Determining the sex of bovine embryos using polymerase chain reaction results: a six-year retrospective study.

Knowing the sex of embryos produced for use in an embryo transfer program can assist the dairy producer in managing his resources more effectively. A reliable procedure for accomplishing this goal is to apply PCR technology to the biopsy of an embryo. A description is provided of how the technique has been applied on a large scale in a commercial setting in western Canada between 1992 and 1997. A total of 4,183 embryos was biopsied over a 6-yr period. The sex was determined with more than 90% of the embryos. The results showed that there was a seasonal variation in the sex ratio, with more females being recorded in the period of least light (October to March), than in April to September. While both sire and embryo quality affected the sex ratio, the differences were too small to be of value in most breeding programs. Pregnancy rates with fresh sexed embryos (58 to 71%) were comparable to those with fresh unsexed embryos. The results following freezing and thawing of sexed embryos were low (37 to 66%) but sufficient to be viable commercially. When the sex assigned by PCR was verified by fetal sexing at 60 d of gestation, the error rate was 7%. This study demonstrates that sexing of embryos can be carried out on a large scale. Demand for quick, reliable determination of sex can be met in a cost effective manner. The pregnancy rates achieved with embryos after biopsy are suitable for use in a commercial setting.

Half-life of estradiol in postmenopausal women.

Estrogen replacement is often advised for postmenopausal women to prevent menopausal symptoms, osteoporosis and heart disease. However, little information is available concerning the half-life of estradiol (E2) in postmenopausal women. This study was designed to determine the half-life and metabolism of transdermal E2. A prospective clinical study of 8 healthy postmenopausal women was performed in the Clinical Research Center of the Brigham and Women's Hospital. A transdermal E2 patch 0.10 mg was placed on the abdominal wall. Thirteen hours later, after an overnight fast, the E2 patch was removed and frequent blood sampling was performed over 6 h. Serum samples were assayed for E2, estrone (E1) and estrone sulfate (E1S). Serum samples were taken before E2 patch placement, for 30 min before patch removal, and for 6 h after patch removal. The basal E2 level of women prior to use of transdermal E2 was 19 +/- 2 pg/ml (mean +/- SE). Thirteen hours after transdermal E2 placement, steady state levels had been reached, with a mean E2 of 112 +/- 6 pg/ml. The mean half-life of E2 after removal of transdermal E2 was 161 min (range 107-221 min). There was a direct relationship between the subjects' weight and the half-life of E2 (r = 0.79, p = 0.02). Mean basal E1 levels were 23 +/- 5 pg/ml and mean E1 steady-state levels after E2 patch placement were 39 +/- 0.6 pg/ml. E1S levels rose from mean basal levels of 1.5 +/- 0.3 ng/ml to mean steady-state levels of 3.1 +/- 0.1 ng/ml after placement of the E2 patch. The apparent half-life of E2 after discontinuing a transdermal E2 patch is 2.7 h or 161 min.

Estrogen absorption and metabolism in postmenopausal women with end-stage renal disease.

Women with end-stage renal disease (ESRD) have a higher rate of death from heart disease than women with normal renal function. Because estrogen replacement therapy may significantly decrease the incidence of death due to cardiovascular disease in postmenopausal women with normal renal function, their use has been considered for women with ESRD. However, the pharmacokinetics of estrogen have not been studied in postmenopausal women with ESRD to determine the optimal estrogen dose. Six postmenopausal women with ESRD receiving maintenance hemodialysis and six controls matched for body mass index were admitted to the in-patient Clinical Research Center. A 1- or 2-mg oral estradiol (E2) pill was given while subjects fasted. Blood sampling was performed over the next 24 h for measurement of E2, estrone (E1), albumin, and sex hormone-binding globulin (SHBG). Three weeks later, the subjects were given the other E2 dose under identical conditions. At baseline, total and free E2 levels were higher in the subjects with ESRD than in controls (P = 0.0005 and 0.0035, respectively). After ingestion of 1 and 2 mg E2, total and free E2 levels remained significantly higher in the ESRD subjects from 2-8 h after treatment (P < or = 0.05). After 1 mg oral E2, total serum E2 peaked at 65 pg/mL at 4 h in ESRD subjects and at 27 pg/mL in control subjects at 8 h. After 2 mg oral E2 treatment, total serum E2 peaked at 8 h in both ESRD and control subjects, with levels of 99 and 37 pg/mL, respectively. E1 was higher in the subjects with ESRD than in the control subjects at baseline (P < 0.05). After ingestion of 1 mg E2, E1 concentrations were not significantly higher in ESRD than in control subjects, peaking at 180 and 121 pg/mL, respectively (P = 0.3). E1 concentrations were higher in ESRD than in control subjects after the ingestion of 2 mg E2, with peak levels of 376 and 201 pg/mL, respectively (P = 0.03). Total and free E2 levels are higher in patients with ESRD than in control subjects at baseline and after E2 ingestion, indicating that renal failure alters the pharmacokinetics of both endogenous and exogenous E2. Therefore, conventional E2 doses used in individuals with normal renal function may be excessive for patients with ESRD.

