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The production of leukaemia inhibitory factor by human endometrium: presence in uterine flushings and production by cells in culture.

The concentration of leukaemia inhibitory factor (LIF) was measured in uterine flushings obtained from normal fertile women, from women with unexplained infertility and from women who suffered recurrent miscarriage. In normal fertile women, LIF was not detected in flushings obtained on days luteinizing hormone (LH)+0 to LH+6 of the cycle, but concentrations gradually increased from day LH+7 to a maximum at day LH+12. The amount of LIF in flushings obtained from women with unexplained infertility was significantly lower than in those from normal fertile women on day LH+10 (P < 0.05). The production of LIF by cultured human epithelial and stromal cells was also investigated. LIF was not detectable in the supernatants of cultured stromal cells. Basal LIF production by epithelial cells varied according to the stage in the cycle at which the biopsy was taken. Significantly more LIF was produced by epithelial cells from late proliferative and early secretory endometrium compared with amounts produced by cells from early proliferative (P < 0.001) and late secretory (P < 0.01) endometrium. High doses of progesterone and oestradiol caused a small decrease in epithelial cell LIF production: the combined effect of progesterone and oestradiol (P < 0.01) was greater than the effect of either steroid alone (P < 0.05). The results show, for the first time, the capability of human endometrium to produce LIF in vivo. The fact that maximum LIF concentrations are present at implantation and that decreased concentrations occur in women with unexplained infertility suggest the importance of this cytokine in embryo implantation.

Cells, Cultured↗

Leukaemia inhibitory factor and interleukin 11 levels in uterine flushings of infertile patients with endometriosis.

BACKGROUND: Exact aetiology of infertility in stage I/II endometriosis patients is not known. Interleukin 11 (IL-11) and leukaemia-inhibitory factor (LIF) are factors associated with implantation window in human eutopic endometrium. We decided to test whether there is an altered secretion of these factors, which could explain receptivity defect in patients with minimal endometriosis. METHODS: Uterine flushing and endometrial samples were collected 7-9 days after ovulation (implantation window) from infertile patients with stage I/II endometriosis (n = 14) and fertile, endometriosis-free controls (n = 21). IL-11 and LIF were assessed in uterine flushings in eutopic endometria in all patients by enzyme-linked immunosorbent assay (ELISA). In eutopic endometrium, semiquantitative RT-PCR was performed for LIF and IL-11 mRNA expressions. RESULTS: No statistically significant differences were found in uterine flushing in women with and without endometriosis with regard to IL-11 levels (0.0 pg/ml versus 0.0 pg/ml) and LIF (25.53 pg/ml versus 36.26 pg/ml). These results were confirmed by the results of RT-PCR, where there were also no differences between studied groups. CONCLUSIONS: There is no receptivity defect with regard to LIF and IL-11 secretions by eutopic endometrium in infertile women with endometriosis.

Adult↗

Is follicular flushing necessary for oocyte retrieval? A randomized trial.

A prospective randomized trial was performed to evaluate the necessity of follicular flushing during transvaginal, ultrasonically guided oocyte recovery under mild sedation. Patients with tubal damage as the sole cause of their infertility were randomized into one of two groups. Group one had their follicles aspirated only. Follicles of patients in Group 2 were aspirated and flushed with a total of 10 ml of flushing medium. There was no significant difference in the number of oocytes retrieved, fertilization rate or pregnancy rate in each group. There was, however, a significant shortening of operating time in the aspiration only group.

Adult↗

Ovine trophoblast protein-1 and bovine trophoblast protein-1 are present as specific components of uterine flushings of pregnant ewes and cows.

