Abnormal uterine bleeding: medical treatment with vaginal danazol and five-year follow-up

STUDY OBJECTIVE: To evaluate the clinical efficacy and patient satisfaction of long-term danazol delivered vaginally as treatment for heavy menstrual bleeding. DESIGN: Prospective study (Canadian Task Force classification II-3). SETTING: University hospital. PATIENTS: Twenty premenopausal women with endometrial hyperplasia or endometrial polyps. INTERVENTION: After curettage or hysteroscopic-directed biopsies, women used one 200-mg tablet of danazol vaginally every day, continuing the therapy as long as they were totally satisfied with it. MEASUREMENTS AND MAIN RESULTS: Women were instructed to keep a diary of menstrual bleeding and to rate blood loss on a visual analog scale from zero (no blood loss) to 10 (gushing-type bleeding). They were seen every month for 3 months, then every 3 months for 9 months, and then every 6 months for 4 years for Papanicolau smear, pelvic examination, and transvaginal ultrasonography. They were asked to bring their diary of menstrual bleeding. They were asked about side effects and their satisfaction with the therapy. Peripheral blood was drawn for blood count and serum chemistries. Hysteroscopic-directed biopsies were repeated after 3 months of therapy in women with endometrial hyperplasia. The severity of blood loss was significantly reduced in all women after 3 months of treatment. All women with endometrial hyperplasia had regression of hyperplastic endometrium. None of the women with endometrial polyps had sonographic signs of recurrence during therapy. Only 10 women (50%) completed 1-year follow-up, and only 5 women (25%) completed 5-year follow-up. CONCLUSION: These results suggest that long-term administration of vaginal danazol after curettage or hysteroscopic-directed biopsy is both efficacious and safe in women with heavy menstrual bleeding, but the rate of discontinuance is high.     

Ischemic-type biliary lesions in liver transplant recipients: evaluation with magnetic resonance cholangiography

We assessed the diagnostic value of magnetic resonance cholangiography (MRC) when evaluating ischemic-type biliary lesions in the follow-up of liver transplant patients. We retrospectively reviewed magnetic resonance imaging and MRC of 28 liver transplant recipients with ischemic changes of the biliary tree. The MR examinations were performed at 1.5 T. After the acquisition of axial T1w and T2w sequences, MRC involved a coronal respiratory-triggered, fat-suppressed, two-dimensional, thin-slab, heavily T2w fast spin-echo sequence, and/or a coronal breath-hold, thin- and thick-slab, single-shot T2w sequence. Eleven patients underwent either surgical reconstruction of the biliary system (n = 4) or liver retransplantation (n = 7); the pathologic specimens were employed as standard of reference. The final diagnosis was obtained through direct cholangiography in the remaining cases. Without knowledge of the surgical, pathologic, and cholangiographic findings, two experienced investigators evaluated in conference the MR images to determine the presence of biliary tract abnormalities. MRC demonstrated strictures involving the hepatic bifurcation and the extrahepatic bile duct of the graft in 26 patients; a concomitant thickening of the biliary wall was described in 18 out of these 26 subjects. MRC also showed sludge or stones formation in the donor common bile duct in 16 out of these patients. In conclusion, MRC allows noninvasive, reliable, assessment of ischemic-type biliary lesions in liver transplant recipients.     

Electroneurography index based on nerve conduction study data: method and findings in control subjects

We developed a summary score of data obtained from nerve conduction studies (NCS). The principle of such approach is that when a nonrandom trend to lower amplitudes or conduction velocities is present, it may be revealed by a summary nerve conduction score. In a group of normal subjects, peroneal, sural, ulnar, and superficial radial nerves were studied; age- and height-related F-wave and soleus H-reflex latencies were also examined. Z-scores of distal latencies, amplitudes, conduction velocities, F-wave latencies, and H-index were averaged in order to obtain three electroneurography (ENG) indices: a simple arithmetic (ENG index 1) and two weighted means (index 2 and index 3), assigning a double or triple weight to lower limb z-scores. Reference limits were established using multiple regression equations of ENG indices against age and height. This technique could be useful in providing a better cut-off between normal and diseased populations and in improving test-retest variability of NCS when follow-up studies are required.     

Sleep-related hyperkinetic seizures of temporal lobe origin

Sleep-related hyperkinetic seizures are a common feature of nocturnal frontal lobe epilepsy. Although sleep-related seizures with a temporal lobe origin have been reported, they commonly lack hyperkinetic activity. The authors describe three patients with sleep-related seizures characterized by frenetic, agitated, hyperactive movements (bimanual/bipedal activity, rocking, axial, pelvic, and hemiballistic movements), in whom stereo-EEG investigation and surgical outcome demonstrated a temporal lobe origin of the attacks.     