Treatment of supraventricular tachyarrhythmias with intravenous calcium channel blockers: are subtle differences worth the cost?

Verapamil and diltiazem are effective in terminating paroxysmal supraventricular tachycardias and slowing ventricular response during atrial fibrillation or flutter. Results from clinical trials for each individual drug demonstrate comparative efficacy rates, and both drugs share the same contraindications and relative precautions. Well-designed comparative clinical trials are needed to establish if either drug has any clinical advantages in a particular patient population.

Effects of ofloxacin administration on the reliability of urine glucose testing.

OBJECTIVE: To study the effects of ofloxacin on the reliability of urine glucose testing. DESIGN: Open-label, nonrandomized. SETTING: A university-affiliated tertiary care hospital, ambulatory clinic. PARTICIPANTS: Ten healthy volunteers (8 men and 2 women) aged 22-39 years. MAIN OUTCOME MEASURES: Phase I (in vitro) involved the addition of selected amounts of ofloxacin to a set of standard 50-mL urine samples prepared to simulate glycosuria. Phase II (in vivo) involved the oral administration of ofloxacin 400 mg to 10 subjects. Urine was collected: (1) immediately predose, (2) pooled 0-4 hours postdose, and (3) pooled 4-8 hours postdose. Known glucose concentrations were then added to these samples. Clinitest and Diastix tests were performed on all samples. The accuracy of these tests in determining glucose concentrations was compared among urine samples taken before and after ofloxacin dosing. RESULTS: None of the ofloxacin concentrations in phase I (0, 25, 50, 100, 200, 400, and 800 micrograms/mL) influenced these testing methods at the urine glucose concentrations of 0.0%, 0.5%, 1%, and 2%. Likewise, the accuracy of these two tests was unaffected by ofloxacin administration in phase II. CONCLUSIONS: In single-dose administration, ofloxacin does not interfere with Clinitest or Diastix for determining urine glucose concentrations.

Incidence of adverse drug events and potential adverse drug events. Implications for prevention. ADE Prevention Study Group.

OBJECTIVES: To assess incidence and preventability of adverse drug events (ADEs) and potential ADEs. To analyze preventable events to develop prevention strategies. DESIGN: Prospective cohort study. PARTICIPANTS: All 4031 adult admissions to a stratified random sample of 11 medical and surgical units in two tertiary care hospitals over a 6-month period. Units included two medical and three surgical intensive care units and four medical and two surgical general care units. MAIN OUTCOME MEASURES: Adverse drug events and potential ADEs. METHODS: Incidents were detected by stimulated self-report by nurses and pharmacists and by daily review of all charts by nurse investigators. Incidents were subsequently classified by two independent reviewers as to whether they represented ADEs or potential ADEs and as to severity and preventability. RESULTS: Over 6 months, 247 ADEs and 194 potential ADEs were identified. Extrapolated event rates were 6.5 ADEs and 5.5 potential ADEs per 100 nonobstetrical admissions, for mean numbers per hospital per year of approximately 1900 ADEs and 1600 potential ADEs. Of all ADEs, 1% were fatal (none preventable), 12% life-threatening, 30% serious, and 57% significant. Twenty-eight percent were judged preventable. Of the life-threatening and serious ADEs, 42% were preventable, compared with 18% of significant ADEs. Errors resulting in preventable ADEs occurred most often at the stages of ordering (56%) and administration (34%); transcription (6%) and dispensing errors (4%) were less common. Errors were much more likely to be intercepted if the error occurred earlier in the process: 48% at the ordering stage vs 0% at the administration stage. CONCLUSION: Adverse drug events were common and often preventable; serious ADEs were more likely to be preventable. Most resulted from errors at the ordering stage, but many also occurred at the administration stage. Prevention strategies should target both stages of the drug delivery process.

