Expression of nitric oxide synthases in subcutaneous adipose tissue of nonobese and obese humans.

Studies have shown evidence of production of nitric oxide (NO) in adipose tissue, as well as inhibition of lipolysis by NO. We have analyzed nitric oxide synthase (NOS) expression in subcutaneous adipose tissue from 13 nonobese and 18 obese male subjects. Using a competitive reverse transcription polymerase chain reaction method, endothelial (eNOS) and inducible (iNOS), but not neuronal (nNOS), nitric oxide synthase mRNA expression was detected in isolated fat cells and pieces of adipose tissue. Tissue mRNA levels for eNOS were 3,814 +/- 825 and 5,956 +/- 476 amol/mg RNA (P = 0.043), and for iNOS 306 +/- 38 and 332 +/- 48 amol/mg RNA, for nonobese and obese individuals, respectively. Western blotting revealed similar eNOS protein levels in isolated fat cells and adipose tissue pieces. Protein levels for eNOS in nonobese and obese individuals, respectively, were (in optical density [OD] units per mm(2) per 100 microgram of total protein) 0.11 +/- 0.08 and 2.80 +/- 1.30 (P = 0.043). iNOS protein was detectable, but not measurable, at low levels in a subset of obese patients (3 of 10). iNOS protein levels could not be detected in nonobese individuals. Hormone-sensitive lipase (HSL), the key regulating enzyme in lipolysis, is reduced in obesity. The expression of HSL protein in subcutaneous adipose tissue was studied in the same subset of patients; in agreement with previous results, HSL levels were reduced in obese subjects: 4.64 +/- 1.10 and 1.27 +/- 0.35 (P = 0.012) in nonobese and obese subjects, respectively. In conclusion, this study shows that eNOS and iNOS, but not nNOS, are present in human subcutaneous adipose tissue. Gene expression and protein levels of eNOS are increased, whereas HSL protein levels are decreased in obesity. It is speculated that increased NO production, preferably by eNOS, and decreased HSL levels may cause decreased subcutaneous adipose tissue lipolysis in obesity. synthases in subcutaneous adipose tissue of nonobese and obese humans.

Preoperative infiltration of bupivacaine--effects on pain relief and trauma response (cortisol and interleukin-6).

HYPOTHESIS: Subcutaneous infiltration of bupivacaine before skin incision can reduce postoperative pain and modulate the stress response. METHODS: In a randomized study on pain relief after hysterectomy 29 patients were referred into one of three groups, receiving 30 ml of bupivacaine 0.25% with adrenaline, 30 ml of saline or no infiltration along the line of the proposed incision 10 min before start of surgery. A Visual Analogue Scale was used for repeated pain ratings. Postoperative pain relief was provided with patient-controlled analgesia with intravenous morphine 0.04 mg/kg. Lockout time was 10 min. The immunological and endocrine stress response to trauma was reflected by blood interleukin-6 (IL-6) and cortisol concentrations measured during 72 h following skin incision. RESULTS: There were large individual variations in the accumulated postoperative consumption of morphine at 20 h after start of surgery. It was significantly reduced in patients receiving infiltration of bupivacaine. They used 39 mg (9-62) median (range) of intravenous morphine whereas the patients in the saline group used 65 mg (47-120) and patients in the control group used 54 mg (36-130) (P < 0.05). Significant elevation of plasma IL-6 and serum cortisol levels appeared in all groups with peak values at 3 h. There were no differences between the groups. There was a correlation between cortisol and IL-6. Six of the 29 patients had a postoperative infection which was reflected in increased IL-6 levels. CONCLUSION: Preoperative subcutaneous infiltration of bupivacaine significantly reduced the postoperative consumption of intravenous morphine.

Extradural morphine gives better pain relief than patient-controlled i.v. morphine after hysterectomy.

