Pain management during diagnostic office hysteroscopy in postmenopausal women: a randomized study.

Objective: This study aimed to compare efficacy and safety of lidocaine versus tramadol versus placebo in reducing the pain of diagnostic outpatient hysteroscopy (OH) in postmenopausal women.Materials and methods: This randomized double-blinded study included 156 menopausal women who received intrauterine lidocaine infusion or oral tramadol (50 mg) or placebo before diagnostic OH (52 women/group). Primary outcome was pain severity during the procedure using a 10-cm visual analog scale. Secondary outcomes were pain scores 10 and 30 min post procedure, satisfaction level, and ease of cervical entry.Results: Lidocaine had lower pain scores compared to placebo during and 10 min after the procedure (p < 0.001). Tramadol had lower pain scores than placebo during the procedure (p = 0.04), 10 min after the procedure (p = 0.03), and 30 min after the procedure (p = 0.04). Both lidocaine and tramadol resulted in an easier procedure than placebo (p < 0.001 and p = 0.04, respectively). Lidocaine had an easier cervical entry compared to tramadol (p = 0.004). Satisfaction scores in the lidocaine and tramadol groups were significantly higher than in the placebo group (p < 0.001).Conclusions: Lidocaine and tramadol were effective in reducing postmenopausal women-reported pain during and after diagnostic OH. However, lidocaine was better than tramadol in facilitating hysteroscope passage through the cervical canal and the reduction in pain levels with lidocaine was clinically relevant.Trial registration number: NCT03701984.

Genetic and environmental influences on non-specific neck pain in early adolescence: a classical twin study.

BACKGROUND: Prevalence of neck pain has increased among adolescents. The origins of adult chronic neck pain may lie in late childhood, but for early prevention, more information is needed about its aetiology. We investigated the relative roles of genetic and environmental factors in early adolescent neck pain with a classic twin study. METHODS: Frequency of neck pain was assessed with a validated pain questionnaire in a population-based sample of nearly 1800 pairs of 11-12-year-old Finnish twins. Twin pair similarity for neck pain was quantified by polychoric correlations, and variance components were estimated with biometric structural equation modelling. RESULTS: Prevalence of neck pain reported at least once monthly was 38% and at least once weekly 16%, with no significant differences between gender and zygosity. A greater polychoric correlation in liability to neck pain was found in monozygotic (0.67) than for dizygotic pairs (0.38), suggesting strong genetic influences. Model fitting indicated that 68% (95% confidence interval 62-74) of the variation in liability to neck pain could be attributed to genetic effects, with the remainder attributed to unshared environmental effects. No evidence for sex-specific genetic effects or for sex differences in the magnitude of genetic effects was found. CONCLUSIONS: Genetic and unique environmental factors seem to play the most important roles in liability to neck pain in early adolescence. Future research should be directed to identifying pathways for genetic influences on neck pain and in exploring effectiveness of interventions that target already identified environmental risk factors.

Contribution of nitric oxide to coronary vasodilation during hypercapnic acidosis.

The present study was performed to evaluate the role of nitric oxide (NO) in coronary vasodilation during hypercapnic acidosis (HC). The left anterior descending coronary arteries of 17 anesthetized, open-chest dogs were perfused with normal arterial blood or with arterial blood equilibrated in an extracorporeal circuit with 90% O2-10% CO2 [arterial carbon dioxide tension (PaCO2) 72 +/- 3 mmHg, arterial pH 7.16 +/- 0.02]. Coronary perfusion pressure (CPP) was initially set at 100 mmHg. Coronary blood flow (CBF) was measured with a Doppler transducer. Studies were conducted under constant-pressure (variable CBF; n = 13) and constant-flow (variable CPP) conditions (n = 4). Steady-state changes in CBF (or CPP) during HC and during intracoronary infusions of acetylcholine (ACh, 20 micrograms/min), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP, 80 micrograms/min), an endothelium-independent vasodilator, were compared before and after intracoronary infusion of a NO synthase inhibitor, either NG-nitro-L-arginine methyl ester (L-NAME, 4.5 mg) or NG-monomethyl-L-arginine (L-NMMA, 30 mg). Under constant pressure, L-NAME blunted increases in CBF by HC (274 +/- 32 vs. 113 +/- 24%) and ACh (400 +/- 43 vs. 68 +/- 17%), whereas increases in CBF by SNP were not significantly affected (207 +/- 34 vs. 186 +/- 18%). Results with L-NMMA were similar. Under constant flow, L-NAME attenuated decreases in CPP by HC and ACh, whereas it had no significant effect on decreases in CPP by SNP. In conclusion, HC elicits release of NO from coronary vascular endothelium via a direct effect rather than secondary to an increased flow rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of experimental schistosomiasis mansoni with praziquantel alone and combined with cimetidine.