A rabbit antiserum raised against ovine trophoblast protein-1 (oTP-1) was used to stain Western blots of the protein components from the uterine flushings of pregnant ewes (n = 61), non-bred cyclic ewes (n = 22), bred-but-nonpregnant ewes (n = 36), pregnant cows (n = 34), and bred-but-nonpregnant cows (n = 15). Nonpregnant animals were defined as ones from which no embryo was recovered. Uterine flushings of pregnant ewes contained oTP-1 between Days 14 and 24 of pregnancy, but not at Day 12. All of the cyclic ewes and 34 of 36 bred ewes, judged as nonpregnant, tested negatively for the presence of oTP-1. With one exception, oTP-1 was not detected in the nongravid uterine horns of pregnant ewes in which the conceptus had been confined to one uterine horn. Bovine trophoblast protein-1 (bTP-1), which cross-reacts immunologically with oTP-1, was also detectable specifically in the uterine flushings of pregnant cows when anti-oTP-1 antiserum was used. The urine (n = 14) and certival mucus (n = 20) samples of all the pregnant ewes tested were free of any detectable oTP-1. Thus, a useful pregnancy test for ewes based on oTP-1 release into these fluids seems unlikely. Results of this study show that oTP-1 and bTP-1 are pregnancy-specific proteins that are secreted into the uterine lumen where they possibly exert a local response.

Animals↗

The impact of saline flush of the epidural catheter on resolution of epidural anesthesia in volunteers: a dose-response study.

UNLABELLED: We evaluated the effect of 1, 20, and 40 mL of epidural saline flush on recovery from lidocaine epidural anesthesia. Eight volunteers were studied for three study periods, each separated by 72 h. The volume of saline was randomized, and a new catheter was inserted for each study period. A standardized dose of 20 mL of 2% plain lidocaine was injected for 10 min, followed by an epidural saline flush 30 min later. Sensory block was assessed by pinprick and transcutaneous electrical stimulation and motor block by a modified Bromage scale and isometric maximal force contraction. Times to void and ambulate independently before discharge were recorded. Peak plasma lidocaine concentrations and time to peak concentration were determined. Results from six volunteers showed that epidural saline, 40 mL, significantly altered anesthetic resolution, accelerating the time of complete sensory and motor block regression (P < 0.05). Median peak levels of sensory and motor block and times to void and ambulate were similar among treatment groups. Peak plasma lidocaine concentrations were similar in all treatment groups. Our data suggest that a 40-mL epidural saline injection 30 min after the induction facilitates regression of epidural lidocaine anesthesia, but a 20-mL bolus does not. Epidural saline injection does not affect vascular absorption of epidural lidocaine. IMPLICATIONS: Epidural catheter flushing with 40 mL of saline, after establishment of epidural lidocaine anesthesia, can facilitate sensory and motor block recovery. However, this does not affect vascular absorption of epidural lidocaine.

Absorption↗

Abdominal multidetector row computed tomography: reduction of cost and contrast material dose using saline flush.

OBJECTIVE: To evaluate the potential of a saline solution flush after the contrast material bolus in abdominal multidetector row CT (MDCT) in contrast material dose and cost reduction. METHODS: Abdominal MDCT was performed in 78 patients who were assigned randomly to 2 groups receiving 120 mL nonionic contrast material (300 mgI/mL) alone or 100 mL of the same contrast material pushed with 40 mL of saline solution. Mean attenuation values for both groups were measured in the liver, the spleen, the pancreas, the portal vein, the inferior vena cava, and the abdominal aorta. Cost analyses were performed for both groups. RESULTS: There was no significant difference in parenchymal and vascular enhancement between both groups. The difference of the enhancement was 2 HU for the liver (P = 0.11), 2 HU for the spleen (P = 0.44), 3 HU for the pancreas (P = 0.38), 9 HU for the portal vein (P = 0.11), 3 HU for the inferior vena cava (P = 0.55), and 10 HU for the aorta (P = 0.06). Taking the costs of contrast material, saline solution, and disposal material into account, 7.30 dollars was saved by the patient using a saline solution flush. CONCLUSIONS: Using a saline flush after the contrast material bolus in abdominal MDCT allows an iodine dose reduction of approximately 6 g, or 17%, without impairing mean parenchymal and vascular enhancement and a cost reduction of 7.30 dollars per patient.

Aged↗

Benzyl alcohol interference from heparin lock flush solutions in a high pressure liquid chromatographic procedure for mezlocillin.

