Assessment of levator hiatal area using 3D/4D transperineal ultrasound in women with deep infiltrating endometriosis and superficial dyspareunia treated with pelvic floor muscle physiotherapy: randomized controlled trial.

OBJECTIVES: Deep infiltrating endometriosis (DIE) is associated with chronic pelvic pain, dyspareunia and pelvic floor muscle hypertonia. The primary aim of this study was to evaluate the effect of pelvic floor physiotherapy (PFP) on the area of levator ani hiatus during Valsalva maneuver, assessed using transperineal ultrasound, in women with DIE suffering from superficial dyspareunia. METHODS: This was a randomized controlled trial of 34 nulliparous women diagnosed with DIE and associated superficial dyspareunia. After an initial clinical examination, all patients underwent three-dimensional/four-dimensional (3D/4D) transperineal ultrasound to measure the levator hiatal area (LHA) at rest, on maximum pelvic floor muscle contraction and on maximum Valsalva maneuver, and were asked to rate their pain symptoms using a numerical rating scale (NRS). Eligible women were assigned randomly (1:1 ratio) to no intervention (control group, 17 women) or treatment with five individual sessions of PFP (study group, 17 women). Four months after the first examination, all women underwent a second evaluation of pain symptoms and LHA on transperineal ultrasound. The primary outcome measure was the percentage change in LHA on maximum Valsalva maneuver between the baseline and follow-up examinations. The percentage changes in pain symptoms between the two examinations, including superficial and deep dyspareunia, dysmenorrhea, chronic pelvic pain, dysuria and dyschezia, were also evaluated. RESULTS: Thirty women, comprising 17 in the study group and 13 in the control group, completed the study and were included in the analysis. The percentage change in LHA on maximum Valsalva maneuver between the two examinations was higher in the study group than in the control group (20.0 ± 24.8% vs -0.5 ± 3.3%; P = 0.02), indicating better pelvic floor muscle relaxation. After PFP treatment, the NRS score for superficial dyspareunia remained almost unchanged in the control group (median change in NRS (Δ-NRS), 0 (interquartile range (IQR), 0-0)) while a marked reduction was observed in the study group (median Δ-NRS, -3 (IQR, -4 to -2); P < 0.01). Moreover, there was a significant difference between the PFP and control groups with regards to the change in chronic pelvic pain (median Δ-NRS, 0 (IQR, -2 to 0) vs 0 (IQR, 0-1); P = 0.01). CONCLUSIONS: In women with DIE, PFP seems to result in increased LHA on Valsalva maneuver, as observed by 3D/4D transperineal ultrasound, leading to improved superficial dyspareunia, chronic pelvic pain and pelvic floor muscle relaxation. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Diagnosis and treatment of uncommon ileal endometriosis: a case report and literature review.

Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. It is a common finding in premenopausal women and commonly affects the gastrointestinal tract, especially the rectosigmoid tract. Small bowel involvement is rare and usually asymptomatic making diagnosis difficult. Here we report an uncommon case of exophytic ileal endometriosis surgically treated. Detailed pre-operative counselling on the risk of ileal surgery should always be considered in all cases with endometriosis requiring surgery. We also present a review of the literature regarding the clinical presentation, diagnosis, and treatment of this challenging condition.

Time and space scattered volcanism of Mt. Etna driven by strike-slip tectonics.

High-resolution seismic reflection, magnetic and gravity data, acquired offshore of Etna volcano, provide a new insight to understanding the relationship between tectonics and spatial-temporal evolution of volcanism. The Timpe Plateau, a structural high pertaining to the Hyblean foreland domain, located offshore of southeastern Mt. Etna, is speckled by volcanics and strongly affected by strike-slip tectonics. Transpressive deformation produced a push-up and a remarkable shortening along WNW-ESE to NW-SE trending lineaments. Fault segments, bounding basinal areas, show evidence of positive tectonic inversion, suggesting a former transtensive phase. Transtensive tectonics favoured the emplacement of deep magmatic intrusive bodies and Plio-Quaternary scattered volcanics through releasing zones. The continuing of wrench tectonics along different shear zones led to the migration of transtensive regions in the Etna area and the positive inversion of the former ones, where new magma ascent was hampered. This process caused the shifting of volcanism firstly along the main WNW-ESE trending "Southern Etna Shear Zone", then towards the Valle del Bove and finally up to the present-day stratovolcano.

Lower plate serpentinite diapirism in the Calabrian Arc subduction complex.

