A randomized placebo-controlled study of the effect of transdermal vs. oral estradiol with or without gestodene on homocysteine levels.

OBJECTIVE: To assess the effect of transdermal vs. oral administration of E2 on plasma homocysteine levels and to evaluate the impact of adding a progestogen to these regimens. DESIGN: Prospective, double-blind, double-dummy, placebo-controlled study. SETTING: Outpatient clinics in two university hospitals and two teaching hospitals in The Netherlands. PATIENT(S): One hundred fifty-two healthy hysterectomized postmenopausal women. INTERVENTION(S): Thirteen 28-day treatment cycles with placebo (n = 49); transdermal 17beta-E2, 50 microg (n = 33), oral E2, 1 mg (n = 37), or oral E2, 1 mg, plus gestodene, 25 microg (n = 33), followed by four cycles of placebo in each group. MAIN OUTCOME MEASURE(S): Fasting plasma total homocysteine concentrations at baseline and cycle 4, 13, and 17. RESULT(S): Mean (+/-SD) homocysteine concentrations in the oral E2 group decreased from baseline to cycle 4 (9.0 +/- 2.5 micromol/L vs. 8.2 +/- 2.0 micromol/L; mean change, -7.6%). Homocystine values in the oral E2 plus gestodene group did not change substantially from baseline to cycle 4 (8.9 +/- 1.6 micromol/L vs. 8.6 +/- 2.0 micromol/L; mean change, -4.4%). No significant changes were observed in the transdermal E2 group. After four washout cycles, the homocysteine concentration had returned to baseline values in all groups. CONCLUSION(S): Oral E2 therapy reduced the homocysteine concentration more than did therapy with transdermal E2 or oral E2 plus gestodene. This finding may indicate a role of liver metabolism and suggests that gestodene has a negative effect on these changes.

Preoperative selection of patients with low-stage endometrial cancer at high risk of pelvic lymph node metastases.

The goal of this study was to determine diagnostic accuracy of preoperative transvaginal sonography (TVS) to assess myometrial infiltration in patients with endometrial cancer and to determine the possibility of preoperatively selecting low-stage endometrial cancer patients at high risk of lymph node metastases. The depth of myometrial infiltration of endometrial cancer was assessed using TVS before or after curettage. Infiltration was classified as superficial if less than half of the myometrium was involved, otherwise it was classified as deep infiltration. Results were compared with the histology results of the definitive specimens. Patients were classified as high risk when they satisfied two of the following three criteria: 60 years of age or older; deep myometrial infiltration; and poorly differentiated or undifferentiated tumor. A total of 93 patients from 11 clinics were analyzed. The mean age was 66.1 years (SD +/- 11.4). The sonography and histology findings were in agreement in 69 of 93 patients. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), of "deep infiltration" by preoperative TVS were 79% (95% CI 0.65-0.93), 72% (95% CI 0.61-0.83), 61% (95% CI 0.46-0.75), and 86% (95% CI 0.76-0.96), respectively. Combining tumor grade and myometrial infiltration in the hysterectomy specimen and age, 30 of 81 patients were classified as high-risk patients. Sensitivity and PPV, specificity, and NPV for preoperative diagnosis of high risk were 80% (95% CI 0.65-0.94) and 88% (95% CI 0.79-0.97), respectively. Preoperative assessment of myometrial tumor infiltration using just TVS is only moderately reliable in endometrial cancer patients. If the results of TVS, however, are combined with the patient's age and the degree of tumor differentiation in curettings, it is possible to preoperatively select endometrial cancer patients with a high risk of pelvic lymph node metastases with sufficient reliability.

Single-dose i.v. granisetron in the prevention of postoperative nausea and vomiting.

In this randomized, double-blind, parallel group, placebo-controlled, dose-ranging study, we have compared three doses (0.1 mg, 1.0 mg and 3.0 mg) of the 5-HT3 receptor antagonist, granisetron (Kytril), as prophylactic therapy for the prevention of postoperative nausea and vomiting. The aims were to determine the optimal dose of granisetron and to evaluate its safety profile. We studied 527 adult patients, undergoing elective open abdominal surgery or vaginal hysterectomy during general anaesthesia. Antiemetic prophylaxis with a single dose of granisetron 1.0 mg or 3.0 mg resulted in a significant reduction (P < 0.001 compared with placebo) in the numbers of patients experiencing postoperative vomiting, or nausea, or who achieved total control during the postoperative periods 0-6 h and 0-24 h. The two higher doses of granisetron (1.0 mg and 3.0 mg) provided effective prophylaxis against vomiting, with 78% and 77% of patients, respectively, being free from vomiting in the first 6 h after surgery, and 63% and 62% in the first 24 h. This compares with 50% and 34% at 0-6 h and 0-24 h, respectively, in the placebo group. Granisetron was well tolerated and the optimum dose was 1.0 mg.

The fractional post-coital test performed in a square capillary tube.

A new method of examination of post-coital cervical mucus was developed, with special attention to the moving spermatozoa. The test is performed in a square capillary tube (edge 0,8 mm). The migration rate, -- velocity and -- direction are measured by means of an ocular micrometer, which is seen projected over the capillary tube.