During the course of a pharmacokinetic study of the antibiotic mezlocillin, we observed an interfering peak in the high pressure liquid chromatographic analytical procedure that was identified as benzyl alcohol. The benzyl alcohol interferent was traced to a preservative in heparin and saline solutions used to flush heparin locks and indicated that the heparin lock purge volume was inadequate to clean the flushing solution. The present study uses this as a model to study the amount of dilution and contamination interference observed in a controlled study where the purge volume was varied for two "real situation" concentrations of benzyl alcohol in the flush solution. It was found that only 0.5 ml of purge must be drawn to avoid significant contamination interference if benzyl alcohol-free saline is used for dilutions. Contamination interference from benzyl alcohol can also be avoided by spectroscopic or chromatographic resolution if the interference is identified and the particular analyte in question can be resolved. The results of this study provide valuable information for any study in which heparin locks are used and especially in procedures where benzyl alcohol may interfere with the method of analysis. If saline containing benzyl alcohol is used for the dilution of heparin solutions, 1.0 ml of purge must be drawn.

Benzyl Alcohol↗

Evaluation of citrate flushing solution using the isolated perfused rat kidney.

The isolated rat kidney perfused at 37 C with dialyzed bovine serum albumin (6.5 g/100 ml) in Krebs-Henseleit buffer was used to examine why a hypertonic citrate flush permits rapid recovery of renal function after storage. The composition of the original hyperosmolar citrate solution was varied so that the roles of osmolality, magnesium, and citrate could be evaluated. All kidneys were flushed with the test solutions and stored for 24 hr in the test solutions at 0 C. The citrate flushing solution requires both the citrate anion and magnesium for efficacy. Hyperosmolality does not enhance its action, an isosmolar solution is more effective. Citrate can be replaced by a nonmetabolizable analogue, tricarballylate, if the solution is suitably buffered. The mechanism of action of citrate is still uncertain, it does not seem primarily to act as a metabolic fuel or inhibitor.

Animals↗

Human kidney preservation by intracellular electrolyte flush followed by cold storage for over 24 hours.

Many transplant teams are reluctant to accept kidneys preserved with intracellular electrolyte flushing followed by simple cold storage when preservation time exceeds 24 hr. This study from one center is a comparison of 63 primary cadaver kidney grafts preserved with Collins 2 solution flush followed by cold storage for 9 to 23 1/2 hr to 42 primary cadaver kidney grafts preserved by the same method for 24 to 44 1/2 hr. Kidneys cold-stored for over 24 hr had a significantly increased requirement for dialysis in the first week following transplantation (55% versus 30%). One-month serum creatinine nadirs and actuarial graft survivals were not significantly different. Cadaver donor methylprednisolone (30 to 60 mg/kg) 2 to 9 hr prior to kidney removal reduced the requirement for first-week hemodialysis in the kidneys cold-stored for over 24 hr (23% versus 69%, P under 0.05). A human kidney preserved by the same method and cold-stored for 61 hr was successfully transplanted into a 38-year-old myelodysplastic. Satisfactory human kidney preservation can occur with intracellular electrolyte flush solutions followed by cold storage for over 24 hr when the warm ischemia time is very short.

Cold Temperature↗

Low-dose danaparoid sodium catheter flushes in an intensive care infant suffering from heparin-induced thrombocytopenia.

OBJECTIVE: Despite controversy about whether peripheral and central venous catheters should be locked with heparin to prevent catheter-associated clotting, the practice is widespread. We describe a severe side effect of the practice: a case of heparin-induced thrombocytopenia occurring with catheter flushes using unfractionated heparin (UFH) in a 10-month-old boy successfully treated with danaparoid. Patient: A preterm-born patient (33 wks gestational age, birth weight 1200 g) suffering from VACTERL syndrome was repeatedly treated with UFH in the context of several invasive procedures. On day 310 of age, a central venous catheter was inserted to provide total parenteral nutrition. The central catheter was flushed with a continuous infusion of UFH at 100 U/day, and a decrease in platelet counts from 150,000/&mgr;L (on day 310 of age) to 45,000/&mgr;L (on day 319 of age) was observed. Clinically suspected heparin-induced thrombocytopenia (HIT) was serologically confirmed by demonstrating HIT antibodies with platelet factor 4/heparin complex specificity. Main Result: Catheter flushing was switched to low-dose danaparoid sodium as a continuous infusion at 15 anti-factor Xa units per day. Two days later, platelet counts recovered. Neither catheter thrombosis nor systemic thromboembolic complications occurred during the follow up period. CONCLUSIONS: Even continuous infusion of low-dose heparin to provide patency of central venous port catheters may trigger the primary immune response of HIT. Low-dose danaparoid sodium, a heparinoid, can prevent in-catheter thrombus formation and allows normalization of platelet counts in acute HIT.