We examined if patient-controlled analgesia (PCA) with i.v. morphine provided comparable postoperative analgesia after hysterectomy as extradural morphine, without increasing the incidence of side effects. The study (n = 40) was randomized and double-blind. An extradural catheter was inserted before surgery and anaesthesia was standardized. The extradural group received extradural morphine 0.06 mg kg-1 by the end of surgery and a second dose 6 h later. The i.v. group received an i.v. infusion of morphine 0.2 mg kg-1 after surgery. PCA with morphine 0.04 mg kg-1 i.v. was used in both groups. Pain relief (VAS), side effects and cognitive functions were evaluated for 18 h. Plasma samples were obtained for analysis of morphine concentrations. Mean consumption of PCA morphine was 2.4 mg h-1 for the i.v. group and 1 mg h-1 for the extradural group. Despite unlimited access to morphine, the i.v. group had higher VAS scores as the extradural group (P < 0.001). Plasma concentrations of morphine varied 8-10-fold in both groups. In the i.v. group itching, tiredness, blurred vision and vertigo correlated with cumulative consumption of i.v. morphine whereas in the extradural group this correlation existed only for tiredness. Both groups showed reduced ability to perform tests of cognitive function, indicating a central effect of both i.v. and extradural morphine, despite markedly lower plasma morphine concentrations in the extradural group.

Hormonal patterns in postmenopausal women during gynecological surgery.

The endocrine effects of surgical trauma are incompletely understood. We have measured serum levels of cortisol, 17 alpha-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHA), 4-androstene-3,17-dione (A4) and total (free + conjugated) estrone (tE1) before, during and up to 6 days after surgery in 30 postmenopausal women undergoing repair of vaginal prolapse. Anesthetic procedures were standardized. During surgery and the early postoperative hours the serum steroid pattern closely resembled that found during a diagnostic ACTH challenge test with a simultaneous increase in all adrenocortical steroids, while tE1 levels were unchanged. During the late postoperative period the levels of cortisol, 17-OHP and A4 were still elevated up to 24 h after surgery while the levels of DHA were normal or even decreased. The postoperative pattern of adrenocortical steroids may reflect a redistribution of the intra-adrenal steroid flux in favor of cortisol production. The tE1 levels were elevated in the early and, most pronounced, in the late postoperative phase. tE1 was positively correlated to A4, in the early but not in the late postoperative phase. The late increase in tE1 probably reflects an impaired bowel function in connection with surgery, leading to increased reabsorption during enterohepatic circulation.

Adrenaline, cyclic AMP and potassium during general anaesthesia with and without epidural analgesia.

Twenty patients undergoing abdominal surgery under general anaesthesia were studied to determine whether beta 2-adrenergic receptor sensitivity and adrenaline-induced hypokalaemia are related to preceding adrenergic stress. Half of the patients were given epidural analgesia with bupivacaine-adrenaline before starting surgery and then a booster dose after 60 min of surgery. The others were given only the epidural dose of bupivacaine-adrenaline at 60 min. Despite marked increases in the plasma adrenaline concentration after the intra-operative epidural dose, there was no decrease in the serum potassium concentration in either group. In the patients who received only the 60 min dose, the plasma adrenaline concentrations increased more, but the plasma level of cyclic AMP (a marker for beta 2-stimulation) increased similarly, which suggests that beta 2-adrenoceptor responsiveness was somewhat reduced. After the intraoperative bupivacaine-adrenaline, the T wave amplitude decreased, but neither U waves nor tachycardia developed. In conclusion, adrenergic stimulation during surgery does not decrease the serum potassium concentration, regardless of whether the surgical stress response has been modified by epidural analgesia. This lack of a hypokalaemic effect might be partly due to reduced responsiveness of beta 2-adrenoceptors to adrenaline.

Induction of abortion in early pregnancy with mifepristone in conjunction with gemeprost.

This study was performed to investigate the efficacy of oral mifepristone and vaginal gemeprost for termination of early pregnancy. Eighty women requesting first trimester abortion and with amenorrhea of less than 56 days were included. Gestational age was confirmed with ultrasonography. Mifepristone was administered as a single 600 mg dose followed after 48 hours by a vaginal pessary containing 1 mg gemeprost. One woman did not return for gemeprost and later had a vacuum aspiration performed. There was complete abortion in all remaining women. No serious side effects were registered and the number of women requiring opioid analgesia was low (8%). The conclusion is that this treatment is a genuine alternative to vacuum aspiration but medical supervision is necessary for some time after gemeprost administration.

