Isoflurane Anesthesia Attenuates Endothelium-dependent Pulmonary Vasorelaxation by Inhibiting the Synergistic Interaction between Nitric Oxide and Prostacyclin

Background: Endothelium-derived nitric oxide causes vasodilation in part by increasing the dilator activity of other endothelium-derived mediators, including prostacyclin and a K sup +ATP channel-dependent hyperpolarizing factor. Although previous studies have proposed that isoflurane (ISO) depresses endothelium-dependent vasorelaxation by inhibiting endothelium-derived nitric oxide activity, the effects of ISO on the interactions among endothelium-derived dilators have not been characterized. The aim of this study was to determine the mechanisms underlying the inhibitory effect of ISO on endothelium-dependent relaxation in canine pulmonary arteries. Specifically, the goal was to assess the effects of ISO on the individual actions and on the synergistic interactions of these endothelium-derived mediators.

Methods: Canine pulmonary arterial rings were suspended for isometric tension recording. The effects of 1 minimum alveolar concentration ISO (0.4 mM) on vasorelaxation responses to bradykinin, A23187, acetylcholine, cromakalim, and SIN-1 were assessed in phenylephrine-precontracted rings with and without pretreatment with a nitric oxide synthase inhibitor (N sup omega -nitro-L-arginine methyl ester; L-NAME), a cyclooxygenase inhibitor (indomethacin), or a K sup +ATP, channel inhibitor (glybenclamide).

Results: Isofluane attenuated pulmonary vasorelaxation induced by bradykinin, A23187, and cromakalim but had no effect on relaxation induced by acetylcholine or SIN-1. Neither the nitric oxide-mediated nor the prostacyclin-mediated components of relaxation induced by bradykinin and A23187 were altered by ISO. However, ISO abolished the K sup +ATP -mediated component of relaxation and the K sup +ATP -dependent synergistic interaction between nitric oxide and prostacyclin.     

Long-term transdermal estradiol therapy: effects on endometrial histology and bleeding patterns.

Sixty postmenopausal women were enrolled in a 2-year randomized unmasked trial to determine the long-term safety of estradiol (E2) administration by a transdermal therapeutic system. Group I subjects received 0.1 mg of transdermal E2 for 24.5 days of each 28-day cycle for 96 weeks. Group II subjects received the same dosage of transdermal E2 plus 10 mg of medroxyprogesterone acetate, given orally from days 13-25 of each cycle. Vaginal bleeding patterns and endometrial histology were characterized. The subjects recorded bleeding patterns daily. Endometrial biopsies were performed during scheduled follow-up visits at 48 and 96 weeks or as needed to evaluate abnormal bleeding. Data were analyzed by intention to treat. Ten and four subjects dropped out of the study from groups I and II, respectively. A total of 575 and 627 treatment cycles were observed in the same respective groups. Vaginal bleeding was observed in 980 cycles: 381 of 575 cycles in group I (66.3%) and 599 of 627 cycles in group II (95.5%). Bleeding onset, duration, and quantity were similar for both groups. The incidence of hyperplasia was 42 and 4% for groups I and II, respectively, over the 96-week study period. All cases of hyperplasia in group I were treated with sequential medroxyprogesterone acetate for 12 weeks, followed by rebiopsy. In ten of 11 cases, the progestin therapy converted the hyperplasia to a normal endometrium. In one case, the endometrium became hyperplastic again at 96 weeks, but reverted to normal with 12 weeks of medroxyprogesterone acetate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gonadal protection and fecundity rates in cyclophosphamide-treated rats

Premature ovarian failure and reduced fecundity are well-documented consequences of cytotoxic chemotherapy used to treat patients with malignant diseases. To investigate the ability of different hormonal agents to block the effects of cyclophosphamide (CTX) on reproductive function, sexually mature female Long-Evans rats were studied. Model development demonstrated that CTX, 6 mg/kg/day, 5 days/week for 3 weeks, was successful at inducing acyclicity and significantly reducing fertility and fecundity, with acceptable mortality, when compared to higher/lower dosages. Utilizing this model, animals were treated with CTX in combination with an inert vehicle, Lupron, 80 micrograms/kg every 24 h, Lupron, 40 micrograms/kg every 12 h, or s.c. progesterone capsules obtaining serum progesterone levels of 20-30 ng/ml. We concluded that progesterone was able to protect the gonad from the negative effects of CTX, maintaining fertility and fecundity rates not significantly different from those of untreated control animals. Lupron given every 12 h had a similar effect on fertility, but failed to protect fecundity (P less than 0.001).     

