Synthesis of an orthogonally protected precursor to the glycan repeating unit of the bacterial cell wall.

[reaction: see text]. A synthesis of stereochemically pure and orthogonally protected N-acetyl-(2-deoxy-2-aminoglucopyranosyl)-beta-[1,4]-N-acetylmuramyl (NAG-NAM) monopeptide (2), the glycopeptide core of lipid II and of the bacterial cell wall repeating unit, is reported.

Ovarian cancer in a woman previously diagnosed with endometriosis and an extremely high serum CA-125 level.

PURPOSE: Follow-up of a woman with a serum CA-125 level > 1000 U/mL where laparoscopy only found endometriosis. METHODS: Case report-- re-evaluation several years later. RESULTS: Extensive clear-cell carcinoma of ovary with metastases leading to death. CONCLUSION: This case suggests that bilateral oophorectomy should be performed in women not desiring any more children if the serum CA- 125 level is very high even if only endometriosis is found initially.

The total synthesis of lipid I.

A total synthesis of lipid I (4), a membrane-associated intermediate in the bacterial cell wall (peptidoglycan) biosynthesis pathway, is reported. This highly convergent synthesis will enable further studies on bacterial resistance mechanisms and may provide insight toward the development of new chemotherapeutic agents with novel modes of action.

Phase II study of mifepristone (RU486) in refractory ovarian cancer.

OBJECTIVE: A phase II study of Mifepristone (RU486) was conducted in patients with ovarian cancer whose tumors were resistant to cisplatin and paclitaxel, alone or in combination. PATIENTS AND METHODS: Forty-four patients were accrued into this study. All had ovarian cancer that had become resistant to cisplatin and paclitaxel. Patients received Mifepristone 200 mg orally on a daily basis. Patients were followed by tumor size or CA-125 levels when there was no measurable disease. A dose reduction of Mifepristone was to occur in the event of grade 3/4 hematologic, GI, or liver toxicity, creatinine >2.5%, and grade 4 peripheral neuropathy. RESULTS: Thirty-four patients were evaluable for response. Nine (26.5%) of these patients had a response to Mifepristone. Three(9%) patients had a complete response, and six (17.5%), a partial response. The response of one patient in each group was measured by CA-125 levels while the remainder had measurable disease. The response lasted 1 to 4 months in all but one patient. One patient continues to respond after more than 3 years. The major toxic effect was a rash and this was the major reason patients were removed from the study. CONCLUSION: Mifepristone has activity against ovarian cancer resistant to cisplatin and paclitaxel. The drug is well tolerated. Further studies need to be performed when this drug becomes more widely available in the United States.

Post-hysterectomy fallopian tube carcinoma presenting with a positive Papanicolaou smear.

BACKGROUND: Fallopian tube carcinoma is a rare gynecologic malignancy. The majority of women present with vaginal bleeding and have advanced disease. CASE: A 76-year-old woman presented 34 years after vaginal hysterectomy with a routine Papanicolaou smear showing adenocarcinoma. Rectovaginal examination was remarkable for thickening at the vaginal apex. Colposcopy found a pinpoint opening in this area, and a cytobrush passed through the opening confirmed adenocarcinoma. Pelvic ultrasound, computed tomography scan, and CA 125 were normal. At laparotomy, the right fallopian tube and ovary were adherent to the vaginal apex. A grade II papillary serous adenocarcinoma confined to the tube was discovered. CONCLUSION: According to a MEDLINE search, this is the third report detailing a unique presentation of fallopian tube carcinoma after hysterectomy and possibly the first detected with positive Papanicolaou cytology.

Surgically documented responses to paclitaxel and cisplatin in patients with primary peritoneal carcinoma.

Intra-abdominal carcinomatosis indistinguishable from ovarian cancer may occur after removal of the ovaries or in association with surface ovarian involvement. Because its histologic pattern and behavior approximate those of ovarian cancer, this entity, known as primary peritoneal carcinoma, has been treated in a similar fashion--cytoreductive surgery followed by systemic chemotherapy. This review was undertaken to assess the efficacy of combination chemotherapy with paclitaxel and cisplatin, the current front-line chemotherapeutic regimen for ovarian cancer, in patients with primary peritoneal carcinoma. Sixteen patients diagnosed between January 1989 and July 1994 with primary peritoneal carcinoma were treated at the Hospital of the University of Pennsylvania. The records of the three patients whose initial chemotherapeutic regimen included paclitaxel and cisplatin were reviewed. An additional case from the Robert Wood Johnson Medical Center, Camden, New Jersey, was included. Pathologic review of all cases was conducted at the time of clinical management and again as part of this study. Reassessment laparotomy was performed in all patients after the completion of chemotherapy. Complete clinical information was available on all patients. All four patients presented with intra-abdominal carcinomatosis, and large volume (> 1 cm) residual disease was present following initial cytoreduction. Following chemotherapy, second-look laparotomy documented one complete pathologic response and three partial (>50% tumor volume reduction), but marked, responses. Combination chemotherapy with paclitaxel and cisplatin produces surgically documented responses in patients with primary peritoneal carcinoma.