Journal Article↗

Aortoiliac enhancement during computed tomography angiography with reduced contrast material dose and saline solution flush: influence on magnitude and uniformity of the contrast column.

RATIONALE AND OBJECTIVES: To compare the magnitude and uniformity of aortoiliac contrast enhancement obtained from uniphasic contrast material injections versus contrast material injections with reduced iodine dose followed by a saline flush in aortoiliac multislice CT angiography (CTA). METHODS: Twenty-nine patients with abdominal aortic aneurysms underwent aortoiliac CTA using protocols A and B. With protocol A, 120 mL contrast material (300 mgI/mL), and with protocol B, 100 mL contrast material followed by a 40-mL saline solution flush were administered at a flow rate of 4 mL/s. Quantitative analysis was performed by calculating mean aortoiliac attenuation, mean plateau deviation, and mean difference between maximum and minimum attenuation value for both groups. Qualitative analysis was performed by visual assessment of vascular enhancement using 2-dimensional and 3-dimensional postprocessing techniques. RESULTS: The mean aortoiliac attenuation with protocol A was 291 +/- 62 HU, and with protocol B it was 285 +/- 61 HU. The difference of 6 HU was not statistically significant (P = 0.27). Mean plateau deviation was significantly smaller using protocol A than protocol B (16 +/- 9 HU vs. 20 +/- 10 HU, P = 0.03). In addition, the mean difference between maximum and minimum attenuation value was significantly smaller with protocol A than with protocol B (59 +/- 29 HU vs. 72 +/- 32 HU, P = 0.01). Visual analysis showed no difference in contrast material magnitude and homogeneity between the protocols. CONCLUSIONS: In aortoiliac CTA, a saline solution flush after contrast material bolus allows an iodine dose reduction of approximately 20 mL without impairing the magnitude of contrast enhancement but degrades the uniformity of the contrast column. However, the degradation does not affect visual analysis.

Aged↗

Chlorpropamide-alcohol flushing and blood kinins.

In a pilot study six patients with noninsulin dependent diabetes, three positive and three negative to chlorpropamide-alcohol flushing (CPAF), were tested. The patients were tested both without and with chlorpropamide premedication. Blood kinin concentrations were determined before and after ingestion of small quantities of alcohol. No rise in blood kinin concentrations were found during the flush suggesting that kinins do not play a major part in chlorpropamide-alcohol flushing.

Alcohol Drinking↗

The endocrine evaluation of three children with vasomotor flushes following hypothalamic surgery.

Although vasomotor instability or hot flushes are a well-known occurrence in women with natural or artificially-induced menopause, they have not previously been described in children. We report three children in different stages of puberty who developed vasomotor instability following surgery involving the hypothalamic-pituitary region. One, a 16 7/12 year old female with Tanner III breast development, had low oestradiol levels both pre- and post-operatively, but developed vasomotor symptoms only in the post-operative period. The second, a 12 4/12 year old boy, was sexually mature and had normal male levels of testosterone and total oestrogen when he developed hot flushes post-operatively. The third case, a boy, was prepubertal at the time of craniopharyngioma resection. Our results support the conclusion that neither oestrogen deficiency nor gonadotrophin excess are absolute requirements for the development of hot flushes. It is possible that either pressure-related factors or actual manipulation of the hypothalamic-pituitary region result in biochemical changes which result in the development of post-operative vasomotor instability in these children.

Adolescent↗

Chlorpropamide-alcohol flushing is not useful for individual genetic counseling of diabetic patients.

The presence or absence of chlorpropamide-alcohol flushing (CPAF) was not correlated with the classification of diabetes. Five out of twelve patients with juvenile-onset diabetes (JOD) flushed and three out of four patients with maturity-onset diabetes in young people (MODY) did not flush. Consequently, CPAF cannot be used for individual genetic counseling in diabetes mellitus.

Adolescent↗

Improved renal preservation with PB-3 flush solution during 72 h of cold storage.