PIP: Physicians at Huddinge University Hospital in Stockholm, Sweden, administered a 600 mg dose of mifepristone (RU-486) then a vaginal pessary of 1 mg gemeprost ( a prostaglandin analogue) 48 hours later to 80 healthy 18-46 year old women requesting 1st trimester abortion (gestational age = 56 days). The physicians wanted to determine the side effects and efficacy of the RU-486/gemeprost regimen to induce abortion. 1 woman did not return for the vaginal pessary and later underwent vacuum aspiration. Just 1 woman experienced a complete abortion before gemeprost treatment. The remaining 78 women experienced complete abortion after gemeprost treatment. Uterine bleeding began immediately for 26 women and on days 1 an 2 for the remaining 52 women. It lasted from 3 to 17 days. Even though most women suffered some pain after gemeprost treatment, just 6 women (8%) needed to take an opioid analgesic. The mean hemoglobin level fell significantly on day 7 (from 127 to 123 g/l; p .01), but essentially returned to preabortion levels by day 14. None of the women needed a blood transfusion. Blood loss was comparable to that of vacuum aspiration. None of the women experienced severe side effects. These findings indicated that termination of early pregnancy with RU-486 and gemeprost is an acceptable option to vacuum aspiration. This regimen should be administered under close medical supervision just in case women need analgesia and to detect the few treatment failures.

The effect of mediolateral episiotomy at delivery on pelvic floor muscle strength evaluated with vaginal cones.

In a prospective study, pelvic floor muscle strength was investigated pre- and post partum in 87 women with uncomplicated pregnancies. Those vaginally delivered were 71 primiparas, while 16 underwent an elective cesarean section. The objective was to evaluate the effect of the delivery procedure on the pelvic floor muscle strength with the aid of vaginal cones. In the group of women with vaginal delivery three subgroups were identified: episiotomy, spontaneous laceration and intact perineum. Pelvic floor muscle strength was weakest in the episiotomy subgroup, the difference in values between this subgroup and each of the other subgroups and the elective cesarean section group being significant. No significant difference was evident between the spontaneous lacerations and intact perineum subgroups.

The use of episiotomy in primiparas in Sweden. A descriptive study with particular focus on two hospitals.

This study has examined the use of episiotomy (Ep) in primiparas on all labor wards (65) in Sweden, focusing on two hospitals in particular. The information was obtained by means of a questionnaire and from original medical records at the two hospitals. Whereas the mean incidence of Ep for the whole country was 30%, we found a wide variation (9-77%) from hospital to hospital. When delivery positions were compared, the lowest Ep rate was reported from those hospitals where women frequently used "alternative positions". The results suggest that efforts should be directed to a more restrictive use of Ep in normal delivery.

Reproductive hormones during termination of early pregnancy with mifepristone.

Thirteen women received a single oral dose of 600 mg mifepristone (RU486; Roussel-Uclaf, Paris, France) on day 0 to induce first-trimester abortion. Eleven women had a complete abortion, and 2 had a continuing pregnancy and were considered as failures. Plasma levels of human chorionic gonadotropin (hCG) increased from day 0 in all women, but dropped sharply after day 3 in women with successfully induced abortion. In these women, the levels of progesterone, 17 alpha-hydroxyprogesterone and estradiol-17 beta increased from day 0 to day 1 and then dropped. In the 2 failed inductions, the steroid levels remained virtually unchanged. In the complete abortions, the main prostaglandin F2 alpha metabolite, 15-keto-13,14-dihydro-PGF2 alpha, increased to a significant peak at day 6 followed by a significant fall to day 14. These findings supports a direct effect of mifepristone on the decidua, initiating prostaglandin synthesis. It is also suggested that there is a luteolytic effect of prostaglandin F2 alpha, as the levels of corpus luteum steroids started to fall before the drop in hCG.

Induction of abortion in early pregnancy with mifepristone.