The effects of ethanol on the clearance of estradiol in postmenopausal women.

OBJECTIVE: To determine whether acute alcohol ingestion affects the pattern of decline of circulating E2 levels after removal of transdermal E2 patches. DESIGN: A randomized, placebo-controlled, crossover study. SETTING: The study was performed in the Clinical Research Center of the Brigham and Women's Hospital. PARTICIPANTS: Twelve healthy postmenopausal women were enrolled. INTERVENTIONS: Transdermal E2 patches, 0.15 mg, were applied 13 hours before subjects ingested alcohol (1 mL/kg 95% ethanol) or carbohydrate placebo punch. The patches were removed immediately after drink ingestion. MAIN OUTCOME MEASURES: Estradiol, estrone (E1), and ethanol levels were measured. RESULTS: Serum samples were obtained for 40 minutes before drink ingestion and 5 hours after drink ingestion and E2 patch removal. At the time of patch removal, E2 levels rose acutely over 10 minutes and then decreased rapidly, suggesting a bolus effect that was more marked after ethanol ingestion. After ethanol ingestion and patch removal the half-life of E2 was calculated to be 378 minutes, and after carbohydrate punch and patch removal 245 minutes. There were no significant changes in E1 concentrations over the time course of the study between groups. CONCLUSIONS: Ethanol ingestion may decrease E2 clearance after removal of transdermal E2 patches.

Effect of acute ethanol ingestion on prolactin in menopausal women using estradiol replacement.

Epidemiologic studies suggest that women who consume ethanol are at an increased risk for developing breast cancer. Two randomized, crossover studies were performed to examine the effects of ethanol on prolactin in menopausal women using transdermal estradiol. In study 1, transdermal estradiol patches (0.15 mg) were administered to menopausal women (n = 7) the day before ethanol administration. At 8.00 h, the women ingested ethanol (1 ml/kg, 95% ethanol) or an isocaloric carbohydrate drink. Prolactin levels were measured frequently for 6.3 h. Serum ethanol levels reached a broad peak from 40 to 100 min after initiation of ethanol ingestion. Serum prolactin levels were significantly higher after ethanol ingestion than after the isocaloric carbohydrate drink ingestion (p < 0.03). Study 2 was identical to study 1 except that the transdermal estradiol patches were removed after completion of ethanol or carbohydrate ingestion. In study 2, serum prolactin was greater after ethanol ingestion than after carbohydrate ingestion (p < 0.001). In menopausal women using transdermal estradiol, acute ethanol ingestion is associated with an increase in serum prolactin.

Stability of metoprolol tartrate in 5% dextrose injection or 0.9% sodium chloride injection.

The stability of metoprolol tartrate 0.40 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags stored at 24.0 +/- 2.4 degrees C was studied. Triplicate admixtures of each solution were prepared. A stability-indicating high-performance liquid chromatographic assay was used to determine metoprolol tartrate concentrations. At 0, 6, 12, 24, and 36 hours, samples were visually assessed then assayed in duplicate. Stability was defined as a < 10% decline in metoprolol tartrate concentration from the time 0 determination. No notable color changes or precipitation was observed in any sample. All samples demonstrated a < 7% reduction in metoprolol tartrate concentration over 36 hours. Metoprolol tartrate 0.40 mg/mL admixed in 5% dextrose injection or 0.9% sodium chloride injection in PVC bags and stored at 24.0 +/- 2.4 degrees C was stable for 36 hours.

Stability of cyclosporine with magnesium sulfate in 5% dextrose injection.

