Effect of paternal administration of an antiestrogen, tamoxifen on embryo development in rats

We have earlier reported that oral administration of tamoxifen causes a dose-dependent reduction in the fertility of adult male rats. The decrease in fertility was mainly due to an increase in pre-implantation loss without an effect on fertilizing ability. During the study, an increased incidence of post-implantation loss of conceptuses sired by tamoxifen-treated male rats was observed. A detailed study was undertaken to investigate dose-related changes in pre- and post-implantation loss and the stage(s) of development at which these losses occurred. The present study demonstrates that tamoxifen treatment produced few normal litters as well as significantly increased pre-implantation loss without affecting the rate of fertilization. Also a significant increase in the number of degenerating embryos at the 2–4-cell stage (days 1–2 of gestation), retrieved from the oviduct/uterus of females mated with tamoxifen-treated males was observed. Histology of the resorbed fetuses, in both control and treated groups, showed presence of trophoblast outgrowth indicative of early placenta formation, which normally occurs on days 8–9 of gestation. The present results suggest that pre-implantation loss occurred at the 2–4-cell stage and the post-implantation loss occurred around days 8–9 of gestation, i.e. around midgestation. The possible effects of paternal tamoxifen treatment on embryogenesis may be due to the reduction of androgens or by the blockage of the estrogen receptor by tamoxifen, thereby affecting germ cell maturation during spermatogenesis.     

Comparison of two colloidal silica-based sperm separation media with a non-silica-based medium

OBJECTIVE: To study and compare the effects of three sperm separation media, two silica-based (Percoll; Pharmacia Biotech AB, Uppsala, Sweden, and Isolate; Irvine Scientific, Santa Ana, CA) and one non-silica-based (Ixaprep; Medicult, Copenhagen, Denmark), on the recovery of progressive motile sperm, the percentage of sperm with normal morphology, various sperm motion characteristics determined by computer-aided sperm analysis, and the percentage of acrosome-reacted sperm. DESIGN: Prospective study. SETTING: A university-based assisted reproductive technology center. PATIENT(S): Male partners of couples attending our infertility clinic. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Various semen parameters. RESULT(S): Both Isolate and Ixaprep resulted in enhanced recovery of motile spermatozoa compared with Percoll. The percentage of sperm with forward progressive motility, the percentage of sperm with normal morphology, and various sperm motion characteristics were similar after the use of Percoll and Isolate and were significantly better than after the use of Ixaprep. The same percentage of acrosome-reacted spermatozoa was observed with all three media. Similar results were observed in both normal and subnormal semen samples. CONCLUSION(S): The use of Isolate and Ixaprep resulted in better recovery of motile spermatozoa. Other semen parameters were similar with the use of Isolate and Percoll, whereas the use of Ixaprep was associated with lower sperm velocities and fewer morphologically normal spermatozoa.     

Oak (Quercus incana) leaf poisoning in cattle.

Oak poisoning occurred in crossbred cattle due to eating immature tender oak (Quercus incana) leaves. Mortality was 70%. The animals exhibited anorexia, severe constipation and brisket edema. The feces were hard, pelleted and coated with blood and mucous. Significant reductions in blood hemoglobin and mean corpuscular hemoglobin, and significant elevations in serum bilirubin were observed. Serum urea nitrogen and creatinine were greatly increased. There was bilirubinuria, proteinuria, hypoproteinemia and hypocalcemia, and greatly increased activities of serum aspartate aminotransferase, lactate dehydrogenase and alkaline phosphatase. The levels of tannins and condensed tannins were 97.7 mg tannic acid equivalent and 5.8 mg catechin equivalent/g of dry leaves. There was extensive nephro- and hepatotoxicity in the affected cattle due to hydrolysable tannins and simple phenols in the oak leaves.     

Paclitaxel added to the cisplatin/etoposide regimen in extensive-stage small cell lung cancer -- the use of complete response rate as the primary endpoint in phase II trials

