Primary sarcoma of the adult vagina: a clinicopathologic study

Combination chemotherapy has dramatically improved the results of treatment for embryonal rhabdomyosarcoma of the vagina in children, but little attention has been directed toward vaginal sarcomas in adults. This report of 17 cases of primary sarcoma of the adult vagina includes ten leiomyosarcomas, four mixed mesodermal tumors, one undifferentiated sarcoma, one stromal sarcoma, and one neurofibrosarcoma. The leiomyosarcomas, mixed mesodermal tumors, and the stromal sarcoma were morphologically similar to their uterine counterparts. Thirty-five percent of the patients had received pelvic irradiation for carcinoma of the cervix. Three of four patients treated by pelvic exenteration are alive and disease free after 84 to 161 months of observation. All 13 patients who received other forms of primary therapy died of recurrence. The pelvis was the first site of recurrence in all treatment failures and the only site of failure in 50%.     

De-misting condensation on intraocular lenses

BACKGROUND: Condensation occurs rapidly on intraocular lenses (IOLs), particularly silicone IOLs, after vitrectomy and fluid-air exchange in the presence of a posterior capsulotomy and severely limits the surgeon's view of the retina. This study investigated the value of heating contact lens irrigation fluid to prevent condensation on IOLs. DESIGN: An experimental in vitro study and a noncomparative interventional case series. PARTICIPANTS: Five control eyes had temperature measurements during fluid-air exchanges. Two patients with silicone IOLs and posterior capsulotomies underwent a vitrectomy involving a fluid-air exchange with heated contact lens fluid. METHODS: An in vitro model allowed monitoring of temperature and humidity changes during condensation formation on four different IOL materials. Adjusting variables to promote evaporation rather than condensation was achieved in vitro. In vivo, intraocular temperatures were measured at various stages of five vitrectomies involving a fluid-air exchange. Finally, in two in vivo cases a blood warmer was used to heat the accessory contact lens irrigation fluid during the vitrectomy and fluid-air exchange. MAIN OUTCOME MEASURES: Successful prevention of condensation on the silicone IOL during the fluid-air exchange. RESULTS: Anterior segment temperature influences the IOL temperature, such that when it is higher than the posterior segment temperature, condensation does not form and evaporation is promoted. In vivo the temperatures in the eye are hypothermic throughout the vitrectomy. At fluid-air exchange the posterior segment heats rapidly as irrigation ceases and low specific heat gas enters. Finally, in two in vivo cases with silicone IOLs, condensation was predicted then prevented by our intervention for the duration of the fluid-air exchange. CONCLUSIONS: Heating the anterior segment by conduction from warmed irrigation fluid flowing through the irrigating contact lens represents a cheap, noninvasive, and safe means to prevent condensation on IOL materials.     

Does father's unemployment put the fetus at risk?

Summary. Information concerning 15037 singleton deliveries in 1970 showed that among the 3.5% where the male head of the household was unemployed there was no significant excess of low birthweight or pre-term delivery, once social class had been taken into account. There were major differences, however, in maternal health behaviour. In order to ascertain whether the health behaviour might be a consequence of the unemployment, data were also analysed for the 658 pregnancies in women whose husbands, though employed at delivery, were subsequently unemployed. Almost identical patterns were found, implying that the association with health behaviour was not a time-related consequence of unemployment.     

Comparison of isotonic and hypertonic fluids in resuscitation from hypovolemic shock

Hypertonic electrolyte solutions provide effective fluids for resuscitation of burn patients and concurrent replacement of hemorrhage. Infusion of mannitol has also been advocated as a means of increasing cardiac output in acutely ill patients. Pigs which were bled to one-third of their blood volume were used in this random study of resuscitation with Ringer's lactate solution (RL), hypertonic saline solution (HSL) and RL with mannitol added (HMR) to give the same osmolality as HSL. Smaller volumes of the hyposmolar solution than of RL restored blood pressure and cardiac output. RL and HSL restored and maintained cardiac output more effectively than HMR. At 24 hours, HSL maintained blood pressure most effectively.     