Previously, PB-2 flush solution has been found to be superior to Collins 2 solution (C-2) in extending renal viability in the dog. To further characterize preservation mechanisms, we studied mitochondrial oxidative function during 72 h of cold storage comparing PB-3, UW-1, and C-2 flush storage solutions. Complex 1 dependent mitochondrial oxidative phosphorylation (MOP) was found to be significantly less (P < 0.001) at 5 h and 72 h of cold storage (P < 0.001) for the C-2 compared to the other flush groups. Complex 2 dependent MOP had parallel results, having significantly less function (P < 0.002) at 5 h and 72 h (P < 0.02) of cold storage in the C-2 group compared to the other groups. PB-3 and UW-1 solutions were noted to be comparable, suggesting possible equivalent preservation efficacy. Nevertheless the components of PB-3 at the level of MOP contributed significantly to better preservation compared to C-2 solution.

Adenine Nucleotides↗

Menopausal hot flushes: a double blind comparison of placebo, ethinyl oestradiol and norgestrel.

A double blind crossover study was planned in order to compare the effects of oestrogen, progestogen and placebo on hot flushes. The 49 women studied had previously undergone hysterectomy and bilateral oophorectomy. The drug regimen consisted of three months each of ethinyl oestradiol 50 microgram/day, d norgestrel 250 microgram/day, a combination of these two substance ("Nordiol") and a placebo. The predominant reason for requesting a change of medication was intolerable hot flushes associated with placebo use. All hormonal preparations were found to be significantly more effective than placebo in reducing hot flush frequency and intensity. Oestrogen containing medications were more effective than the progestogen (norgestrel).

Adult↗

Effect of intravenous clonidine on menopausal flushing and luteinizing hormone secretion.

The effect of clonidine (0.075 mg given intravenously) on subjectively experienced menopausal flushes, skin temperature and luteinizing hormone (LH) secretion was investigated in eight women in a double-blind, saline-controlled cross over study. Subjects were monitored over a 5-hour period. The number and magnitude of temperature peaks (increment greater than 1 degree C) was unaffected by clonidine. Clonidine significantly decreased the number of subjectively experienced flushes as well as the intensity of the flushes. Clonidine had no effect on the number of LH secretory pulses or on total LH secretion. These results indicate that the therapeutic effect of clonidine is independent of factors responsible for episodic skin temperature changes or factors regulating LH secretion.

Climacteric↗

A prospective study comparing the outcome of oocytes retrieved in the aspirate with those retrieved in the flush during transvaginal ultrasound directed oocyte recovery for in-vitro fertilization.

OBJECTIVE: To study prospectively the fate of oocytes collected from the follicular aspirate and subsequent flushes during transvaginal ultrasound directed oocyte recovery for in-vitro fertilization (IVF). SETTING: A tertiary referral assisted conception centre. SUBJECTS: 100 consecutive patients undergoing 100 cycles of IVF. Four patients were withdrawn because their embryos were electively cryopreserved. Therefore 96 cycles were studied. MAIN OUTCOME MEASURES: The oocyte recovery rate, viability, fertilization and cleavage rates and outcome of embryos generated from oocytes that were obtained from either the initial aspirate (A1), dead space in the collecting system (A2) or the first two 2 ml flushes (F1 and F2) were compared. RESULTS: The overall oocyte recovery rate was 87.8%. Of the 1046 oocytes collected, 40.3% were from A1, 41.3% from A2, 13.7% from F1 and 4.7% from F2. There were comparable numbers of viable and fertilized oocytes and cleaved, transferred and frozen embryos in tubes A1 and A2 but all these parameters were significantly lower in tubes F1 and F2 (P < 0.0001). All these parameters were also significantly higher in F1 compared with F2 (P < 0.001), except for the number of embryos frozen, in which there was no difference. The overall pregnancy rate per cycle was 28.1% and the pregnancy rate per embryo transfer was 31.0%. There were no pregnancies in any of the cycles in which embryos originating from F2 were transferred, nor were there pregnancies in cycles in which only embryos from F1 were transferred. CONCLUSION: Follicular aspiration together with one 2 ml flush maximises the recovery of oocytes that will result in pregnancies.

Adult↗