The compatibility and stability of cyclosporine with magnesium sulfate in 5% dextrose injection was studied. Cyclosporine solution 50 mg/mL was added to each of three glass bottles containing magnesium sulfate injection and 5% dextrose injection; final theoretical concentrations of cyclosporine and magnesium sulfate were 2.0 mg/mL and 30 mg/mL, respectively. The samples were stored under fluorescent lighting at controlled room temperature (24 +/- 2.4 degrees C). At 6, 12, 24, and 36 hours each solution was visually inspected under normal lighting against a white and black background for color change, haze, or precipitation. Samples were assayed in duplicate for cyclosporine concentration by using a stability-indicating high-performance liquid chromatographic method. Turbidity occurred immediately after mixing but resolved in approximately 30 seconds. No other changes in clarity or color were noted. The admixtures retained > 90% of initial cyclosporine concentration for six hours, and there were no significant differences in mean cyclosporine concentrations among the individual samples. Cyclosporine 2.0 mg/mL added to magnesium sulfate 30 mg/mL in 5% dextrose injection was stable for six hours when stored in glass bottles at 24 degrees C under fluorescent lighting.

Use of paper-absorbed fingerstick blood samples for studies of antibody to human immunodeficiency virus type 1 in intravenous drug users.

The suitability of paper-absorbed (PA) fingerstick blood specimens for antibody testing of human immunodeficiency virus type 1 (HIV-1) was examined in two populations of intravenous drug users (IVDU): 393 persons from a drop-in counseling and testing clinic and 145 from a methadone treatment clinic. From the first group, the same 66 immunoblot-confirmed enzyme immunoassay (EIA)-positive specimens were identified in sera from venipuncture and parallel fingerstick PA specimens. The latter had slightly higher EIA mean background levels resulting in 10 immunoblot-negative EIA-positive samples versus 6 in the sera group. HIV-1 seroprevalence was 17% of 393 from the drop-in clinic. By category of IVDU, the rates were 34% and 14% for active and recovering IVDU, respectively (P less than .001), and 36% in black and Latino compared with 13% in white IVDU (P less than .002). Of the 145 participants in the methadone program, 39% had antibody to HIV-1: 49% for blacks and Latinos compared with 30% in whites (P less than .01). The data indicate that antibody testing for HIV-1 by PA is equivalent to the serum antibody assay of venipuncture specimens. The fingerstick method appears to have greater use for serosurveys and screening programs because of convenience, safety, and ease of storage, transport, and processing of samples.

Stability of famotidine in a 3-in-1 total nutrient admixture.

The stability of famotidine in a 3-in-1 total nutrient admixture stored at room temperature (24 degrees C) was evaluated over 24 hours. Famotidine injection was diluted to a theoretical concentration of 20 mg/L in a total nutrient admixture containing 5% amino acid injection, 25% dextrose injection, and 2.25% intravenous fat emulsion. Admixtures were prepared in 2-L ethylene-vinyl acetate bags using conventional techniques and stored at room temperature. At 0, 4, 8, 12, and 24 hours, the admixtures were visually inspected for color change, creaming, or phase separation, and samples were obtained for assay with a stability-indicating method of HPLC, using samples obtained at time zero as controls. Two-way analysis of variance was used for data evaluation. There was no evidence of color change, creaming, or phase separation before quantitative analysis was performed, nor was there significant change in observed famotidine concentration over 24 hours. Based upon our data, famotidine intravenous solution 20 mg/L in the solution tested is stable at room temperature for 24 hours.

Ganciclovir hepatotoxicity.

A 33-year-old male with acquired immunodeficiency syndrome received ganciclovir for presumed cytomegalovirus retinitis. Although results of baseline liver function tests were abnormal, marked elevations of transaminases and alkaline phosphatase occurred when the drug was first instituted, as well as after rechallenge. These elevated laboratory values declined on each occasion that the drug was withdrawn. As no other toxic or infectious insults could clearly be incriminated in these acute, self-limited episodes of hepatic function abnormalities, ganciclovir was most likely responsible for the toxicity observed in this patient.

Acyclovir-associated fever: a case report.

Drug-induced fever has been associated with many agents. We treated a patient who developed high, spiking fevers while receiving intravenous acyclovir. Rechallenge with the drug was not attempted. Clinicians should be aware of the possibility of drug-induced fever in patients who receive systemic acyclovir.