PCP in the blood plasma: current exposure of the population in Germany, based on data obtained in 1998

The fungicidal substance pentachlorophenol (PCP) had been used commonly for wood protection and leather impregnation in Germany until 1989, when this substance was prohibited by law. Hence, the body burden in the general population in Germany has been steadily declining. The reference values (95th percentiles) in blood plasma decreased from 20 micrograms PCP/l in 1991 to 12 micrograms/l in 1996. In 1998 the current exposure in a large residential population was investigated. 623 persons with an average age of 34.6 years (0-62 years) were investigated. For all of them there was neither evidence of occupational contact with PCP nor of the presence of PCP in the residential indoor environment. The mean PCP concentration in the plasma samples was 2.4 +/- 3.9 micrograms/l, the median 1.7 micrograms/l, and the 95th percentile 6.1 micrograms/l, the maximum value was 59.3 micrograms/l. In children and adolescents higher median and 95th percentiles were obtained than in adults (median 2.5 vs. 1.5 micrograms/l and 95th percentile 7.7 vs. 5.9 micrograms/l). All values above 20 micrograms/l were checked again individually: relationships with the level of PCP in household dust could not be detected. In one family leather clothing containing PCP, however, was found to be the cause of unusually high PCP values in the blood. Our investigations confirm a trend observed in recent years: exposure to PCP in the population in Germany decreases steadily and leads to an actualized reference value of 6.1 micrograms PCP/l plasma. In individual cases, however, greatly increased PCP levels in blood can still occur today, for example due to leather clothing treated with PCP.     

Comparison of the Goldmann-Weekers Dark Adaptometer™ and LKC Technologies Scotopic Sensitivity Tester-1™

The standard for dark adaptation has long been the Goldmann-Weekers Dark Adaptometer (Haag-Streit). More recently, portable, relatively inexpensive LED-based dark adaptometers have become commercially available. These devices have potential use in areas with limited resources to screen for night-blindness, commonly caused worldwide by vitamin A deficiency. In order to determine the sensitivity to detecting changes in night vision, this study compared one such device, LKC Technologies Scotopic Sensitivity Tester-1 (SST- 1) to the Goldmann-Weekers in patients with hereditary retinal degeneration and loss of rod function. Dark-adapted final thresholds and rod full-field ERG responses were obtained from 87 patients and 24 normal subjects. Linear regression analysis, discrepancy analysis, and receiver operator characteristic curves for both devices show that the SST-1 quantifies psychophysical rod function nearly as well as the Goldmann-Weekers, within some limitations. We conclude, therefore, that the SST-1 is a viable alternative to the Goldmann-Weekers for the screening of night-blinding retinal disorders.     

Sexual, reproductive, and other risk factors for adenocarcinoma of the cervix: results from a population-based case-control study (California, United States)

The incidence of adenocarcinoma of the cervix increased steadily in young women in the United States between the early 1970s and the mid-1980s. Despite this increase, little is known about the etiology of this cancer, although a role for risk factors for both squamous cell carcinoma of the cervix and endometrial adenocarcinoma has been suggested. Incident cases of adenocarcinoma of the cervix diagnosed in women born after 1935 (ages 42 to 56 at diagnosis) were identified from the Los Angeles (California) County Cancer Surveillance Program (LACCSP). Data from personal interviews with 195 cases and 386 controls (matched on age, race, and neighborhood) were analyzed. Compared with women in the highest categories of education and income, women in the lowest categories had a 2.5 and 3.1-fold elevated risk of adenocarcinoma of the cervix. Number of sexual partners, especially before age 20, was strongly predictive of risk (odds ratio = 5.6, 95 percent confidence interval = 1.4–22.0 for 10 or more compared with no partners before age 20). Smoking was not associated significantly with risk. Weight gain and long-term use of oral contraceptives increased risk, while long-term diaphragm use was protective. This study suggests that both sexual and hormonal factors are important etiologic factors for adenocarcinoma of the cervix.Drs Ursin, Pike, Preston-Martin, and Peters are with the Department of Preventive Medicine, University of Southern California School of Medicine, Los Angeles, CA, USA. Dr D'Ablaing, now deceased, was with the Department of Pathology at the University of Southern California School of Medicine. Address correspondence to Dr Ursin, Department of Preventive Medicine, University of Southern California Norris Comprehensive Cancer Center, 1441 Eastlake Ave., MS#44, P.O. Box 33800, Los Angeles, CA 90033-0800, USA. This study was supported by grants P01 CA1754 and CA 44401-05 from the US National Cancer Institute, and by the California Department of Health Services, through the California Public Health Foundation, as part of its statewide cancer reporting program, mandated by Health and Safety Code Sections 210 and 211.3. The ideas and opinions expressed herein are those of the authors, and no endorsement by the State of California Department of Health Services or the California Public Health Foundation is intended or should be inferred.     