Mantle-derived serpentinites have been detected at magma-poor rifted margins and above subduction zones, where they are usually produced by fluids released from the slab to the mantle wedge. Here we show evidence of a new class of serpentinite diapirs within the external subduction system of the Calabrian Arc, derived directly from the lower plate. Mantle serpentinites rise through lithospheric faults caused by incipient rifting and the collapse of the accretionary wedge. Mantle-derived diapirism is not linked directly to subduction processes. The serpentinites, formed probably during Mesozoic Tethyan rifting, were carried below the subduction system by plate convergence; lithospheric faults driving margin segmentation act as windows through which inherited serpentinites rise to the sub-seafloor. The discovery of deep-seated seismogenic features coupled with inherited lower plate serpentinite diapirs, provides constraints on mechanisms exposing altered products of mantle peridotite at the seafloor long time after their formation.

Spontaneous sister chromatid exchange and chromosome aberration frequency in humans: the familial effect.

The possible effects of environmental and genetic factors on spontaneous frequencies of sister chromatid exchanges (SCEs) and cells with chromosome aberrations (CAs) in human lymphocytes were investigated by analysing 177 completed families (mother, father and at least one child). After removing the effects of methodological, biological and life-style factors by the use of multifactor analysis of variance (MANOVA), SCEs and CAs residuals were analysed by simple correlation analysis and principal component analysis. SCEs and CAs inter-familiar variability was higher than that found within families. A significant correlation was found between the average SCE frequencies shared by parents (the so-called 'midpoint parents', or 'midparent') and offspring (linear slope b=0.26+/-0.07, p<0.05), but also between mother and father (b=0.23+/-0.11, p<0.05) suggesting the presence of an effective environmental factor. The midparent-offspring correlation was found to be sustained by the mother-offspring relationship (b=0.28+/-0.08, p<0.05), being the father-offspring correlation not significant (b=0.16+/-0.11, p0.05). Concerning CAs, no statistically significant correlation between parents was found, but the strong relationship between mother and offspring was confirmed (b=0.468+/-0.11, p<0.001). The SCEs correlation between mother vs. offspring disappeared for older offspring (over 23 years old). The obtained findings strongly showed that the genetic make-up is barely detectable in the presence of domestic environment factors which are shown to play the major role in determining the interfamilial variability of SCE and CA in a general population. These results strengthen the suitability of the use of SCEs and CAs analysis in human cytogenetic surveillance for the detection of effective environmental factors.

Pharmacokinetic variability and strategy for therapeutic drug monitoring of saquinavir (SQV) in HIV-1 infected individuals.

AIMS: To investigate the pharmacokinetic profile of the protease inhibitor saquinavir (SQV) after multiple doses in HIV-positive patients and to evaluate the possibility of predicting total body exposure of SQV from concentrations determined at single time points. METHODS: Twenty HIV-positive patients on steady-state treatment with SQV (Hard-Gel-Capsule, Invirase(R)) were enrolled in this study. Serial blood samples were obtained during a dosing interval. SQV plasma concentrations were determined by high performance liquid chromatography (h.p.l.c.) and pharmacokinetic parameters were determined by noncompartmental techniques. RESULTS: There was a marked interindividual variability in SQV pharmacokinetic parameters with a 11-fold variability in total systemic exposure to SQV, as expressed by AUC(0,8h) values (range: 268-3009 ng ml-1 h, CV: 69%). The oral clearance shows an interindividual CV of 75%. A strong correlation (r=0.94) was found between SQV plasma concentration at 3 h (C3 h ) and AUC(0,8h). CONCLUSIONS: This study shows that C3 h is a good predictor for total body exposure of SQV and might be useful to predict SQV disposition in HIV-positive patients on steady-state treatment.

Micronuclei assay and FISH analysis in human lymphocytes treated with six metal salts.

The capability of some metal compounds for inducing micronuclei (MN) in human lymphocytes was studied. In this investigation, Al (III), Cd (II), Hg (II), Sb (V), Te (VI), and Tl (I) salts were considered. The FISH (fluorescence in situ hybridization) technique with a centromeric probe was coupled with the MN assay in binucleated cells in order to detect both centromere-positive MN (C+ MN) due to malsegregation phenomena and centromere-negative MN (C- MN) due to chromosome breakage. The blood of two young nonsmoking male donors was employed for all experiments. In both donors, all the tested metal compounds, with the exception of Tl(2)SO(4), showed a statistically significant increase of MN compared to controls, at least at one dose. FISH analysis revealed an increase in the fraction of C+ MN for Al, Cd, and Hg compounds, and of C- MN for the Sb salt; however, this was not a statistically significant increase. A different efficiency was observed for the different metal compounds, in particular, KSbO(3) and CH(3)HgCl, which were highly genotoxic, whereas the others showed minimal effects.

[Bacterial pneumonia in HIV-infected patients] / Polmoniti batteriche in pazienti con infezione da HIV.

