Transversus abdominis plane (TAP) block after robot-assisted laparoscopic hysterectomy: a randomised clinical trial.

BACKGROUND: Transversus abdominis plane (TAP) block is widely used as a part of pain management after various abdominal surgeries. We evaluated the effect of TAP block as an add-on to the routine analgesic regimen in patients undergoing robot-assisted laparoscopic hysterectomy. METHODS: In a prospective blinded study, 70 patients scheduled for elective robot-assisted laparoscopic hysterectomy were randomised to receive either TAP block (ropivacaine 0.5%, 20 ml on each side) or sham block (isotonic saline 0.9%, 20 ml on each side). All patients had patient-controlled analgesia (PCA) with morphine on top of paracetamol and ibuprofen or diclofenac. For the first 24 post-operative hours, we monitored PCA morphine consumption and pain scores with visual analogue scale (VAS) at rest and while coughing. Post-operative nausea and number of vomits (PONV) were recorded. RESULTS: Sixty-five patients completed the study, 34 receiving TAP block with ropivacaine and 31 receiving sham block with isotonic saline. We found no differences in median (interquartile range) morphine consumption the first 24 h between the TAP block group [17.5 mg (6.9-36.0 mg)] and the placebo group [17.5 mg (2.9-38.0 mg)] (95% confidence interval 10.0-22.6 mg, P = 0.648). No differences were found for VAS scores between the two groups, calculated as area under the curve/1-24 h, neither at rest (P = 0.112) nor while coughing (P = 0.345), or for PONV between groups. CONCLUSIONS: In our study, the TAP block combined with paracetamol and Nonsteroidal anti-inflammatory drugs (NSAID) treatment, had no effect on morphine consumption, VAS pain scores, or frequency of nausea and vomiting after robot-assisted laparoscopic hysterectomy compared with paracetamol and NSAID alone.

Cervical intraepithelial neoplasia in pregnancy.

OBJECTIVE: To determine the progression/regression rate of cervical intraepithelial neoplasia in pregnancy and to describe the number of patients requiring treatment for cervical neoplasia during or following the pregnancy. METHODS: A retrospective analysis of 305 pregnant women with abnormal cervical cytology was performed. The colposcopic, cytologic and histologic findings of repeated examinations during pregnancy and of the subsequent examination eight weeks postpartum were registered and compared. All smears were obtained by cotton bud and Cytobrush. Colposcopy was performed using standard techniques and cervical biopsies were taken in case of colposcopic abnormalities. Endocervical curettage was omitted during pregnancy. At postpartum evaluation colposcopy, directed biopsies and endocervical curettage were performed in all cases. RESULTS: One hundred and two patients (33%) were followed only by cytology and colposcopy. The remaining 203 patients (67%) had one to four colposcopically directed biopsies during the pregnancy. Comparing the initial histology in pregnancy to the postpartum histologic evaluation 25% showed spontaneous regression while 75% of the women exhibited progression (28%) or persistence (47%) in the severity of cervical neoplasia. Two patients were treated by cervical conization in early pregnancy and 143 women (53%) were treated within the first year after the pregnancy. In the postpartum period microinvasive carcinoma was diagnosed in two patients, but no women advanced to more serious stages of cervical cancer. CONCLUSIONS: The high persistence rate of cervical intraepithelial neoplasia in pregnancy leads us to recommend a liberal use of colposcopically directed biopsies during pregnancy and to ensure a high follow-up rate in the postpartum period.

PreproVIP-derived peptides in the human female genital tract: expression and biological function.

The aim of the study was to elucidate the localization, distribution, colocalization and biological effect of preproVIP-derived peptides in the human female genital tract. Radioimmunoassays applying antisera against the five functional domains of the VIP precursor in combination with immunohistochemistry were used. The effect of preproVIP 22-79, preproVIP 111-122 and preproVIP 156-170 on genital smooth muscle activity in the Fallopian tube was investigated in vitro and compared to that of VIP. All the preproVIP-derived peptides were expressed throughout the genital tract in neuronal elements closely related to the epithelial lining, perivascular tissue and non-vascular smooth muscle. Colocalization of the peptides was evidenced by double immunostaining. In contrast to VIP, preproVIP 22-79, preproVIP 111-122 and preproVIP 156-170 did not cause a significant inhibition of smooth muscle activity. The findings indicate that tissue-specific differences in post-translational processing of preproVIP exist in the female genital tract.