Seventy women requesting first trimester abortion and with amenorrhea of less than 42 days were treated with a single 600-mg dose of mifepristone. Mifepristone is a synthetic 19-norsteroid with strong progesterone receptor antagonist properties. Complete abortion was achieved in 56 women (80%), 2 women (3%) had an incomplete abortion and 12 women (17%) had a continuing pregnancy. No relationship between rate of success and gestational age could be demonstrated. There was no serious side effects and the treatment was favorably received by the women concerned. It is concluded that this treatment is a safe and very acceptable alternative to vacuum aspiration for termination of early pregnancy.

Serum levels of apolipoprotein A-I, A-II and HDL-cholesterol in second half of normal pregnancy and in pregnancy complicated by pre-eclampsia.

Serum concentrations of Apolipoprotein A-I and A-II, (Apo A-1 and Apo A-II) HDL-cholesterol (HDL-C), Total Cholesterol (TC), triglycerides (TG) and lipoprotein electrophoresis were assayed serially in the second half of normal pregnancy (21 women), in pre-eclampsia (26 women) and in both groups one and six weeks after delivery. In the normal group we found increased concentrations of Apo A-I and HDL-C, which remained unaltered during pregnancy. Apo A-II was unchanged. Correlation coefficients for Apo A-II vs HDL-C and Apo A-I vs Apo A-II decreased gradually towards delivery while it remained at an elevated and unaltered level for Apo A-I vs HDL-C. The Apo A-I/HDL-C ratio was unaltered during the whole study while the Apo A-I/A-II ratio was elevated during pregnancy and the Apo A-II/HDL-C ratio was reduced. These results may indicate a gradual change in the surface structure of the HDL particle or its subfractions. In pre-eclampsia Apo A-I and HDL-C concentrations were reduced, TG was increased and Apo A-II and TC were unchanged when compared with the normal pregnancy group. A more pronounced correlation coefficient was recorded for Apo A-I vs HDL-C than for Apo A-II vs HDL-C and Apo A-I vs Apo II. The results indicate that from an atherogenic point of view normal pregnancy seems more beneficial than pre-eclampsia.

Endometrial content of prostaglandin precursors during the menstrual cycle.

Fractionated curettage was performed in 18 women with cervical intraepithelial neoplasia. Otherwise all appeared to be healthy. The histological examination showed 9 of them to have been sampled in the follicular phase and the other 9 in the luteal phase. Endometrial specimens were simultaneously taken for analysis of the fatty acid pattern of lecithin (PC) and phosphatidylethanolamine (PE) by means of gas-liquid chromatography (GLC). In the luteal phase we found increased concentrations of the total sum of essential fatty acids of the linoleic acid series both in PC and PE (p less than 0.01 in both cases). All the main fatty acid components within this series showed increased mean levels in the luteal phase but only arachidonic acid (20:4) in PE was significantly elevated (p less than 0.01). The total sum of the alpha-linolenic acid series was unaffected by the phase of menstrual cycle. These results seem to indicate that the endometrium accumulates prostaglandin precursors towards the time for menstruation.

Episiotomy and perineal trauma during childbirth.

A study was conducted to assess the frequency of episiotomy and spontaneous tears in 807 primiparas during singleton births. The incidence of episiotomy was 50%, spontaneous tears 22% and intact perineum 28%. A significantly lower frequency of episiotomy (P less than 0.001) as well as epidural anaesthesia (P less than 0.001) was found among immigrant women. There were no indications registered for 58% of the episiotomies. The non-episiotomy group experienced more clitoris/labia tears (P less than 0.01). On the other hand there was a tendency towards an increased risk for second and third degree tears, 4.2% in the episiotomy group compared to 1.7% in the non-episiotomy group (P = 0.06). Haemorrhage (greater than 600 ml) was more frequent in the episiotomy group than in the non-episiotomy group (P less than 0.001). We conclude that there is little support for the claim that episiotomy prevents tears in normal deliveries, and that the rationale for the practice of episiotomy is in need of reappraisal.

Bacterial vaginosis is not a simple ecological disorder.

