Pharmacological activity of a Bv8 analogue modified in position 24.

BACKGROUND AND PURPOSE: The amphibian peptide Bv8 induces potent nociceptive sensitization in rodents. Its mammalian homologue, prokineticin 2 (PROK2), is strongly up-regulated in inflamed tissues and is a major determinant in triggering inflammatory pain. Bv8 and PROK2 activate two closely related GPCRs, PK(1) and PK(2) , in a relatively non-selective fashion. To characterize better the roles of the two receptors in hyperalgesia and to obtain ligands whose binding affinity and efficacy differed for the two receptors, we modified the Bv8 molecule in regions essential for receptor recognition and activation. EXPERIMENTAL APPROACH: We modified the Bv8 molecule by substituting Trp in position 24 with Ala (A-24) and compared it with Bv8 for binding and activating PK(1) and PK(2) receptors in cell preparations and in affecting nociceptive thresholds in rodents. KEY RESULTS: A-24 preferentially bound to PK(2) receptors and activated them with a lower potency (5-fold) than Bv8. When systemically injected, A-24 induced Bv8-like hyperalgesia in rats and in mice, at doses 100 times higher than Bv8. Locally and systemically injected at inactive doses, A-24 antagonized Bv8-induced hyperalgesia. In rat and mouse models of inflammatory and post-surgical pain, A-24 showed potent and long-lasting anti-hyperalgesic activity. Unlike Bv8, A-24 increased ß-endorphin levels in mouse brain. CONCLUSIONS AND IMPLICATIONS: A-24 induced its anti-hyperalgesic effect in rodents by directly blocking nociceptor PK(1) receptors and by activating the central opioid system and the descending pain control pathway through brain PK(2) receptors.

The new techniques of gynaecologic laparoscopy. Gasless, open Hasson, optic trocar.

BACKGROUND: New techniques of laparoscopy: gasless, open Hasson, optic trocars allow to avoid the risks of vessel and bowel injuries. The objective of this study was to evaluate the capability of a retractor system as an alternative to conventional technique without pneumoperitoneum and to assess if the system facilitates the use of conventional surgical instruments during gynaecological surgery. DESIGN: Prospective evaluation. SETTING: University-affiliated county hospital. PATIENTS: Gasless laparoscopy surgery was performed on 49 patients between December 1995 and July 1996 with a retractor system without pneumoperitoneum consisting of an intrabdominal retractor using conventional surgical and laparoscopic instruments and to enable a simultaneous vaginal approach. RESULTS: Gasless laparoscopy was successful in 44 (90%) of cases. A simultaneous vaginal approach was used in one third of indications including vaginal myomectomy and laparoscopic assisted hysterectomy. Conversion to laparotomy was required in 5% of cases. Mean procedure duration was 90 minutes and mean hospitalisation time was 5.7 days. CONCLUSIONS: The introduction of new techniques of laparoscopy: gasless, open Hasson, optic trocars has broadened the application of operative laparoscopy. Gasless technique in lieu of conventional laparoscopy can be performed reliably and safely for most gynaecological indications. The most outstanding benefit of this method is that it can be combined with a vaginal approach which is not possible using a pneumoperitoneum due to gas leakage. The place of gasless laparoscopy will depend on continuing development by instrument manufacturers, in order to achieve an instrument providing vision as good as that seen with the pneumoperitoneum.

[Celio-assisted vaginal surgery]. / La chirurgia vaginale celioassistita.

BACKGROUND: Remarkable progress has been made in laparoscopic surgery over the past few years. The evolution of laparoscopic techniques has enabled surgeons to undertake celio-assisted vaginal operations. In particular, the possibility of using mechanical retractors to lift the abdominal wall as an alternative to pneumoperitoneum now enables surgeons to operate simultaneously using a transvaginal and laparoscopic approach. Gas-free laparoscopy has introduced a new and very interesting concept of laparovaginal surgery. The uterus is in fact both an abdominal and pelvic organ and can therefore be reached more easily and with greater safety using a combined vaginal and laparoscopic technique. METHODS: A group of 17 patients underwent celio-assisted vaginal surgery. A prospective study was performed in patients with indications for vaginal operations who had given their informed consent to the use of this new surgical technique. Their mean age was 49.4 years. Mean parity was 1. RESULTS: Vaginal myomectomy was performed in 58.8% of cases, whereas 41.2% underwent vaginal hysterectomy. Laparoconversion was necessary in 17.6% of cases. Postoperative complications were rare (11.7%). The mean duration of surgery was 122.7 minutes. Mean hospital stay was 3.7 days. CONCLUSIONS: The considerable advantages of celio-assisted vaginal surgery using gas-free laparoscopy may be summed up as reduced operating time and reduced intra-abdominal pressure which significantly diminish the risk of thromboembolism. The disadvantages that were noted compared to pneumoperitoneum include: diminished lateral exposure of the abdominal cavity and paracholic grooves, reduced lifting of the rib margin and a greater presence of the intestinal ansae in the laparoscopic visual field in obese patients.