In this work, praziquantel (EMBAY 8440, CAS 55268-74-1), an oral antihelminthic drug effective against the three species of schistosomes pathogenic to man, was tested alone and in combination with cimetidine (CAS 51481-61-9), aH2-receptor antagonist having a known potentiative power when combined with other drugs. Both drugs were tested in different doses and regimen either alone or in combination by giving them to S. mansoni infected Swiss albino mice (100 cercariae/mouse) 7 weeks post infection. Cimetidine was tested in doses of 50, 100 and 200 mg/kg for 2 consecutive days; praziquantel was given in doses of 100 and 500 mg/kg for 2 consecutive days. It was found that the best regimen was that of cimetidine and praziquantel when given simultaneously. Both drugs when given in a dose of 100 mg/kg for 2 consecutive days reduced the total worm load by 84.61%, while a percent reduction of 75.1% and 88.9% was recorded in hepatic and intestinal tissue egg load, respectively. Maximum efficacy was recorded when both drugs were given simultaneously at 200 mg/kg for 2 consecutive days. This regimen completely eradicated all schistosome worms and resulted in the maximum reduction in total tissue egg load (92%). The efficacy of this regimen was nearly the same as that of the full dose of praziquantel (500 mg/kg for 2 consecutive days), gave 100% worm eradication and 95% reduction in total tissue egg load.

Effect of praziquantel on the distribution of interstitial collagen types I and III and basement membrane collagen types IV and V in murine hepatic schistosomiasis.

The effect of specific chemotherapy (praziquantel) on liver function tests and on the distribution of collagen types I, III, IV and V was studied by indirect immunofluorescence in Swiss albino mice infected with Schistosoma mansoni. Treatment was started at 7 and 12 weeks after infection. Groups of treated and non-treated mice were killed 14 and 20 weeks after infection. Reduction in the amount of collagen and improvement of liver function were observed, especially when treatment was initiated early (7 weeks after infection), while collagen type III almost disappeared during the period of observation (13 weeks after treatment). The results indicate the importance of early specific treatment for schistosomiasis.

Schistosoma mansoni: angiotensin converting enzyme activity in mice under the influence of praziquantel and/or captopril.

Murine schistosomiasis is usually associated with hepatic granulomatous lesions together with high serum and granuloma angiotensin converting enzyme (ACE) activity. Praziquantel (PRZ) which is known to reduce granuloma size was studied to show whether this effect is related to changes in ACE activity. Furthermore, captopril was studied to show whether by inhibiting ACE activity, the drug could also affect granuloma size. PRZ, captopril, and their combination led to significant reduction in liver granuloma. However, in normal mice, captopril was shown to increase rather than decrease serum ACE. The decrease in ACE activity by PRZ was correlated with its curative effect in infected mice. However, in experimentally induced pulmonary granulomata, the drug reduced granuloma size without affecting ACE activity of either serum or granuloma. It may be concluded that reduction in ACE activity may be beneficial as far as diminution of granuloma size is concerned and irrespective of whether there is an active infection or not. The possible use of Captopril as an antihypertensive in bilharzial infections associated with hypertension would probably not adversely affect the granulomatous lesions.

Relationship between schistosomicidal drug efficacy, gonadal steroid hormonal changes and state of disease immunopathology in murine schistosomiasis mansoni.

The schistosomicidal efficacy of praziquantel (2 x 500 mg/kg), oxamniquine (1 x 100 mg/kg) and combined one-third the curative dose of each of them (333 mg/kg praziquantel + 33 mg/kg oxamniquine), were correlated to gonadal steroid hormonal changes and state of disease immunopathology, in mice infected with 100 Schistosoma mansoni (S. mansoni) cercariae. Maximum efficacy recorded with combination regimen particularly 4 weeks after treatment, was accompanied by maximum reduction in granuloma volume (65%), least fall in testosterone level (-56.2 and -60.2% in male and female mice respectively) and increased progesterone level (+33.9 and +81.5% in male and female mice respectively). These findings revealed a potentiated effect of combination therapy on mature infection and the possible involvement of gonadal steroid hormones in affecting the efficacy of schistosomicidal drugs and state of disease immunopathology.

Effect of schistosomiasis infection on the clearance of phenazone in mice.