Bilateral laparoscopic transperitoneal ligation of ovarian veins for treatment of pelvic congestion syndrome

STUDY OBJECTIVE: To evaluate the efficacy and safety of bilateral laparoscopic transperitoneal ligation of the ovarian veins in women with symptomatic pelvic varices. DESIGN: Prospective pilot study performed in a small series (Canadian Task Force classification III). SETTING: Urban hospital in Turin and University hospital in Cagliari, Italy. PATIENTS: Twenty-three women. INTERVENTION: Bilateral laparoscopic transperitoneal ligation of the ovarian veins. The right ovarian vein was reached by incising posterior peritoneum below the mesentericoparietal fossa in all women. The left ovarian vein was reached by reflecting medially the left colon in 10 women and by incising the posterior peritoneum covering the aorta 2 cm below the inferior duodenal fold in 13. MEASUREMENTS AND MAIN RESULTS: After the plateau of the learning curve was reached, average operating time was about 60 minutes without complications. Complete remission of pain and absence of pelvic varicosities lasted for 12 months. CONCLUSION: The laparoscopic transperitoneal paraaortic approach to bilateral ligation of ovarian veins near their origin could be a new treatment option for pelvic congestion syndrome.     

Mutation analysis of candidate genes in melanoma-prone families: evidence of different pathogenetic mechanisms at chromosome 9P21

Putative tumour suppressor genes CDKN2A and CDKN2B (on chromosome 9p21) and CDKN2A-interacting cell growth regulatory genes CDK4 and Id-1 have been demonstrated to be involved in the pathogenesis of malignant melanoma (MM). Mutation analysis of these candidate genes was performed in MM families from southern Italy with three or more affected members or two affected members and one or more relative with histologically diagnosed atypical naevus. Two CDKN2A mutations, Arg24Pro and 1-292 G>A, were observed in two (15%) families; except for CDKN2A and Id-1 polymorphisms, no sequence variations were detected in the remaining genes. Screening among 119 sporadic MM cases revealed two additional CDKN2A mutations at very low prevalences. Identification of a large shared haplotype at 9p21 in some MM families negative for CDKN germline mutations suggests that other CDKN-inactivating mechanisms may be responsible for MM predisposition or, alternatively, additional susceptibility gene(s) may be present on chromosome 9p21. Fluorescence in situ hybridization analysis of a subset of MM tissue sections seemed to indicate that the D9S171 locus may be involved in MM pathogenesis.     

Dopamine D1 receptor agonists induce penile erections in rats

The dopamine receptor agonist apomorphine has been recently introduced in the treatment of erectile dysfunction. While it is well established that dopamine D2-like receptors play a crucial role in this effect, conflicting result are reported in the literature as for the role of dopamine D1-like receptors. The aim of this study was to determine the effect of systemic administration of dopamine D1-like receptor agonists on penile erection in rats. Male Wistar rats were treated with three different, and not structurally related, dopamine D1-like receptor agonists: the partial agonists SKF38393 ((+) 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine) and CY 208-243 ((-)-4,6,6a,7,8,12b-exahydro-7-methylindole [4,3-ab]fenantridine), and the full agonist A 77636 ((-)-(1R,3S)-3-Adamantyl-1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1H-2-benzopyran hydrochloride). All three compounds dose-dependently increased the number of penile erections, with the full agonist A77636 showing a more pronounced effect with respect to the other two. Moreover, the dopamine D1-like receptor antagonist SCH 23390 ((R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) dose-dependently antagonised A77636 effect. These results show that systemic administration of dopamine D1-like receptor agonists induce penile erection in rats. This observation suggests that dopamine D1-like receptor agonists might be considered as a possible alternative to apomorphine in the treatment of erectile dysfunction, thus avoiding the typical side effects related to the stimulation of dopamine D2-like receptors such as nausea.     

Cannabinoid mechanism in reinstatement of heroin-seeking after a long period of abstinence in rats

Because opioid and cannabinoid systems have been reported to interact in the modulation of addictive behaviour, this study was aimed at investigating the ability of cannabinoid agents to reinstate or prevent heroin-seeking behaviour after a prolonged period of extinction. In rats previously trained to self-administer heroin intravenously, non-contingent non-reinforced priming administrations of heroin and cannabinoids were presented after long-term extinction, and lever pressing following injections was observed. Results showed that: (i) intravenous priming infusions of heroin (0.1 and 0.2 mg/kg) lead to reinstatement of drug-seeking behaviour; (ii) intraperitoneal priming injections of the central cannabinoid receptor agonists R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2,3-de]-1,4-benzoxazinyl) (1-naphthalenyl)methanonemesylate (WIN 55,212-2, 0.15 and 0.3 mg/kg) and (-)-cis-3-[2-hydroxy-4(1,1-dimethyl-heptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol (CP 55,940, 0.05 and 0.1 mg/kg), but not delta9-tetrahydrocannabinol (delta9-THC, 0.1-1.0 mg/kg), effectively restored heroin-seeking behaviour; (iii) intraperitoneal priming injection of the central cannabinoid receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)4-methyl-1H-pyrazole-3-carboxamide (SR 141716A, 0.3 mg/kg) did not reinstate responding, but (iv) completely prevented heroin-induced reinstatement of drug-seeking behaviour. Moreover, heroin-seeking behaviour was still present for a few days following cannabinoid primings, indicating a long-lasting effect of cannabinoids on responding for heroin. These findings indicate that relapse to heroin after an extended drug-free period is triggered by cannabinoid agonists and that SR 141716A prevents drug-seeking behaviour, suggesting that the use of the cannabinoid antagonist could have some therapeutic benefits in heroin-induced relapse.