Motives for parenthood and response to failed in vitro fertilization: Implications for counseling

The purpose of this investigation was to identify in vitro fertilization (IVF) candidates' motives for parenthood and hence for seeking treatment. The relationship among identified motives, pretreatment emotional adjustment, and reaction to treatment failure was then examined. Women as a group placed greatest emphasis on fulfilling gender-role requirements, and those strongly endorsing such motives showed the poorest adjustment before IVF and the most negative reaction to first-cycle failure. In contrast, men in general were more likely to stress a desire for marital completion, although this motive was not predictive of emotional status before or after IVF. However, men experiencing social pressures to have children were at greater risk when treatment failed. The results indicate that greater consideration of cognitive factors may enhance understanding of emotional reactions to IVF failure and provide important insights for therapeutic intervention.     

Use of Balloon-expandable stents to treat experimental peripheral pulmonary artery and superior vena caval stenosis: Preliminary experience

Summary Current therapy of congenital or acquired stenoses of the peripheral pulmonary arteries and superior vena cava are frequently ineffective. This report describes our initial experience with the use of a balloon-expandable stainless steel stent to treat experimentally created branch pulmonary artery and superior vena cava stenosis. Fifteen adult mongrel dogs had surgically created stenoses of either a branch pulmonary artery and/or superior vena cava. A balloon-expandable stainless steel (0.076 mm), 3 cm long, intravascular stent was used in all animals. Stents were successfully placed in 13 of 15 dogs (nine with branch pulmonary stenosis and four with superior vena caval stenosis) with hemodynamic and angiographic relief of the stenoses in all. In three animals, successful stent placement was not accomplished because the distal right pulmonary artery was found to be totally obstructed in two and in one dog with combined vena cava and pulmonary stenosis the distal right pulmonary artery was so severely stenotic that the stenosis could not be crossed. Repeat catheterization performed 6 months following stent placement documented persistent gradient relief and angiographic evidence of unobstructed flow through the stent without thrombus formation and with patent side branch vessels. Our preliminary results suggests that balloon-expandable stents are a potential therapy for the treatment of branch pulmonary artery and superior vena cava stenoses.     

A Phase II Study of Continuous Infusion of Trimetrexate in Patients with Refractory Acute Leukemia

Trimetrexate, a second-generation folate antagonist, is a potent inhibitor of dihydrofolate reductase with a broader spectrum of activity and different mechanism of entry and intracellular accumulation than methotrexate. Six patients with refractory or relapsed acute leukemia were treated with a 5-day continuous infusion of trimetrexate of 8 mg/m² /day after an initial loading dose of 4 mg/m² to achieve a target plasma concentration of 0.2-0.5 μM. In 4 patients with peripheral blasts at study entry, transient decrease or disappearance of blasts was observed, although no decrease of bone marrow blasts occurred. Mucositis was dose-limiting and severe in 4 patients. Neutrophil and platelet nadirs occurred on day 5-12 postinfusion. Because of dose-limiting mucositis, this dose schedule of trimetrexate is not recommended for further studies in refractory acute leukemia. However, other dose schedules (24- to 72-hr infusions) and its use as a modulating agent with thiopurines or leucovorin in patients that are resistant to methotrexate should be explored.     

Preliminary experince with a combination of clomiphene and variable dosages of menopausal gonadotropins for enhanced follicular recruitment

A combination of clomiphene citrate and human menopausal gonadotropin was employed for enhanced follicular recruitment in an in vitro fertilization program. All patients received 50 mg of clomiphene and 1 ampule of human menopausal gonadotropin daily from cycle day 5 through cycle day 9. Follicular monitoring was begun on day 10 using a combination of ultrasound measurement of follicular size and number and determination of peripheral estradiol levels. Based on the size and number of follicles, the peirpheral levels of estradiol, and the rate of follicular growth and increase in estradiol, human menopausal gonadotropin was continued at a dosage of 1 to 3 ampules/day through the day of human chorionic gonadotropin administration. Human chorionic gonadotropin was administered on the evening of the day the largest follicle reached or exceeded 20 mm in mean diameter if the estradiol levels had been rapidly rising or reaching a plateau and had exceeded a minimal level of 300 pg/ml. Using this protocol, 30 of 33 patients underwent laparoscopy, 29 patients had successful oocyte recovery, and 23 patients underwent embryo replacement, with the establishment of six clinical pregnancies.     

