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Biomedical subjects

I R Horowitz

Publications and source records attributed to I R Horowitz.

At least 19 recordsLinked to original sources

Embryonal rhabdomyosarcoma of the uterus in a postmenopausal woman. Case report and review of the literature.

BACKGROUND: Embryonal rhabdomyosarcoma is a rare sarcoma which characteristically occurs in non genitourinary sites in children. CASE: We present a case of uterine embryonal rhabdomyosarcoma in a postmenopausal patient who presented with increasing abdominal girth, early satiety, weight loss, and pelvic pain. CONCLUSION: Embryonal rhabdomyosarcoma does not commonly originate from the uterine corpus, and it is rarely seen in postmenopausal patients. A review of the literature confirms the unique nature of this case.

Aged↗

Angiogenic role for glycodelin in tumorigenesis.

Angiogenesis plays an important role in neovascularization in tumors. Glycodelin, a hormone-responsive protein, has been detected in tumors of reproductive organs and is found in high levels in the plasma of subjects with gynecological malignancies. Glycodelin is also found in the endothelial cells of the umbilical cord and in the blood vessels of tumors. In this study, we tested whether glycodelin-rich amniotic fluid and a synthetic peptide derived from the sequence of glycodelin peptide (Gp) might promote angiogenic response by examining the migration and tube formation in human umbilical cord vein endothelial cells (HUVECs). Increased migration and tube formation of HUVECs were found in the presence of amniotic fluid and Gp, and this increase was blocked by antibody to Gp and by an anti-vascular endothelial growth factor (VEGF) antibody, suggesting that the angiogenic effects of glycodelin might be mediated by VEGF. The results also showed that Gp significantly increased the release of VEGF protein and mRNA expression in HUVECs, RL-95 (human endometrial carcinoma cells), OVCAR-3 (human ovarian adenocarcinoma cells), EM42 (human endometrial epithelial cells), THP-1 (human monocyte), and MCF-7 and MDA-MB-231 (human breast adenocarcinoma cells) cell lines. VEGF receptor Fit-1 mRNA expression in HUVECs was also increased in the presence of Gp. These findings, together with the suggestion from the literature that glycodelin may have immunosuppressive properties, suggest that glycodelin might play an important role in neovascularization during embryogenesis and tumor development.

Amino Acid Sequence↗

Cervical carcinoma: contemporary management.

Cervical carcinoma is prevented easily with proper screening. Unfortunately, many women in industrialized countries continue to have poor access to adequate medical care. In many third-world countries, cervical cancer is one of the top malignancies diagnosed. Screening should be provided for all women to prevent or diagnose cervical cancer at an early, treatable stage.

Antineoplastic Agents↗

Phase I study of paclitaxel, carboplatin, and increasing days of prolonged oral etoposide in ovarian, peritoneal, and tubal carcinoma: a gynecologic oncology group study.

PURPOSE: Given the activity of prolonged oral etoposide in platinum and paclitaxel-resistant ovarian carcinoma, a phase I trial was conducted that combined increasing days of oral etoposide therapy with paclitaxel and carboplatin in chemotherapy-naive patients with ovarian peritoneal and tubal carcinoma to establish a maximum-tolerated dose (MTD) of this combination. PATIENTS AND METHODS: Paclitaxel at 175 mg/m(2) given over 3 hours and carboplatin at an area under the curve of 5 were administered on day 1 followed by oral etoposide 50 mg/m(2)/d beginning on day 2. The number of days of etoposide therapy was escalated on the basis of toxicity. Toxicity end points included neutropenic sepsis, grade 4 thrombocytopenia, or grade 3 neutropenia or thrombocytopenia during etoposide administration. Cycles were repeated every 21 days for a maximum of six courses. Due to hematologic toxicity, the duration of the paclitaxel infusion was decreased to 1 hour for a second stage of accrual. RESULTS: Of 52 patients studied, 29 were in the first stage of accrual. Dose-limiting toxicity occurred with 8 days of oral etoposide, making the MTD six days of therapy. Twenty-three patients were entered into the second stage of accrual. Dose-limiting toxicity occurred at 12 days of oral etoposide, making the MTD 10 days of therapy. Three patients developed acute myeloid leukemia 16, 27, and 35 months after receiving a cumulative dose of 200 mg/m(2), 1,200 mg/m(2), and 2,400 mg/m(2), respectively. CONCLUSION: One-hour paclitaxel, carboplatin, and oral etoposide at 50 mg/m(2)/d for 10 days is tolerable without supportive therapy. The leukemogenic potential is cause for concern and precludes its use in chemotherapy-naive ovarian carcinoma.