Eighty-four patients with bacterial vaginosis were examined in an open randomized trial, the aim of which was to define clinical results and the microbiological panorama after topical treatment for 1 week with either an acetic acid jelly (A), an estrogen cream (B), a fermented milk product (C) or metronidazole (D). After exclusion because of chlamydia infection (15 cases) or for other reasons, 61 cases remained for complete evaluation 4 weeks after the start of treatment. Clinical cure was obtained in 3 cases out of 17 on regimen A, in 1 out of 16 on regimen B, in 1 of 14 on regimen C, and in 13 out of 14 on regimen D. The patients were conclusively either symptomless or symptomatic when examined on 113 occasions. Statistically significant reduction after treatment resulting in relief of symptoms was observed in the numbers of corynebacteria and anaerobic cocci, whereas lactobacilli increased in numbers. The instillation of high numbers of Lactobacillus acidophilus (C) into the vagina cured only 1 patient and did not influence the predominance of lactobacilli in the vagina at the follow-up examination. The difference in microbiological profile of women in symptomatic and asymptomatic conditions becomes still more apparent when the results of the present and previously published studies on the subject by the present group of investigators are combined. The symptomatic woman is significantly more often harboring corynebacteria, Gardnerella vaginalis, peptostreptococci, peptococci, eubacteria and Bacteroides species. Lactobacilli are significantly reduced in numbers. However, only 51% of our previously symptomatic, but now symptomless women show predominant growth of lactobacilli, which is less than expected for healthy women.(ABSTRACT TRUNCATED AT 250 WORDS)

Successful outcome of pregnancy complicated by giant myoma and severe heparin-induced osteopenia.

A case of giant myoma and severe heparin-induced osteopenia during pregnancy is reported. The increased risk of osteopenia with heparin treatment during pregnancy is stressed.

Acute intermittent porphyria complicated by pregnancy.

The case of a woman with acute intermittent porphyria complicated by two pregnancies is described. Both pregnancies gave an exacerbation of the disease. Premature delivery were necessary for both children due to intrauterine growth retardation. The first child died from respiratory distress syndrome, but the second child was healthy apart from transient abstinence symptoms due to pethidine given to the mother during pregnancy. The effect of pregnancy on acute intermittent porphyria is discussed.

Termination of early human pregnancy with epostane.

Fifty-six healthy women, with a gestational length of less than 49 days from the last menstrual period, who requested termination of pregnancy were treated with Epostane, a progesterone synthesis inhibitor. Epostane, which competitively inhibits the 3 beta-hydroxy steroid dehydrogenase enzyme system, was given in the dose 200 mg X 4 for seven days. Physical examination, routine laboratory screening and determination of hCG, progesterone, estradiol and cortisol was performed on days 0, 7 and 14. The treatment resulted in 84% complete abortions (90% among women completing therapy). Two women experienced vaginal bleeding only, while 7 were non-responders. Among subjective side effects nausea dominated totally and was also the reason for discontinuation in 4 cases. The average length of bleeding among women with complete abortions was 10.7 days and the decrease in hemoglobin and hematocrit was very slight. Routine laboratory values remained within the normal range. Cortisol levels were elevated on day 7 compared to days 0 and 14, but all single values were within the normal limits.

PIP: 56 healthy women, with a gestational length of 49 days from the last menstrual period, who requested termination of pregnancy were treated with Epostane, a progesterone synthesis inhibitor. Epostane, which competitively inhibits the 3 beta-hydroxy steroid dehydrogenase enzyme system, was given in the dose 200 mg x 4 for 7 days. Physical examination, routine laboratory screening, and determination of hCG, progesterone, estriadol, and cortisol were performed on days 0, 7, and 14. The treatment resulted in 84% complete abortions (90% among women completing therapy). 2 women experienced vaginal bleeding only, while 7 were non-responders. Among subjective side effects nausea dominated totally and was also the reason for discontinuation in 4 cases. The average length of bleeding among women with complete abortions was 10.7 days and the decrease in hemoglobin and hematocrit was very slight. Routine laboratory values remained within the normal range. Cortisol levels were elevated on day 7 compared to days 0 and 14, but all single values were within the normal limits.