Effects of latanoprost on tyrosinase activity and mitotic index of cultured melanoma lines

The intraocular pressure-lowering drug latanoprost, a phenyl-substituted analogue of prostaglandin F2 alpha (PGF2 alpha), increases iris pigmentation in a small number of patients. In theory, this could be due to increased melanogenesis or melanocyte proliferation. To distinguish these two possibilities, the present study examined the effects of latanoprost on tyrosinase activity (the rate-limiting step for melanin synthesis) and mitotic index of cultured melanoma lines. Murine cutaneous melanoma lines (S91 and B16), and human uveal (OCM1, OCM3, and OM431) and cutaneous (SK-MEL5 and M21) melanoma lines were cultured with PGE1, PGE2, PGF2 alpha, latanoprost, or the adenylate cyclase stimulating agent forskolin. After treatment, tyrosinase was assayed with respect to its dopa oxidase activity using a colorimetric assay. PGE1, PGE2, PGF2 alpha, and latanoprost greatly increased tyrosinase activity in murine melanoma lines and caused small increases in tyrosinase activity in human uveal and cutaneous melanoma lines. Similar results were obtained with the cAMP-elevating compound forskolin. Cyclic AMP content, as determined by an enzyme-linked immunoassay, was similarly increased by all treatments, with forskolin being the most potent stimulator. Since the species difference in tyrosinase activity was observed without an apparent difference in induction of cAMP, latanoprost would appear to induce tyrosinase activity through a non-cAMP-dependent pathway. Finally, latanoprost and PGF2 alpha did not enhance the mitotic index of human uveal or cutaneous melanoma lines, measured by [6-3H] thymidine uptake, although they increased the mitotic index of one murine cutaneous line. Given that latanoprost induced tyrosinase activity, but did not increase the mitotic index in any of the human melanoma lines studied, this suggests that the in vivo iris pigmentation side effect of latanoprost may not result from increased cell division, but from elevated tyrosinase activity.     

Hematopoietic growth factor (G-CSF or GM-CSF) after salvage chemotherapy in refractory or relapsed adult de novo acute leukemia

Nineteen adults with primary refractory or relapsed acute leukemia (12 ALL and 7 ANLL) were treated with an intensive salvage chemotherapy (intermediate-dose ara-C, intermediate-dose methotrexate, vindesine, cyclophosphamide, mitoxantrone and prednisolone) followed by a hematopoietic growth factor (HGF), either granulocyte colony-stimulating factor (5 μg/kg) or granulocyte-macrophage colony-stimulating factor (10 μg/kg). Both were given from the day after chemotherapy ended and until the neutrophil count rose above 1 × 10⁹/l for three consecutive days. Eleven patients (58%. 95% CI 33% to 82%) achieved complete remission, and 15 courses of salvage therapy were given to these complete responders. In a historical control group that did not receive HGF, 23 out of 38 patients (60%, 95% CI 44% to 77%) achieved complete remission, and 27 courses of therapy were delivered to complete responders. Treatment with a HGF accelerated the recovery of neutrophils to 0.5 × 10⁹/l significantly, shortening it from a mean of 28 to 22 days (p = .0002), with no effect on platelet recovery. There were no differences in the rates of documented and fatal infections, which were relatively high in both groups. In the patients with ANLL, there was no evidence that HGF accelerated leukemic regrowth. We conclude that HGF accelerates neutrophilic recovery following intensive salvage chemotherapy for acute leukemia, although no reduction in documented infections was found. Many factors, including the small patient sample, may have contributed to this latter finding.     

Aminophylline toxicity

Aminophylline therapy has undergone change in the past decade. With the changes in usage and dosage forms, the frequency of toxicity in the pediatric population, especially in adolescents, has increased dramatically. Two distinct patterns, chronic and acute, have been recognized and treatment methods for both are changing. Table 4 summarizes the emerging state-of-the-art therapy for aminophylline toxicity. Judging from the activity seen in the literature, investigation into aminophylline toxicity will continue to be a priority. We will see a greater understanding of the disease process and a refining of the therapeutic process. The ultimate goal is the elimination of mortality and the minimization of morbidity from aminophylline toxicity.     

Pregnancy following induction of ovulation with pure FSH after suppression of endogenous gonadotropins with subcutaneous Buserelin

Summary Ovarian stimulation in patients with disorders of ovulation or an inadequate luteal phase using human menopausal gonadotropins (hMG) gives a low pregnancy rate with a high incidence of overstimulation and a premature LH surge. In order to overcome these problems, a new approach has been used, namely prior suppression of endogenous gonadotropins with a gonadotropin-releasing-hormone analog (LHRH) and subsequent ovarian stimulation with hMG. We present a case of ovarian stimulation with pure FSH during suppression of endogenous gonadotropins with the LHRH analog Buserelin. A clinical pregnancy was achieved in the first treatment cycle and led us to conclude that follicular development does not depend on LH stimulation. This could be of substantial interest in IVF programs.