Adenocarcinoma↗

Atypical presentation of microscopically advanced ovarian carcinoma.

Epithelial ovarian cancer (EOC) continues to be an academically challenging and clinically problematic disease. Even with recent advances, the overall 5-year survival is still 31% to 42% in various studies. Deaths from EOC outnumber those due to cervical, vulvar, and endometrial carcinomas combined. Screening for EOC has shown limited success in early detection. The Pap smear is not a dependable tool in EOC screening, though at times it can be the first evidence of ovarian disease. We report a case of EOC that was diagnosed during evaluation of an abnormal Pap smear. On completion of evaluation, stage IIIA endometrioid-type adenocarcinoma of the ovary was diagnosed. Occult EOC should be considered in patients with abnormal findings on cervical cytology after cervical and uterine carcinomas are ruled out.

Adenocarcinoma↗

Serum levels of macrophage colony-stimulating factor-1 in cervical human papillomavirus infection and intraepithelial neoplasia.

OBJECTIVE: Our goal was determine the correlation between serum colony stimulating factor-1 levels, cervical human papillomavirus infection, and dysplasia. STUDY DESIGN: Serum samples were obtained from control subjects from the United States and from a group of Panamanian women. Members of the latter group fell into 3 categories: those who serve as Panamanian control subjects and who test negative for human papillomavirus (n = 10); those who are high risk by history and test positive for human papillomavirus types 16/18 and 30s (n = 10); and those with the same high-risk history with biopsy-proven cervical intraepithelial neoplasia (n = 8). Serum colony-stimulating factor-1 levels were determined using enzyme-linked immunosorbent assay. Data were analyzed with the Student-Newman-Keuls and t tests. RESULTS: Mean serum colony-stimulating factor-1 levels of patients with a positive test result for human papillomavirus (1166 +/- 949 pg/mL) and cervical intraepithelial neoplasia (1295 +/- 314 pg/mL) were higher than those of control subjects from the United States (584 +/- 237 pg/mL) and those of Panamanian control subjects (520 +/- 229 pg/mL). Statistical analysis revealed the concentration of colony-stimulating factor in patients with positive test results for human papillomavirus or cervical intraepithelial neoplasia were significantly higher than in control groups. In addition, combining patients with human papillomavirus with those who have cervical intraepithelial neoplasia results in a group that has significantly higher colony-stimulating factor levels compared with control subjects. CONCLUSIONS: Both high-grade cervical dysplasia and high-risk human papillomavirus infection are associated with higher mean serum colony-stimulating factor levels, suggesting a possible role for colony-stimulating factor-1 in cervical neoplasia. Further studies are needed to understand the mechanism of colony- stimulating factor activation in human papillomavirus infection. This may assist in designing therapeutic approaches for the management of this disease.

Adult↗

Association of human papillomavirus with HIV and CD4 cell count in women with high or low numbers of sex partners.

OBJECTIVE: To explore whether HIV serostatus (HIV-1, HIV-2, and dual (HIV-D) reactivity) and CD4 cell count affect human papillomavirus (HPV) in two groups of women from Côte d'Ivoire. METHODS: We conducted a cross sectional study of two groups of women. One group had low numbers of lifetime sex partners (maternal women, n = 258) and were enrolled based on HIV serostatus. The other group had high numbers of sex partners (female sex workers, n = 278) and all consenting self identified sex workers were admitted to this study. We collected epidemiological and clinical data, and cervicovaginal lavage for HPV testing. RESULTS: The groups had different distributions of HIV seroreactivity, but the rates of HPV DNA detection were similar. Most of the HPV DNAs detected in both groups were high risk types. A strong association of high risk HPV DNA and HIV-1 seropositivity was found in both maternal women (adjusted odds ratio (OR) 7.5 (95% CI 3.2-17.4)) and in sex workers (OR 5.0 (2.1-12.0)). The maternal group also showed an association of high risk HPV DNA detection with HIV-2 (OR 3.7 (1.6-8.5)) and HIV-D (OR 12.7 (4.3-37.5)) that was not observed in the sex workers. In addition, the association of high risk HPV DNA with HIV-1 in the maternal group was independent of low CD4 cell count, while in the sex workers the association depended on CD4 cell counts < or = 500 x 10(6)/l. CONCLUSIONS: We found that an association between HPV and HIV varied depending on the sexual behaviour and CD4 cell count of the population examined.