Pituitary adenylate cyclase-activating polypeptide: occurrence and relaxant effect in female genital tract.

The distribution, localization, and smooth muscle effects of pituitary adenylate cyclase-activating polypeptide (PACAP) were studied in the human female genital tract. The concentrations of PACAP-38 and PACAP-27 were measured by radioimmunoassays, and both peptides were found throughout the genital tract. The highest concentrations of PACAP-38 were detected in the ovary, the upper part of vagina, and the perineum. The concentrations of PACAP-27 were generally low, in some regions below the detection limit and in other regions 1 to 5% of the PACAP-38 concentrations. Immunocytochemistry revealed that PACAP was located in delicate varicose nerve fibers that were most abundant in the internal cervical os, where they mainly seemed to innervate blood vessels and smooth muscle cells. PACAP-38 and PACAP-27 (10(-10)-10(-6) M) caused a concentration-dependent relaxation of the spontaneous activity of the nonvascular smooth muscle strips from fallopian tube and myometrium in vitro. Likewise, both peptides (10(-10)-10(-6) M) caused relaxation of nonrepinephrine (10(-6) M)-precontracted intramyometrial arteries. No effect of the PACAP sequences, PACAP-(6-27), PACAP-(16-38), and PACAP-(18-27), on fallopian tube was observed. The findings suggest a smooth muscle regulatory role of PACAP in the human female reproductive tract.

Peptide histidine valine (PHV) is present and biologically active in the human female genital tract.

The occurrence of vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM) and peptide histidine valine (PHV) in the human female genital tract was studied by means of radioimmunoassay in combination with gel chromatography. In addition, the effect of PHV on genital smooth muscle activity was investigated in vitro and compared to that of VIP. Immunoreactive VIP, PHM and PHV were present in all regions of the human female genital tract, the highest concentrations being measured in the vagina and the uterine cervix. The peptides displayed similar regional distribution and as expected from the structure of the VIP precursor molecule in which the examined peptides are contained, the molar ratio of VIP to the total PHM/PHV immunoreactivity was close to 1:1. In all regions PHV constituted 50-70% of the total PHM/PHV immunoreactivity indicating that the dibasic conversion site after PHM was uncleaved. VIP and PHV were found to be equipotent relaxants of the smooth muscle from the Fallopian tube and the myometrium. The present study indicates that PHV like PHM and VIP may act as a neurotransmitter in the human female genital tract and thus participate in the local nervous control of the reproductive functions.

Vasoactive intestinal polypeptide loses its ability to increase vaginal blood flow after menopause.

The effect of vasoactive intestinal polypeptide on vaginal blood flow was investigated in postmenopausal women. In women who were receiving hormonal replacement therapy the vasodilatory response induced by vasoactive intestinal polypeptide was identical to that of young women, whereas in postmenopausal women who were receiving no replacement therapy, the response induced by vasoactive intestinal polypeptide was absent. Plasma levels of vasoactive intestinal polypeptide and systemic cardiovascular effects were identical in the two groups.

Peptide histidine methionine (PHM) increases vaginal blood flow in normal women.

The effect of increasing doses of PHM given subepithelially or intravenously on vaginal blood flow was studied. Vaginal blood flow was measured by a heated oxygen electrode, and the concentration of PHM in peripheral plasma was monitored radioimmunochemically. Injection of PHM induced a significant dose-dependent increase in vaginal blood flow. The flow values correlated with the plasma concentrations independent of the way of administration. The efficacy was the same as previously found for VIP but the potency of subepithelially injected PHM was found to be 10-fold lower than that of VIP. In conclusion, PHM and VIP seem to have similar vasodilatory effects upon vaginal blood flow.

Vasoactive intestinal polypeptide and human vaginal blood flow: comparison between transvaginal and intravenous administration.

