Insulin-like growth factor I promotes leiomyoma cell growth in vitro

Objective: Our purpose was to determine whether insulin-like growth factors I and II preferentially stimulate uterine leiomyoma cells versus myometrial cells in monolayer culture.Study design: Leiomyomas and normal myometrium were obtained at hysterectomy from five premenopausal women. Specimens were enzymatically digested for use in primary monolayer cell cultures. By use of serum-free media, insulin-like growth factor I or II was added in 1, 10, and 100 ng/ml concentrations to both cell types with the patient serving as her own control. Cell number, prolactin production, and proliferative index values were measured on day 15 of cell culture.Results: Significant increases in cell number were found in the leiomyoma cultures (p < 0.05) treated with 10 and 100 ng/ml insulin-like growth factors I but not with insulin-like growth factos II. Neither factor exerted a stimulatory effect on myometrial cells.Conclusion: Insulin-like growth factor sI preferentially stimulates leiomyoma cells in monolayer culture. These results suggest an autocrine-paracine role in vivo for this factor in conjuction with gonadal steroids in promoting leiomyoma growth.     

Four cycles of BEP versus an alternating regime of PVB and BEP in patients with poor-prognosis metastatic testicular non-seminoma; a randomised study of the EORTC Genitourinary Tract Cancer Cooperative Group.

We have investigated whether an alternating induction chemotherapy regimen of PVB/BEP is superior to BEP in patients with poor-prognosis testicular non-seminoma. A total of 234 eligible patients were randomised to receive an alternating schedule of PVB/BEP for a total of four cycles or four cycles of BEP. Poor prognosis was defined as any of the following: lymph node metastases larger than 5 cm, lung metastases more than four in number or larger than 2 cm, haematogenic spread outside the lungs, such as in liver and bone, human chorionic gonadotrophin > 10,000 IU l-1 or alphafetoprotein > 1000 IU l-1. The complete response (CR) rates to PVB/BEP and BEP were similar, 76% and 72% respectively (P = 0.58). In addition, there was no significant difference in relapse rate, disease-free and overall survival at an average follow-up of 6 years. The 5-year progression-free and survival rates in both treatment groups were approximately 80%. The PVB/BEP regime was more toxic with regard to bone marrow function; the frequencies of leucocytes below 1000 microliters-1, leucocytopenic fever and platelets below 25,000 microliters-1, throughout four cycles were 28% vs 5% (P < 0.001), 16% vs 5% (P = 0.006), and 10% vs 1% (P = 0.001) respectively. Neuropathy also occurred more often in the PVB/BEP arm: 47% vs 25% (P = 0.001). This study shows that an alternating regimen of PVB/BEP is not superior to BEP and that it is more myelo- and neurotoxic.     

Phase II trials of fosquidone (GR63178A) in carcinoma of the breast, head and neck, ovary and melanoma.

A total of 91 eligible patients with metastatic cancer have been treated in a series of phase II trials of the novel pentacyclic pyrroloquinone, fosquidone. Tumour types were breast (24), ovary (25), head and neck (21) and melanoma (21). All patients, except those with melanoma had received prior chemotherapy. The drug was given intravenously as a 20 min infusion, at the dose of 120 mg/m2 on days 1 to 5 of a 3 week cycle. Treatment was well tolerated; the only significant side-effects being mild headaches and generalised musculo-skeletal pains. Response was assessed after 2 cycles of therapy. Only one patient (with head and neck cancer) achieved an objective partial response, lasting 6 weeks. A total of 12 patients demonstrated stable disease for a median duration of 15 to 20 weeks. Using this schedule of administration, fosquidone has no significant antitumour activity in this group of tumours.     

The Workup for Bariatric Surgery Does Not Require a Routine Upper Gastrointestinal Series

Background: Morbid obesity is a serious disease that afflicts over five million Americans, threatening their health with such co-morbidities as diabetes, arthritis, pulmonary failure and stroke. Surgery is the only effective therapy, providing long-term control of weight, diabetes, pulmonary failure, and hypertension for as long as 14 years. Because the operation presents a major expense, this study examined whether X-ray examination of the gut could be omitted safely as a cost-saving measure. Methods: The records of 814 consecutive morbidly obese patients who underwent gastric bypass were reviewed to determine: (1) whether these individuals had undergone an upper gastro-intestinal (GI) series, and (2) if these studies influenced therapy or caused cancellation or postponement of surgery. Results: Of the 814 patients, 657 (80.7%) underwent a preoperative GI radiography. Of these examinations, 393 (59.8%) were normal, with the following abnormalities in the remaining 264: hiatal hernia, 164; esophageal reflux, 39; Schatzki's ring, 18; small bowel diverticula, four; renal stones, four; malrotation, three; gall stones, two; pyloric ulcer, one; possible pelvic mass, one; calcified leiomyoma, one; and dysphagial lusoria, one. None of these findings resulted in cancellation or a delay in surgery. Conclusions: The upper GI series can be safely omitted from the routine preoperative evaluation of patients undergoing gastric bypass. At a cost of $741.00 per examination, this change represents significant potential savings. Similar evaluations of other routine preoperative tests may well provide a better basis for the evaluation of these complex patients.     

Accommodative hysteresis under static and dynamic stimulus conditions

The influence of continuous variation in dioptric demand on the accommodative hysteresis induced at near distances was examined in 14 visually-normal young adults. Tonic accommodation was measured before and after 10 minutes of sustained focus using a constant stimulus at 5 D, 6.5 D, and 8 D, as well as a stimulus which slowly and alternately increased and decreased over the continuous range from 5 D to 8 D. For approximately half the subjects, dioptric demand had to be very high (8 D) under static conditions to produce moderate but significant hysteresis, yet little or no attenuation of the effect occurred under the dynamic condition. For other subjects who consistently showed very large tonic changes (1.4 D or more) under static conditions, the hysteresis effect generated under dynamic conditions was greatly reduced (approximately 50 per cent) in magnitude. These findings suggest that the degree to which continuous variation in dioptric demand will disrupt the adaptive process may depend on individual differences in the rate and/or maximum level of tonic accommodative change. Such a relationship could have bearing on the particular strategy recommended for individuals who tend to experience blur at distance following nearwork.     

High-dose epirubicin in chemotherapy refractory non-seminomatous germ cell cancer: a phase II study. EORTC Genito-Urinary Tract Cancer Co-operative Group. EORTC Early Clinical Trials Group.

Eighteen patients with progressive disseminated, platinum-resistant germ cell tumors were treated with epirubicin 135 mg/m2, every 3 weeks. One patient had stable disease, 17 developed progression. Myelosuppression was dose-limiting. One patient died of neutropenic septicemia. High-dose epirubicin is not active against platinum-resistant germ cell cancer.