AIDS Serodiagnosis↗

HIV and human papillomavirus as independent risk factors for cervical neoplasia in women with high or low numbers of sex partners.

OBJECTIVE: To explore whether HIV types 1 and 2 and CD4 cell count affect cervical neoplasia independent of human papillomavirus (HPV) in women with high or low numbers of sexual partners residing in Abidjan, Côte d'Ivoire. METHODS: The study population and methods are described in the companion paper. Additional methods include a Papanicolaou smear for cytological diagnosis and statistical analysis. RESULTS: In maternal women, both HIV-1 and high risk HPV were significant independent risk factors for squamous intraepithelial lesions (SIL) (adjusted odds ratio (OR) 11.0 (95% CI 1.1-112) and 5.4 (1.5-18.8), respectively). Only high levels of HPV DNA in the lavage were associated with SIL (OR 13.2 (3.6-47.8)) in the maternal group. In female sex workers, high risk HPV was significantly associated with SIL (OR 23.7 (4.4-126)); HIV seropositivity was not. Any positive level (high or low amounts) of HPV DNA was significantly associated with SIL in sex workers (ORs 15.9 (3.3-76) and 12.7 (3.6-44), respectively). There was no association of SIL with CD4 cell counts < or = 500 x 10(6)/l in HIV seropositive women from either group. CONCLUSION: HPV or HIV-1 infection independently affect cervical neoplasia in women with low numbers of sex partners.

Adolescent↗

Bilateral tubo-ovarian abscesses four years after total abdominal hysterectomy.

BACKGROUND: Pelvic inflammatory disease (PID) is a common gynecologic disorder. One known complication of PID is tubo-ovarian abscess (TOA) formation. The predominant theory on TOA formation postulates that an ascending infection from the cervix through the uterus to the fallopian tubes and ovaries results in abscess formation. Other theories include seeding via a hematogenous infection, diverticular disease, and appendicitis. CASE: A 39-year-old female patient with abdominal pain was referred to our institution and was found to have a pelvic mass. After a thorough evaluation, surgical exploration revealed the presence of TOA. No evidence of gastrointestinal disease was present. The patient's history was significant for an uncomplicated total abdominal hysterectomy for benign disease of the uterus four years prior. Abscess cultures grew Streptococcus intermedius. CONCLUSION: This case reports the rare occurrence of TOA in a patient who had undergone an abdominal hysterectomy four years prior to presentation. If the patient reports a surgical history of prior hysterectomy, TOA is often stricken from consideration. Although unlikely, adnexal abscess formation should be considered in the differential diagnosis of a patient with abdominal pain and a pelvic mass, even with a remote history of hysterectomy.

Abscess↗

Human papillomavirus and disease status following therapy for cervical cancer.

We enrolled 85 patients with invasive cervical cancer and collected cervicovaginal lavage samples at each clinical visit for diagnosis, staging, treatment, and follow-up. Lavage samples were tested by L1 consensus polymerase chain reaction for human papillomavirus (HPV). Results were compared with HPV demonstrated in tumor tissue and the clinical status at time of sample collection. Sensitivity and specificity of the lavage for detection of tumor HPV, determined on the basis of results of tests on lavage samples collected prior to therapy, were found to be 56% and 76.9%, respectively. The proportion of lavage samples detecting tumor HPV decreased significantly with treatment, from 0.54 at diagnosis to 0.03 at complete response (P < .001). Local treatment failure was associated with increased detection of tumor HPV; however, no samples were positive prior to clinically detected treatment failure. These results suggest that cervicovaginal lavage is not an effective sampling method for epidemiological analysis of HPV in cervical tumors.

Adult↗

Ninety-six-hour infusional paclitaxel as salvage therapy of ovarian cancer patients previously failing treatment with 3-hour or 24-hour paclitaxel infusion regimens.

