History
In the 1950s, an Italian research company, Farmitalia Research Laboratories, began an organized effort to find anticancer compounds from soil-based microbes. A soil sample was isolated from the area surrounding the Castel del Monte, a 13th-century castle. A new strain of Streptomyces peucetius, which produced a red pigment, was isolated, and an antibiotic from this bacterium was effective against tumors in mice. Since a group of French researchers discovered the same compound at about the same time, the two teams named the compound daunorubicin, combining the name Dauni, a pre-Roman tribe that occupied the area of Italy where the compound was isolated, with the French word for ruby, rubis, describing the color. Clinical trials began in the 1960s, and the drug was successful in treating acute leukemia and lymphoma. However, by 1967, it was recognized that daunorubicin could lead to fatal cardiac toxicity.Researchers at Farmitalia soon discovered that changes in biological activity could be made by minor changes in the structure of the compound. A strain of Streptomyces was mutated using N-nitroso-N-methyl urethane, and this new strain produced a different, red-colored antibiotic. They named this new compound Adriamycin, after the Adriatic Sea, and the name was later changed to doxorubicin to conform to the established naming convention. Doxorubicin showed better activity than daunorubicin against mouse tumors, and especially solid tumors. It also showed a higher therapeutic index, yet the cardiotoxicity remained.Doxorubicin and daunorubicin together can be thought of as prototype compounds for the anthracyclines.
If the viability of an intrauterine pregnancy is uncertain, repeat ultrasonography coupled with laboratory measurement of progesterone and/or serial hCG can be helpful. The absence of either intrauterine or ectopic pregnancy on imaging is suggestive of a complete early pregnancy loss (if the pregnancy was previously seen on imaging) or a pregnancy of unknown location (if the pregnancy was not previously seen on imaging). Management
The management of early pregnancy bleeding depends on its severity and cause.Patients with significant first-trimester bleeding (more than spotting) should have a red blood cell antibody screen. Patients who are Rh-negative are usually given anti-D immune globulin to prevent RhD isoimmunization. People with significant blood loss who become hemodynamically unstable require rapid intervention. Early pregnancy loss can be treated with watchful waiting, medication, or uterine aspiration based on shared decision-making between the patient and provider. For those with incomplete abortion, watchful waiting is the recommended method as more than 90% of these patients will complete the process spontaneously within four week. Patients who decide on expectant management may experience more days of bleeding and longer completion time as compared to surgical management. Serious complications of watchful waiting are rare. Effective medical management entails 200 mg of oral mifepristone (Mifeprex) followed 24 hours later by 800 mcg of vaginally administered misoprostol. Bed rest and progesterone therapy have not been shown to increase the likelihood of a viable outcome.Ectopic pregnancy is treated with methotrexate therapy or surgery.