Obtaining a complete response (CR) is the most powerful predictor of survival in extensive-stage small cell lung cancer (SCLC). Improvements in long-term survival in extensive-stage SCLC can be made if the proportion of complete responders to induction therapy can be increased. We performed a phase II trial of the feasibility of adding paclitaxel to standard cisplatin/etoposide (EP regimen) in extensive-stage SCLC. The primary endpoint for this trial is the proportion of patients (pts) obtaining a CR rather than overall response. The null hypothesis for this trial consists of the absence of a CR rate >20%. Paclitaxel was given at doses of 135 (3 pts) or 170 mg/m(2) i.v. over 3 h on day 1. Cisplatin 60 mg/m(2) was given on day 1. On days 1-3 etoposide 80 mg/m(2) per day i.v. was given. G-CSF was used from days 5 to 14 of each cycle. Cycles were repeated q21 days. A two-stage design was used for patient accrual, based on the occurrence of complete responses. Initially, 16 patients were to be accrued. If more than three complete responses were to occur, a further 20 patients would be accrued to the study (Simon's optimal two stage design). Sixteen patients were enrolled. Two patients had a CR (13%) and nine patients had a partial response (56%) for an overall response rate of 69%. The trial was suspended due to the low CR rate. Review of the literature for paclitaxel based front-line treatment combined with EP therapy, in extensive stage SCLC, consistently shows a CR rate <20% but high overall response rate is maintained (thus most responses are partial). As virtually all long-term survivors in extensive-disease SCLC have had a CR to induction therapy and CR remains the strongest predictor of survival for this disease, this may suggest that paclitaxel added to standard EP may improve progression-free survival (and possibly median survival) but is unlikely to significantly improve long-term survival. Initial randomized phase III data confirm the absence of impact on survival for this triple-drug regimen compared to EP therapy alone. Furthermore, other regimens comparing favorably to the EP regimen have all shown consistent CR rates >20% in the phase II setting. In conclusion, consideration should be given to the use of CR rate as a phase II endpoint to determine if a particular regimen should be compared to the standard in a phase III setting for extensive-stage SCLC. A two-stage phase II design based on a minimum required completed responses for further patient accrual is recommended.     

Glycoprotein IIb/IIIa receptor antagonists: clinical pharmacology in cardiovascular diseases of aging.

The aging process is accompanied by a series of anatomical and physiological cardiovascular changes, including a generalised loss of vascular compliance, neuroendocrine alterations and endothelial dysfunction. Superimposed on this, there is an age-related increase in common cardiovascular disorders, such that the majority of deaths and much disability in older populations are caused by coronary artery disease. Most acute vascular events are mediated by thrombosis in which the formation of platelet aggregates forms an integral part. Research over recent years has led to the characterisation of the platelet glycoprotein (GP) IIb/IIIa receptor as the ultimate mechanism by which activated platelets cross-link by binding fibrinogen and other ligands. This knowledge has resulted in novel pharmacological strategies targeting this receptor which have proven to be potent inhibitors of thrombosis. The prototype drug, abciximab, is a chimeric monoclonal antibody directed against GP IIb/IIIa. Synthesis of new drugs has followed, based on the identification of the molecular sequences to which GP IIb/IIIa is attracted. This includes the emergence of oral agents which can be used for long term therapy. Clinical trials with these agents in the setting of percutaneous coronary interventions and unstable ischaemic syndromes have demonstrated a beneficial effect on thrombosis-related end-points. Trials of GP IIb/IIIa antagonists for direct percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction have also shown benefit, while their use in combination with fibrinolytic drugs is currently being evaluated. Other potential indications including neurovascular disease and primary haematological disorders are also being explored.     

Failure of High Risk Women to Produce Nipple Aspirate Fluid Does Not Exclude Detection of Cytologic Atypia in Random Periareolar Fine Needle Aspiration Specimens

INTRODUCTION: Evidence of hyperplasia with atypia found both on random periareolar fine needle aspiration (RPFNA) and in nipple aspirate fluid (NAF) fluid are associated with an increased risk for breast cancer. AIM: In this study, we report the correlation of NAF production with cytological assessment of ductal cells obtained by RPFNA. METHODS: 113 women at high risk for development of breast cancer attending the Breast Cancer Prevention Clinic at the University of Kansas Medical Center underwent a single NAF collection attempt and RPFNA. RESULTS: NAF was successfully collected in 51% of women. There was no significant difference in age, 5-year Gail risk assessment, menopausal status, hormone use, family history of breast cancer, history of prior atypical hyperplasia/LCIS or history of contralateral DCIS/invasive breast cancer between women who produced NAF and those that did not. The only significant difference between the two groups was in history of prior lactation (p = 0.018). Twenty-seven of the 113 subjects were found to have hyperplasia with atypia by RPFNA was 31% in women who produced NAF versus 16% in those who did not (p = 0.07). CONCLUSION: Although prevalence of RPFNA atypia was numerically higher in NAF producers than non-producers the difference did not reach statistical significance. Failure to produce NAF does not exclude the presence of hyperplasia with atypia by random periareolar fine needle aspiration.     

A case report of an unusual presentation of ocular rhinosporidiosis as a conjunctival cystic mass

Ocular involvement of rhinosporidiosis is seen in about 15% of cases and clinically appears as a freely mobile, granular, pink, fleshy sessile or pedunculated mass. The conjunctiva is the most common site of origin. A 25-year-old male presented with a painless mass in the lower part of the left eye for 6 months which was gradually progressive. Examination revealed a pedunculated mass of 15 mm x 15 mm arising from the lower palpebrae of the left eye retracting the lower lid. It appeared to be vascular with few white spots at the apex. Rest of the ocular examinations was within the normal limit. The presentations of ocular rhinosporidiosis vary. Though the conjunctival origin is very common, it may not have a classic pink fleshy appearance at all times. A vascular/cystic painless conjunctival mass should also be considered as a case of rhinosporidiosis in prone areas.