PURPOSE: To test the hypothesis that prolonged infusion of paclitaxel (96 hours) might overcome resistance to shorter infusion schedules (3 or 24 hours) in ovarian cancer. PATIENTS AND METHODS: A total of 30 patients with advanced ovarian cancer (24 patients), primary carcinoma of the peritoneum (four patients), or fallopian tube cancer (two patients) who previously had received paclitaxel administered on either a 3-hour or 24-hour schedule were treated with the agent delivered as a 96-hour infusion (30 to 35 mg/m2/d x 4 days) on an every 3-week program. RESULTS: Although the regimen generally was well tolerated, no objective responses were observed. CONCLUSION: In patients with ovarian cancer who have shown resistance to shorter paclitaxel infusion schedules, ninety-six hour infusional paclitaxel is an inactive treatment strategy. This makes it less likely that protracted infusion of paclitaxel will improve outcome when used as part of primary therapy of ovarian cancer. An ongoing randomized study will answer that question.

Adult↗

Clinical determinants of survival from stage Ib cervical cancer in an inner-city hospital.

This study reviewed a high-risk population of inner-city women with FIGO (International Federation of Gynecologists and Obstetricians) stage Ib cervical cancer diagnosed and treated at a single institution between 1986 and 1993. The patient age at diagnosis averaged 49 years, and most of the patients were black (83%). Squamous carcinomas predominated (75%). Radiotherapy was the most frequent treatment modality (49%), followed by surgery (38%) and combined radiation/surgery (13%). The Kaplan-Meier estimated 4-year survival for all patients completing treatment was 81%. Increased survival was significantly associated with therapy. The Kaplan-Meier estimated survival at 26 months (the time of the last death in radiotherapy patients) was 66% for radiotherapy patients and 100% for those treated with surgery. Radiotherapy patients differed from surgery patients in age, tumor size, and pelvic lymph node status, indicating that treatment selection bias could explain the observed difference in survival. Age, race, histology, and cervical lesion size were not significantly associated with survival.

Adenocarcinoma↗

Uterine arteriovenous malformation necessitating hysterectomy with bilateral salpingo-oophorectomy in a young pregnant patient.

This case report describes a 31-year-old woman at 8 weeks' gestation with large arteriovenous malformation of the uterus involving bilateral uterine and ovarian arteries. She had a history of multiple pregnancy losses, as well as spontaneous copious vaginal hemorrhage. The patient underwent an embolization procedure followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy. The uterus was very small (30 g) despite its gravid status, and the overall microscopic findings indicated Müllerian system hypoplasia in addition to vascular malformation.

Adult↗

Acute hyperglycemia following intraperitoneal irrigation with 10% dextrose in a patient with pseudomyxoma peritonei.

Pseudomyxoma peritonei is a condition characterized by the production of large amounts of mucopolysaccharide by a neoplastic epithelium. Although surgical debulking and removal of the mucinous ascites may be attempted, complete removal of the material is often impossible. Intraperitoneal lavage with 10% dextrose in water (D10W) has been advocated to prevent reaccumulation of the mucus and complications such as bowel obstruction requiring repeat laparotomy. We describe a patient undergoing operation for a large abdominopelvic mass. At laparotomy, a mucinous cystadenocarcinoma of the ovary was found with a great deal of tenacious, mucinous ascites and peritoneal implants. In an effort to more efficiently remove the mucus and prevent subsequent reaccumulation, intraperitoneal irrigation with 10% dextrose in water (D10W) was performed. The patient, who gave no history of prior glucose intolerance, was soon thereafter found to be profoundly hyperglycemic (serum glucose >500 mg/dl). She was treated with insulin and recovered without evident sequelae. Practitioners should be aware of this potentially dangerous complication associated with intraperitoneal dextrose instillation.

Acute Disease↗

Phase I trial and pharmacologic trial of sequences of paclitaxel and topotecan in previously treated ovarian epithelial malignancies: a Gynecologic Oncology Group study.