1. The present study was performed to examine and compare the effect of increasing doses of vasoactive intestinal polypeptide (VIP) on vaginal blood flow following vaginal subepithelial and intravenous injection in normal women. 2. Local vaginal blood flow was measured by a heated oxygen electrode. 3. Peripheral blood samples were collected throughout the experiments for VIP analysis by radioimmunoassay. 4. Both subepithelial and intravenous injections induced a significant and dose-dependent increase in vaginal blood flow (P less than 0.05), displaying the same efficacy, potency and sensitivity. 5. The vaginal flow values correlated with the corresponding plasma VIP concentrations after both routes of administration. 6. The systemic vascular side effects; that is, flushing, hypotension and tachycardia, were observed following both subepithelial and intravenous injection. 7. The findings indicate that the effect of VIP on vaginal blood flow irrespective of route of administration is part of a systemic vasodilatory effect rather than a local response.

Peptide histidine methionine and vasoactive intestinal peptide: occurrence and relaxant effect in the human female reproductive tract.

The occurrence of the neuropeptides peptide histidine methionine (PHM) and vasoactive intestinal peptide (VIP) in the human female genital tract was studied by means of immunochemistry and radioimmunoassay in combination with gel chromatography. In addition, the effect of PHM and VIP on smooth muscle activity was investigated in vitro. The regional distribution of PHM as determined by radioimmunoassay correlated with that of VIP. This finding agreed with the immunohistochemical data, which, in addition, provided evidence for colocalization of the two peptides in nerve fibers. These fibers were most abundant in the vagina and the uterine cervix, where they seemed to innervate blood vessels, smooth muscle, and epithelial cells. The concentrations of immunoreactive PHM and VIP were found to be similar in all areas except in the vagina, where the PHM concentration was fourfold that of VIP. Gel chromatography of vaginal extract revealed a high concentration of a C-terminally extended form of PHM, suggesting differential processing pathways of the VIP precursor. Both PHM and VIP inhibited, in a dose-dependent manner, the smooth muscle activity in strips from the Fallopian tube and the myometrium. Administered in combination, PHM and VIP had an additive effect and displayed the same efficacy as VIP alone, indicating that the peptides act via a common receptor.

Non-amidated forms of VIP (glycine-extended VIP and VIP-free acid) have full bioactivity on smooth muscle.

The aim of the present study was to elucidate the importance of the C-terminal amide group for the biological activity of vasoactive intestinal peptide (VIP). Two synthetic peptides lacking the amide group: VIP having a carboxyl group at the C-terminus and the intermediate biosynthetic precursor, glycine-extended VIP were compared with VIP itself regarding the ability to inhibit spontaneous activity in smooth muscle strips from rat stomach and human Fallopian tube. Both the glycine-extended VIP and VIP having a carboxyl group at the C-terminus caused a significant and dose-dependent inhibition of smooth muscle activity and displayed dose-response curves similar to VIP. The potencies of the VIP variants did not differ significantly from that of VIP. Thus, alpha-carboxyamidation of VIP is not a prerequisite for biological activity.

Regulatory peptides in the mammalian urogenital system.

By immunocytochemistry a number of the gut/brain peptides have been demonstrated in nerve fibers of the mammalian urogenital tract. These peptides are localized to large vesicles in nerve terminals of afferent fibers or efferent nerves innervating blood vessels, non-vascular smooth muscle, lining epithelium and glands. There is evidence that some neuropeptides (VIP, NPY) participate in the local non-cholinergic, non-adrenergic nervous control of smooth muscle activity and blood flow, while other peptides (substance P, CGRP) seem to be sensory transmitters. It is likely that impaired function of the peptidergic nerves is involved in sexual dysfunction such as male impotence.

Increased risk of abortion after genetic amniocentesis in twin pregnancies.

Forty-seven twin pregnancies among 3676 patients who had a genetic amniocentesis between 1973 and 1979, are reported. The detection rate of twins at the time of amniocentesis was 62 per cent. Five (17 per cent) of the 29 women with detected twin pregnancy aborted spontaneously, these are compared with 1 (6 per cent) of 18 women with undetected twin pregnancies and with 3 (3 per cent) of 93 singleton pregnancies, selected as controls as they had amniocentesis performed immediately before and after each of the twin mothers. Two of 9 (22 per cent) twin pregnancies, who had at least two punctures in at least one sac aborted, while 3 of 20 twin pregnancies with one puncture in each sac aborted (15 per cent). One of 18 (6 per cent) twin pregnancies, where only one sac was punctured, because the twin pregnancies were undetected, aborted. Amniocentesis of both sacs in twin pregnancies seems associated with an increased risk of spontaneous abortion. The indications for amniocentesis in twin pregnancies should be critically evaluated.