Appropriateness of hysterectomies performed for multiple preoperative indications.

OBJECTIVE: To correlate the listing of multiple preoperative indications for hysterectomy with the risk of non-confirmation of the preoperative diagnosis. METHODS: Records of 171 women undergoing consecutive hysterectomies for all indications at a large teaching hospital were reviewed for preoperative indication(s), compliance with published preoperative validation criteria for cases in which tissue pathology was not expected, and histologic verification of the preoperative diagnosis for cases in which tissue pathology was expected. Rates of confirmation (histologic verification plus successful compliance with validation criteria) of the preoperative diagnosis were compared between subgroups of cases in which single indications were listed (N = 124) or multiple indications were listed (N = 47) preoperatively. RESULTS: The rate of confirmation of single indications (115 of 124 cases, 93%) was significantly higher than the rate of confirmation of even one indication in cases in which multiple indications were listed (28 of 47 cases, 60%, P < .0001; relative risk for non-confirmation of multiple indications = 1.55). Multiple indications were more likely to be listed when tissue pathology was not expected, representing 49% of validatable indications as compared with only 18% of histologically verifiable indications (P < .0001). Overall, the rate of compliance with validation criteria (70%) was significantly lower than the rate of histologic verification (90%) (P < .01). CONCLUSION: These data suggest that listing of multiple preoperative indications for hysterectomy is associated with both decreased appropriateness, as reflected in decreased compliance with generally accepted preoperative validation criteria, and decreased diagnostic accuracy, as reflected in lower rates of histologic verification.     

Inhibition by indomethacin of increased estradiol extraction by the IUD-containing rat uterine horn

The role of prostaglandins on the extraction of estradiol (E2) by the rat uterine horn in the presence of the intrauterine device (IUD) was evaluated. Increased extraction of E2 by the IUD horn compared to the contralateral control horn was consistently observed irrespective of the estrogen status of the animals. This increased extraction was abolished by indomethacin, an inhibitor of prostaglandin synthesis, suggesting a role of prostaglandin in this process.     

Further delineation of hypothalamic dysfunction responsible for menopausal hot flashes

An association exists between pulsatile LH release and hot flashes (HFs). To further delineate the hypothalamic mechanism(s) responsible for HF, the basal levels and pulsatile release of LH, FSH, estradiol, and estrone and the rate of occurrence of HFs (measured objectively) were evaluated in patients with a defect of GnRH secretion [isolated gonadotropin deficiency (IGD)], patients with abnormalities of afferent input to GnRH neurons [hypothalamic amenorrhea (HA)], and postmenopausal women with severe HFs. Patients with IGD had received estrogens, which were discontinued before study. Patients with HA had experienced regular menses before disease onset, which followed emotional stress or weight loss. Studies were limited to HA patients with estrogen levels in the postmenopausal range. Pulsatile LH release was absent in patients with IGD and was absent or greatly reduced in women with HA. Objectively measured and subjectively experienced HFs occurred in IGD but not in HA patients. These results suggest that HFs are not an obligatory consequence of low endogenous estrogen levels and that the absence of episodic LH and GnRH release (IGD) does not influence the occurrence of HFs. It is possible that the dysfunction of afferent input to GnRH neurons in HA somehow prevents HFs in these women with low endogenous estrogen secretion.     