[Bacterial vaginosis. Prevention of recurrence]. / Vaginosi batterica. Profilassi delle ricorrenze.

Bacterial vaginosis (BV) is the main cause of vaginitis. The condition is characterised by an abundant and odorous vaginal loss, but more than half the patients with demonstrable signs of BV do not report symptoms at all. Gardnerella vaginalis (Gv) is often associated with BV, but it is not the sole factor responsible, as is shown by the fact that it can be isolated in the vagina of women withBV. In 1992 and 1993, 2630 patients, 1460 of them gynaecological and 1170 obstetric, were admitted to the Obstetrics and Gynaecology Clinic of Parma University. Amsel criteria were adopted for diagnosing BV. Cases of BV were treated with 5 mg/die 2% clindamycin vaginal cream for 7 days. In the event of recurrences, 250 mg tablets of metronidazol were added: 8 tablets in 4 administrations in a single day, treatment also being extended to the partner. Patients admitted in 1993 received a protocol of hygienic and behavioural standards, stress being laid on prophylaxisa measures even after the end of therapy. BV proved to be present in 12.3% of cases, of whom only half were symptomatic. The situation was practically stationary if the 2 years are considered separately. Recurrences of symptomatic bacterial vaginosis were 15% in the absence of protocol application and 8.3% after the protocol. Recurrences were less frequent in the asymptomatic forms. Compared to the total number od cases of BV, recurrences were significantly low (12.1% p < 0.001).

Methods of contraception and rates of genital infections.

Bacterial vaginosis, trichomoniasis and candidiasis are the most common genital infection. The aim of this study was to evaluate the various methods of contraception with regard to the prevalence of bacterial vaginosis and vulvo-vaginitis over a period of four years. We also evaluated in the same period the rates of trichomoniasis, candidiasis, bacterial vaginosis and vulvo-vaginitis between users and non users of contraceptional methods and the relationship between ages of patients and types of contraceptives. Finally we considered the change of contraceptive use with regard to age among two different periods. The IUD users showed a significant increase of B.V., T.v. and other bacteria and a decrease of the negatives compared to OC users. Barrier contraceptive users had a reduction (0.01 > p > 0.001) of B.V. and an increase (p < 0.001) of the negatives compared to IUD users. OC users had a significant (p < 0.05) increase in candidiasis, B.V. together with a reduction of the negatives compared to non users group. IUD users had a significant (p < 0.001) increase of B.V. and vulvo-vaginitis from other bacteria, and the reduction of the negatives. Teenagers use OC much more than adults, but less IUD (p < 0.001). The use of OC has increased and the use of IUD decreased among adults (p < 0.001). The barrier methods were seen to be statistically reduced.

PIP: During 1985-1986 and 1991-1992 in Italy, clinicians recruited 2387 patients attending the Centre for Sexually Transmitted Diseases (STDs) at the University of Parma with symptoms of genital infections. The study aimed to examine the various types of contraceptive methods in connection with the most common genital infections. Over the 4-year period, among patients with vulvo-vaginitis, IUD users had a higher rate than oral contraceptive (OC) users of bacterial vaginosis [BV] (24.9% vs. 15.7%; p 0.05), of trichomoniasis (1.7% vs. 1.3%), and of other infections (31.6% vs. 20%; p 0.05). They had a lower negative rate than OC users (23.9% vs. 43.4%; p 0.001). Patients using barrier methods (diaphragm and condom) had a lower rate of BV and a higher negative rate than IUD users (11.5% vs. 24.9%, p 0.01 and 49.6% vs. 23.9%, p 0.001, respectively). OC users had a higher rate of candidiasis and BV and a lower negative rate than the nonusers (19.6% vs. 14.8% and 15.7% vs. 11%; p 0.05 and 43.4% vs. 52.9%; p 0.001, respectively). IUD users had a higher rate of BV and vulvo-vaginitis from other bacteria and a lower negative rate than nonusers (24.9% vs. 11%, p 0.001; 31.6% vs. 20.4%, p 0.05; and 23.9% vs. 52.9%; p 0.001, respectively). Teenagers used OCs more often than did adults (29.3% vs. 15.6%) and were less likely to use the IUD (0.3% vs. 5.5) and no method (62.2% vs. 73.5%) (p 0.001). Between 1985-1986 and 1991-1992 among adults, OC use increased (9.9% vs. 17.9%; p 0.001) and IUD use and barrier method use decreased (8.9% vs. 4.1% and 9.3% vs. 3.9%, respectively; p 0.001).

[Vaginitis and vaginosis. Comparison of two periods]. / Vaginite e vaginosi. Due periodi a confronto.