Primary squamous cell carcinoma of the endometrium.

All reported cases of primary squamous cell carcinoma of the endometrium and the effectiveness of the different treatment modalities in the world literature are reviewed. We present the first reported case of primary squamous cell carcinoma of the endometrium treated by radical hysterectomy, pelvic and para-aortic lymphadenectomy. The patient is without signs of disease 4 years after surgery. This is the longest follow-up of all reported cases. There are very few cases from which is to conclusively predict the best mode of therapy. The current standard of treatment is total abdominal hysterectomy and bilateral salpingo-oophorectomy with or without pelvic and para-aortic lymph node sampling, depending on the histology and depth of the myometrial invasion. Adjuvant therapy includes radiation therapy according to the extent of disease.

Recurrent squamous cell carcinoma of the cervix with pulmonary lymphangitic metastasis.

A case report and review of the world literature are presented to examine all the reported cases of cervical carcinoma manifesting as pulmonary lymphangitic carcinomatosis in order to better understand this rare condition. The clinical and pathologic features of this disease process are reviewed, as are potential treatment options. We present the first reported case of an immunocompromised patient with cervical carcinoma and pulmonary lymphangitic metastasis with a prospective diagnosis made by transbronchial biopsy. Given that this condition carries a uniformly fatal prognosis, unwanted therapy may result from a missed diagnosis. A prospective pathologic diagnosis by transbronchial biopsy may guide appropriate therapy in these patients.

Metastatic cervical cancer and pelvic inflammatory disease in an AIDS patient.

The Center for Disease Control (CDC) recently added invasive cervical cancer to its list of surveillance case-defining diseases, and also included cervical dysplasia, carcinoma in situ, and pelvic inflammatory disease (PID) in the classification system. There are several reported cases of cervical cancer in AIDS patients that behaved in an unusually aggressive fashion and responded poorly to therapy. In light of the above-reported cases, it may be expected that cervical cancer may manifest itself in unusual ways in HIV-positive women. A case of aggressive cervical cancer in an AIDS patient with PID is reported. She was admitted with PID and newly diagnosed cervical cancer with recurrent fever spikes despite adequate antibiotic coverage. An aspiration of a presumed psoas abscess revealed metastatic squamous cell carcinoma. These data suggest that not only are HIV-infected women at risk for aggressive and unusual presentations of cervical cancer, but also that coexistent pelvic infection may contribute to development and spread of the disease. Immunosuppression from the virus may increase the incidence and severity of neoplasia. Data suggest that cervical cancer in HIV-infected women is often of advanced stage and responds poorly to treatment. Unique treatment approaches may need to be developed as conventional strategies do not seem to be adequate. More research is required to determine what these strategies should be. Lastly, universal HIV screening of women with either PID or cervical cancer seems prudent.

Novel agents effective against solid tumors: the diarylsulfonylureas. Synthesis, activities, and analysis of quantitative structure-activity relationships.

A series of diarylsulfonylureas with exceptionally broad-spectrum activity against syngeneic rodent solid tumors in vivo is described. Their discovery resulted from a program dedicated to in vivo screening for novel oncolytics in solid tumor models, rather than traditional ascites leukemia models. The structures, oral efficacy, side-effect profile, and mechanism of action of these sulfonylureas appear to be distinct from previously known classes of oncolytics. An extensive series of analogues was prepared to probe structure-activity relationships (SAR), with particular focus on the substituent patterns of each aryl domain. Quantitative analysis of these substituent SARs, using the method of cluster significance analysis, showed the lipophilicity of the substituents to be the dominant determinant of activity. One compound from the series, LY186641 (104, sulofenur), has progressed to Phase I clinical trials as an antitumor drug.

PUFF: an expert system for interpretation of pulmonary function data.

The application of artificial intelligence techniques to real-world problems has produced promising research results, but seldom has a system become a useful tool in its domain of expertise. Notable exceptions are the DENDRAL (1) and MOLGEN (2) systems. This paper describes PUFF, a program that interprets lung function test data and has become a working tool in the pulmonary physiology lab of a large hospital. Elements of the problem that paved the way for its success are examined, as are significant limitations of the solution that warrant further study.

Computerized consultation system for selection of antimicrobial therapy.

Mycin, a computer-based consultation system which provides to physicians antimicrobial therapy recommendations for patients with bacterial infections, is described. The consultation program arrives at therapeutic decisions using a built-in knowledge base as well as patient data entered by the physician. The system is capable of explaining its recommendations and answering questions about its reasoning process. The system's knowledge can be updated and corrected easily by infectious disease experts. At present the system is operational within a research setting; its routine use in a clinical setting will require further evaluation of its reliability and effectiveness.