Clinical predictors for mortality in adults undergoing thoracic aortic surgery requiring deep hypothermic circulatory arrest

This retrospective, observational study was performed on adult patients undergoing thoracic aortic surgery (ATAS) requiring standardized deep hypothermic circulatory arrest (DHCA) with following aims. (1). To determine the mortality rate after ATAS-DHCA (2). To determine univariate predictors for mortality after ATAS-DHCA (3). To determine multivariate predictors for mortality after ATAS-DHCA A total of 144 patients operated during 2000/2001 were included. The mortality rate was 11.1%. Univariate predictors for mortality after ATAS-DHCA were preoperative ejection fraction less than 40%, stroke, packed red blood cell transfusion within first 24 hours, sepsis, mediastinal re-exploration for bleeding within first 24 hours, and renal dysfunction. Multivariate predictors for mortality after ATAS-DHCA were sepsis (odds ratio 21.3:1; confidence interval 3.8-12.1;p=0.001), postoperative stroke (odds ratio 7.4:1; confidence interval 1.9-28.7;p=0.004) and mediastinal re-exploration within first 24 hours (odds ratio 7.7:1; confidence interval 1.3-45.1;p = 0.02) We conclude that mortality after ATAS-DHCA remains high. The identified multivariate predictors merit further hypothesis-driven intervention.     

Elements of a successful quality improvement and patient safety program in obstetrics and gynecology

In this article we present the elements of one approach to quality improvement and patient safety that we believe can be successful and sustainable in the field of obstetrics and gynecology, along with several strategies (and caveats) that have worked and are working in academic and nonacademic institutions in the United States. Also included are several noteworthy definitions of quality to provide some additional perspectives on what is meant by quality in health care.     

Nongynecologic somatic pathology in women with chronic pelvic pain and negative laparoscopy.

One hundred eighty-three women with chronic pelvic pain were referred to a multidisciplinary chronic pelvic pain clinic after negative laparoscopy. One hundred twenty-two of them completed a thorough medical and psychologic evaluation and were followed for a minimum of six months after completion of therapy. Occult somatic pathology was diagnosed in 57 women (47%), including 19 in whom coexistent psychopathology was diagnosed. Myofascial pain was the most common somatic diagnosis, followed by atypical cyclic pain (dysmenorrhea or mittelschmerz); gastroenterologic, urologic and infectious diseases; and pelvic vascular congestion. No plausible somatic etiology was apparent in the remaining 65 (53%) of the 122 referrals. Nongynecologic somatic pathology accounted for 34 (29%) and gynecologic pathology for 23 (19%) of the referrals, only 6 (5%) of whom ultimately required hysterectomy. Women with a somatic diagnosis were found to be significantly older than the remainder of the referral population. Long-term symptomatic improvement or resolution of pain was obtained in 43 (75%) of the 57 patients with somatic diagnoses. Coexistent psychopathology was found to correlate with a poorer long-term prognosis. Our findings underscore the importance of a multidisciplinary approach to evaluating and treating chronic pelvic pain in women and confirm that hysterectomy is indicated in this setting only rarely.     

Ovulation induction in women age 40 and older: the importance of basal follicle-stimulating hormone level and chronological age.

OBJECTIVES: To determine pregnancy and livebirth rates for women age 40 and older undergoing ovulation induction and to assess the impact of basal follicle-stimulating hormone (FSH) on outcome in these patients. DESIGN: Prospective, observational. SETTING: Fertility service of university medical center. PATIENTS: Infertile couples in whom the female partner was age 40 or older referred for ovulation induction therapy. INTERVENTION: Assessment of basal hormonal status; ovulation induction. MAIN OUTCOME MEASURES: Clinical pregnancy rate (PR), livebirth rate. RESULTS: Analysis of 402 cycles in 85 women age 40 and older demonstrated a clinical PR of 3.5% per cycle (95% confidence interval [CI] 1.7% to 5.3%). The livebirth rate was 1.2% per cycle (95% CI 0.1% to 2.3%). Women with a basal FSH < 25 IU/L and age < 44 years had a clinical PR of 5.2% per cycle (95% CI 2.5% to 7.9%) compared with 0.0% per cycle (95% CI 0.0% to 2.1%) in cases in which either basal FSH was > or = 25 IU/L or age was > or = 44 (P < 0.005). The prognostic importance of basal FSH and chronological age was confirmed by multivariate logistic regression analysis. The predictive value of the resulting regression equation was high (R2 = 0.94; P < 0.01). CONCLUSIONS: Pregnancy and livebirth rates are generally low during ovulation induction in women age 40 and older. In combination, basal FSH and chronological age are accurate predictors of PR, in these couples and can define a subset of patients with a more favorable prognosis. The spontaneous abortion rate in women who do conceive is high, substantially lowering the livebirth rate.