Vaginitis is the most frequent gynecological disease. It is characterized by objective and subjective signs of inflammation and differs from bacterial vaginosis (BV) which is an abnormal condition of the vaginal ecosystem caused by the excessive growth of aerobic and anaerobic flora normally present in the vagina with an increased risk of pelvic inflammatory disease (PID). The authors report the results of a study carried out at the Centre for Gynecological Infections at the Clinic of Obstetrics and Gynecology of the University of Parma. 828 patients were enrolled in the study during the period 1985-86 and 1559 patients during the two-year period 1991-92. The aim of the study was to evaluate variations in epidemiological data for vaginitis and bacterial vaginosis in the two periods examined. No significant changes were observed (p > 0.05) with regard to the prevalence of Ca, Tv and BV forms. On the other hand, there was a significant reduction (p < 0.001) in the forms sustained by other microorganisms (above all, streptococcus and enterobacteria) between the first and second periods with a parallel increase in the number of negative cases. The analysis of the age distribution of vaginitis and BV showed a reduction of other microorganisms and an increase in negative vaginal swabs in adults (> 20 years old).

Perioperative prophylaxis in abdominal and vaginal hysterectomy.

The aim of this study is to evaluate the clinical efficiency of perioperative short-term prophylaxis in gynecological surgery, in order to prevent both systemic and local infections, caused either by aerobic or by anaerobic bacteria. A group of 320 patients, undergoing abdominal or vaginal hysterectomy and treated with perioperative antibiotic prophylaxis is compared, with 320 women undergoing conventional wide-spectrum antibiotic treatment from the first post-operative day for 4-5 days.

[Reconsideration and desire for tubal recanalization in women following voluntary sterilization]. / Pentimento e desiderio di ricanalizzazione tubarica dopo sterilizzazione volontaria nella donna.

PIP: More than 100 million people globally have resorted to voluntary sterilization to limit their fertility. Often negative psychological complications manifest themselves, such as depressive and remorseful feelings. The requests for tubal recanalization ranged from 1.3% to 15% according to the findings of 22 studies published between 1949 and 1969. The regret over the loss of fertility was higher among women with fewer than 4 children and among those who were sterilized after abortion. The maximum incidence of regret of 10-15% was reported in a 1959 study, and the lowest rates were reported in 1967 (1.3%) and in 1970 (2%). A review of 846 Puerto Rican women aged 15-49 years indicated a certain degree of regret in 21% and profound dissatisfaction in 11%, mainly because of young age and new partner. 25% of 497 subjects in a 1985 Montreal survey expressly requested the restoration of their fertility. Similar results were reported in a Danish study following up 547 cases of female sterilization during an observation period of 50 months. The international literature makes apparent that sterilization can be considered definitive mutilation in certain cases, which raises the question whether the woman who intends to undergo the operation possesses the intellectual, psychological, interpersonal, and social resources to make such a decision. Only absolutely freely chosen, voluntary sterilization can prevent consequences.^ieng

[Effectiveness of transdermal administration of 17-beta-estradiol in the management of menopause]. / Efficacia del 17-beta-estradiolo per via transdermica nel trattamento della menopausa.

Seventeen-beta-estradiol administered via a transdermic route was used to treat menopausal symptoms. The results obtained demonstrate the drug's good level of tolerability and considerable efficacy.

[Post-menopausal osteoporosis. A true and real social disease]. / L'osteoporosi post-menopausale. Una vera e propria malattia sociale.

The use of estrogens in menopausal women leads to a marked improvement in the quality of life, with the short-term disappearance of vasomotory phenomena and changes in psychomotive equilibrium. This therapy offers two long-term advantages: the prevention of osteoporosis and the cardiovascular diseases.

[Psychosexual implications of female sterilization]. / Problemi psicosessuali connessi alla sterilizzazione femminile.

PIP: According to data of the Italian Association for Demographic Education, from 1978 to 1991 a total of 16,000 sterilizations were carried out in patients with an average age of 36 years. There was an increasing frequency of anxiety, depression, and lack of satisfaction with sexual life, and deterioration of marital life as the consequence of the operations. Psychological improvement has been reported in only a few cases. Hysterectomy, mastectomy, abortion, and sterilization produce profound psychological effects in women. The ideal candidate for such intervention should be fully aware of the choice and be well informed about the reproductive system, and aged over 30 with at least 2 children in a stable marital relationship. A 1973 review of 80 different studies carried out in 12 different countries reported that 82% of women benefited from the operation. In a study of 180 patients in Glasgow, Scotland, psychosexual disorders were found, in only 3.6%. In a 1975 report, postoperative psychiatric disturbances in sexual life were recorded in 2% of 98 women. Another study of 94 women who were sterilized did not find any medical or psychological problems but did find patients who were completely satisfied 2 years later. In a study of 50 patients who underwent surgical sterilization by the Pomeroy technique during cesarean section, sexual behavior in the women, measured as desire, frequency of intercourse, and satisfaction, was unchanged in 47, while in 3 there were only modest variations in libido and frequency of intercourse. On the basis of these reports in the majority of cases the outcome of sterilization was favorable when assessing various gynecological problems over time. On the other hand, when the candidate is a young woman the information has to be particularly detailed and scrupulous with respect to risks and the probable irreversibility of sterilization.^ieng