The disposition phenazone (antipyrine) was used to study the effect of Schistosoma mansoni infection on the activity of drug metabolizing enzymes in mice. Plasma elimination rate constant (Ke), elimination half-life (t1/2e), clearance (CL) and apparent volume of distribution (Vd) were estimated 8 and 12 weeks after infection of mice with 80 S. mansoni cercariae. Liver and kidney function tests were performed simultaneously. Infection increased the levels of glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactic dehydrogenase (LDH), alkaline phosphatase (AP) and total proteins 8 and 12 weeks post infection. At the same time a decrease was recorded in the total cholesterol level. Moreover infection with S. mansoni produced a decrease in phenazone clearance with an increase in the area under the curve (AUC) of the drug 8 and 12 weeks post infection. Elimination half-lives were 57.92 +/- 14.10 and 72.72 +/- 4.14 min 8 and 12 weeks after infection, respectively, compared to 19.29 +/- 3.30 and 26.14 +/- 5.31 min in corresponding controls. No statistically significant change was recorded in the volume of distribution of phenazone in the groups studied. In addition no significant correlation was found between parameters of phenazone disposition and the enzyme levels studied 8 and 12 weeks after infection.

Comparative effect of tiaprofenic acid and piroxicam alone and as adjuvants to antibilharzial therapy on pulmonary granuloma in unsensitized mice.

Granulomata formed in the liver or lung of man and animals infected with schistosomiasis are common manifestation of an inflammatory delayed hypersensitivity reaction. Non-steroidal anti-inflammatory drugs (NSAIDs) (tiaprofenic acid and piroxicam) have been used alone and as adjuvants to praziquantel in treating pulmonary granulomata induced in mice by injecting them intravenously with S. mansoni eggs. The size of the granulomata, as well as some immunological parameters, have been measured at the end of treatment. Both anti-inflammatory drugs effectively reduced the size of lung granulomata in a dose-dependent manner. The immediate skin reaction and, to a lesser extent, the delayed reaction were reduced by these drugs. Tiaprofenic acid, but not piroxicam, reduced the percent macrophage migration inhibition in vitro. The combined therapy of either of the drugs with praziquantel did not result in an additive effect.

Study of some immunopharmacological properties of praziquantel in experimental schistosomiasis mansoni.

The immunopharmacological properties of praziquantel were studied in mice infected with Schistosoma mansoni. Hepatic granuloma measurement was the main parameter of assessment. Delayed foot pad swelling as an in vivo correlate for the delayed granulomatous hypersensitivity reaction was also determined. Fluorescent direct antigen-antibody reaction in the granuloma together with the immediate foot pad swelling were used to test for the humoral immune response. Praziquantel administered at seven weeks after infection in two dose regimens (3 X 250 mg kg-1 for three consecutive days and 3 X 83 mg kg-1 given four hourly within the same day was more or less equally effective in reducing the size of hepatic granuloma by 37-41% two weeks after treatment and by 81-85% one month after treatment. Delayed foot pad swelling using soluble egg antigen (SEA) was significantly suppressed one month after treatment by 53%. At nine weeks after infection the fluorescent antigen-antibody reaction in the granuloma was positive in the untreated controls, but at the same time (i.e. two weeks after treatment) it was negative in the praziquantel-treated mice. One month after treatment positivity was less compared to infected control mice. Reduction in worm burden, hepatic shift of the worms and the reduced number of ova per gram of tissue denoted the efficacy of the drug in its two dose regimens against the Egyptian strain of S. mansoni.

The immunological aspects of praziquantel in unsensitized mice with experimentally induced schistosome pulmonary granuloma.

The effects of praziquantel on cellular and humoral immune responses were studied in Swiss Albino mice and compared with the effects of potassium antimony tartrate. The experimental animals were antigenically primed by intravenous injection of Schistosoma mansoni eggs; the test drugs were given one day before egg injection and their effects monitored 16 days later. The size of the experimentally-induced pulmonary granulomata, immediate and delayed antigen-induced foot pad swelling, in vitro macrophage migration inhibition and the percentage of lymphocytes forming antibody and complement-dependent rosettes with erythrocytes (% EAC-R) were parameters used to assess the effect of the drugs. Praziquantel suppressed the size of pulmonary granulomata and the immediate and delayed foot pad reaction. Macrophage migration inhibition and the percentage of lymphocytes forming EAC-rosettes were not significantly affected. Tartar emetic was more effective as an immunosuppressant drug in these tests than praziquantel.

Effect of niridazole on the lipid pattern of the parasite and host tissues in experimental schistosomiasis mansoni.

THE LIPID pattern of blood and liver of mice infected with S. mansoni as well as in male and female worms was studied. Experiments were also carried out on non-infected and infected mice after treatment with Niridazole. It was found that Niridazole caused a significant increase in liver triglycerides and serum free acids. These changes were more pronounced in non-infected animals than in infected ones. The drug was found to reduce worm phospholipids and to increase their triglyceride level. The male worms were more affected than the female ones.