibitors: Animal Experiments Suggest a New Pharmacological Treatment for Alcohol Abuse in Humans

The prevalence of heavy alcohol consumption is a major problem of increasing proportions throughout the world. Although alcohol sensitizing drugs and more recently serotonin uptake inhibitors are drug interventions with some following, their long term beneficial consequences have yet to be demonstrated. In recent years, we have demonstrated that manipulating activity in the renin-angiotensin system will dramatically alter voluntary alcohol consumption in rats. Based on these findings, the present study evaluated the ability of a class of drugs known as the angiotensin converting enzyme inhibitors to reduce voluntary alcohol drinking in laboratory animals. These drugs prevent the conversion of angiotensin I to angiotensin II. They have been licensed for use in Europe and North America and are indicated in the treatment of hypertension. Our experiments showed that both captopril (Capoten, Squibb) and enalapril (Vasotec, Merck Sharpe & Dohme) can reduce alcohol drinking in both normotensive and hypertensive animals regardless of whether the pattern of intake is in a bout or of a less exaggerated nature. Furthermore, this change in alcohol intake can occur without concomitant changes in blood pressure, plasma renin activity, overall fluid balance, or the distribution and metabolism of alcohol. Taken together these findings suggest that the angiotensin converting enzyme inhibitors should be evaluated in a clinical setting for they may prove to be a useful new treatment or treatment adjunct for alcohol abuse in humans.