A phase I/II study of high-dose cyclophosphamide,cisplatin, and thioTEPA followed by autologous bone marrow and granulocyte colony-stimulating factor-primed peripheral-blood progenitor cells in patients with advanced malignancies

 The purpose of the present study was to determine the maximally tolerated dose of thioTEPA given with fixed high-dose cyclophosphamide (CPA) and cisplatin (cDDP) followed by autologous bone marrow (ABM) with or without granulocyte colonystimulating factor (G-CSF)-primed peripheral-blood progenitor cells (PBPCs) in patients with advanced malignancies. Patients were required to have histologically documented malignancies and adequate renal, hepatic, pulmonary, and cardiac function. CPA was given at 1,875 mg/m² per day as a 1-h i.v. infusion for 3 consecutive days, and cDDP was given at 55 mg/m² per day as a 24-h continuous i.v. infusion over 3 days concurrently with CPA. ThioTEPA was given once as a 1-h i.v. infusion (300–900 mg/m²) either following (the first 13 patients) or prior to CPA and cDDP. In all, 31 patients received PBPCs. A total of 46 patients were treated. There were 6 deaths among the 15 patients who did not receive PBPCs (13 received thioTEPA following CPA and cDDP). Among the other 31 patients who received PBPCs (all of whom also received thioTEPA prior to CPA and cDDP), there were 4 deaths, all involving patients with refractory ovarian carcinoma. The main toxicities were mucositis, esophagitis, hepatotoxicity, and nephrotoxicity. The median time required to achieve an absolute neutrophil count of 500 μl was 10 days (range, 9–12 days) for those who received PBPCs and 15 days (range, 15–34 days) for those who did not receive PBPCs. Altogether, 47% of the major organ toxicities (grades 3 and 4 renal, hepatic, and cardiac toxicities) occurred among the 15 patients who did not receive PBPCs, although these patients received thioTEPA at the lowest 2 dose levels. There were 3 complete responses and 22 partial responses among 35 evaluable patients (overall response rate, 71%), with the median duration of response being 3.5 months (range, 2–17 months). The maximally tolerated dose of thioTEPA was 600 mg/m² given as a 1-h i.v. infusion on the day prior to CPA and cDDP administration. The combination of high-dose CPA, cDDP, and thioTEPA is a well-tolerated regimen when thioTEPA is given prior to CPA and cDDP and when the combination also includes PBPCs in addition to ABM. This regimen is active in a variety of malignancies. Received: 15 February 1995/Accepted: 22 May 1995     

Antitumor activity of prolonged as compared with bolus administration of 2′,2′-difluorodeoxycytidine in vivo against murine colon tumors

2′,2′-Difluorodeoxycytidine (gemcitabine) is a cytidine analogue with established antitumor activity against several experimental tumor types and against human ovarian and non-small-cell lung cancer. Both preclinical studies and most clinical trials involving patients with solid tumors have focused on short-term administration schedules; however, mechanistic studies indicate that a continuous-infusion schedule may be more effective. We determined the maximal tolerated dose (MTD) of gemcitabine in mice using various schedules. At these MTDs we observed considerably better antitumor activity of gemcitabine in two of three murine colon carcinoma lines using a prolonged administration as compared with a standard bolus protocol (i.p. 120?mg/kg q3d×4). On the latter schedule, Colon 26–10 grown in BALB/c mice was the most sensitive tumor line, showing a growth-delay factor (GDF, number of doubling times gained by the treatment) of 6.7, whereas Colon 38 (grown in C57/B16 mice) was the least sensitive tumor, displaying a GDF of 0.9. Prolonged treatment (q3d×6) of Colon 26–10 at a lower dose (100?mg/kg) enhanced the antitumor activity (GDF 9.6) while producing similar toxicity. A similar weight loss was found following the continuous infusion (c.i.) of gemcitabine using Alzet osmotic pumps s.c. for 3 or 7 days (2?mg/kg), but the GDF increased to 2.4 in Colon 38 (C57/B16) as compared with that provided by the bolus injections. Continuous infusion of gemcitabine at 15?mg/kg per 24?h q7d×2 i.v. via the tail vein was more effective than bolus injection against Colon 26–10, with the GDF being >17.7 and 73% of the tumors regressing completely. However, against Colon 38 tumors this schedule was not effective (GDF 0.4), even with a 25% higher dose. The plasma pharmacokinetics of gemcitabine was determined after one bolus dose (120?mg/kg). The peak concentration of gemcitabine was 225?μM and that of the deaminated catabolite 2′,2′-difluorodeoxyuridine (dFdU) was 79?μM. The elimination of gemcitabine was much faster than that of dFdU, with the t _1/2ß values being 15?min and 8?h, respectively. For the c.i. schedules, plasma concentrations were below the detection limit of the assay (<0.5?μM). Our results suggest that prolonged infusion of gemcitabine can give a better antitumor activity than bolus injections and shows promise of being active in clinical trials.     

Clinical picture and course of children with CHARGE association

Four children are described who presented malformations according to CHARGE-Association. The primary abnormalities were choanal atresia and/or Coloboma. All four cases exhibited esophageal malformations: atresia and/or fistulas. At autopsy, three children showed arhinencephaly which is rarely observed in patients with CHARGE-Association. Patients with the main features of CHARGE-Association have a very poor prognosis depending on the severity of the malformations.