PURPOSE: A phase I and pharmacologic study to evaluate the feasibility of administering paclitaxel (PTX) in combination with topotecan (TPT) without and with granulocyte colony-stimulating factor (G-CSF) in women with recurrent or refractory ovarian cancer. PATIENTS AND METHODS: TPT was administered as a 30-minute infusion daily for 5 days and PTX was given as a 24-hour infusion (PTX-24) either before TPT on day 1 or after TPT on day 5. Each patient received both schedules on an alternating basis every 3 weeks. Sequential dose escalation of TPT or PTX-24 without and with G-CSF resulted in five dosage permutations of TPT/PTX (mg/ m2): 0.75/135 without G-CSF and 0.75/135, 1.25/135, 1.50/135, and 1.25/170 with G-CSF. RESULTS: Twenty-two patients received 109 courses of therapy. Dose-limiting myelosuppression consistently occurred at the first TPT/PTX-24 dose level (0.75/135 mg/m2) in the absence of G-CSF support. Although the addition of G-CSF resulted in reduced rates of complicated neutropenia, the incidences of dose-limiting neutropenia and thrombocytopenia were unacceptably high after the doses of either TPT or PTX-24 were increased. Paired analysis showed similar hematologic toxicities between the two sequences of drug administration. The pharmacologic behavior of both TPT and PTX-24 was not altered by drug sequencing. Major antitumor responses occurred in 40% of patients with measurable and assessable disease, including 45% and 9% of patients with potentially cisplatin-sensitive and -resistant tumors, respectively. CONCLUSION: The recommended doses of TPT on a daily times-five schedule combined with PTX-24 in these patients were 0.75 mg/m2/d and 135 mg/m2, respectively, with G-CSF support. Although this dose of PTX has significant single-agent activity in ovarian cancer, the dose of TPT is much lower than the TPT dose at which single-agent activity has been observed. Due to the inability to administer near relevant single-agent doses of both drugs in combination, as well as the requirement for G-CSF support, further evaluations of this regimen in women with refractory or recurrent ovarian cancer are necessary before it can be recommended for previously treated patients in this setting.

Adult↗

Basal cell carcinoma of the vulva. A report of four cases.

BACKGROUND: Basal cell carcinoma is the most common malignant tumor of the skin, with approximately 400,000 new cases yearly in the United States. Basal cell carcinomas account for 2-3% of all vulvar malignancies. CASES: Four patients presented in the eighth and ninth decades of life (70, 78, 87 and 89 years). Seventy-five percent of patients had a unifocal lesion. Cases 3 or 4 presented with recurrent lesions at 5 and 10 years, respectively. All patients were treated with wide local excision. Surgical margins were free of disease. None of the patients had lymph nodes suspicious for malignancy. CONCLUSION: Basal cell carcinoma can present as a unifocal or multifocal lesion. The lesions are usually located on the labia majora. Patients are frequently diagnosed with basal cell carcinoma of the vulva in the eighth and ninth decades of life. Treatment consists of wide local excision. Although 50% of these cases recurred, the lesions were reexcised, with wide local resection. No metastatic lesions were identified in any of the patients.

Aged↗

Cervical cancer survival in a high risk urban population.

BACKGROUND: Cervical cancer remains an important public health problem, particularly for the urban minority population. To the authors' knowledge, determinants of cervical cancer survival have not been studied in this high risk population. METHODS: This study included all 158 women diagnosed and treated for invasive cervical cancer from January 1, 1986, through December 31, 1992, at the Grady Memorial Hospital and Clinics (Atlanta, GA). Medical records were abstracted to determine age at diagnosis, race, International Federation of Gynecology and Obstetrics (FIGO) clinical stage, treatment, and survival. Pathologic material was reviewed to confirm the diagnosis. RESULTS: Most patients (80%) were African American, and the stage distribution was similar for African American and white patients. Sixty-six (42%) had FIGO Stage I disease; 50%, Stage II or III; and 8%, Stage IV. Four-year actuarial survival differed significantly according to clinical stage (Ia = 94%, Ib = 79%, II = 39%, III = 26%, IV = 0%). Overall survival was lower for patients with glandular carcinomas than for those with squamous cell carcinomas (26% vs. 55%, P = 0.09). This difference was almost entirely due to increased mortality in patients with Stage Ib adenocarcinomas (53% vs. 88% for squamous cell carcinoma, Stage Ib, P = 0.03). CONCLUSIONS: The major prognostic markers for cervical cancer survival in this high risk patient population were clinical stage and histology, factors identical to those identified for other populations.

Black or African American↗