Patients and methods: This is a retrospective study performed on HIV-positive patients discharged from our Institution from January 1993 through December 1998 with a diagnosis of bacterial pneumonia. Cases of TB or atypical micobacterial infection were excluded from this analysis. Causative organisms were identified, when possible, by taking into account positive cultures from diverse sources (blood, sputum, pleural fluid and others). Results: In the 6-yr period we considered, 120 patients were identified. Among them, we were able to obtain clinical and imaging data on 98 cases. Focal infiltrates on chest X-ray studies were present in 87.7% of cases, 24.5% had a pleural effusion, 9.2% nodular lesions, 4.1% cavitary images and in 2 patients only hilar lymphadenopaties were noted. Causative agents resulted to be S. aureus (14 cases); P. aeruginosa (11); S. pneumoniae (6); R. equi (4); Enterobacter spp. and K. pneumoniae (3 cases each); E. coli, Peptostreptococcus spp and Enterococcus spp. (1 case each). No causative organism was isolated in 54 patients (55.1%) and the diagnosis was based on clinical and therapeutical grounds. Around half of cases (46.9%) responded well to therapy, while 11 (11.2%) died because of the lung infection. In 3 cases other opportunistic infections were the cause of death and 22 cases of relapse were recorded as well. Five patients resulted lost to follow-up. Conclusions: This retrospective study demonstrated a high prevalence of S. aureus lung infections along with the presence of otherwise rare causative organisms such as R. equi. Radiologic appearance of lung lesions did not differ substantially from the one of HIV negative patients. A relatively good response to antibiotic therapy was also noted.

Different effects of newly isolated saponins on the mutagenicity and cytotoxicity of the anticancer drugs mitomycin C and bleomycin in human lymphocytes.

Aim of the present paper was to assess by using the in vitro micronucleus (MN) test in human lymphocytes the effect of two plant extracts isolated from Blupeurum fruticosum (saponins) on the clastogenicity and cytotoxicity of the anticancer drugs mitomycin C (MMC) and bleomycin (BLM). One saponin showed a dose-dependent MMC-induced mutagenesis inhibition together with co-genotoxic effect on BLM-treated cultures. The remaining saponin did not significantly alter MN induction of both chemotherapeutic agents whereas it enhanced BLM cytotoxicity.

Sister chromatid exchange and micronucleus frequency in human lymphocytes of 1,650 subjects in an Italian population: I. Contribution of methodological factors.

The influence of several methodological factors on mean values of sister chromatid exchanges (SCEs) and micronuclei (MN) in peripheral lymphocytes of 1,650 subjects was analyzed. Donors belonged to a general healthy population living in Pisa and in two nearby small cities: Cascina and Navacchio (Ca-Na). Blood samples were collected over a period of 29 months and processed in three different laboratories of the some institute. Slides were analyzed by several scorers. Our data showed that lymphocyte proliferation indexes (PIs) and baseline mean values of SCEs were affected mainly by sampling period. This factor accounted for a percentage ranging from roughly 10% (Pisa) to 20% (Ca-Na) of total SCE variance and from roughly 10% (Pisa) to 13% (Ca-Na) of total PIs variance. A marginal effect was attributable to the different laboratories involved (maximum 3% for SCEs and 7% for PIs). The sampling period variable included many sources of variability such as culture media batches, fetal calf serum, PHA, BrdUrd, and seasonality. MN counts revealed a more marked dependence on processing laboratories. This factor accounted for a percentage of roughly 10% (Pisa and Ca-Na) of total variance, while the sampling period was marginally effective (about 1-4% of total variability). Because laboratories were equipped and supplied with the same materials and consumables and technicians were rotated constantly, the only variable ascertained was represented by the three different models of CO2 incubators used for lymphocyte culturing. When "month" and "incubator" variables were considered jointly, experimental variability accounted for 15-20% of total variance, both for PIs and mean values SCEs and MN. The variability due to slide scoring was reduced by assigning each slide to five different scorers and matching low with high scorers in each group. Present data show that when the study is performed under these controlled conditions, about 20% of total interdonor variability can be explained by experimental or seasonal factors.

Induction of aneuploidy by the antineoplastic drug estramustine in human lymphocytes.

Estramustine (EM) is an antineoplastic drug used in the therapy of human prostatic carcinoma. The aim of our work was to evaluate the potential aneuploidogenic activity of estramustine, by analysing its cytogenetic effects induced in human lymphocytes. To estimate the ability of EM to induce mitotic spindle disturbances, two parameters were used: the presence of c-mitoses (according to the degree of chromatid spreading and contraction) and mitotic index evaluation (increase after exposure indicating the accumulation of mitoses). EM induced c-mitoses and mitotic index increases starting from the 4 microM dose: statistically significant increases were observed up to the highest dose (40 microM). A strong correlation between c-mitoses and mitotic index increase was found. The micronucleus (MN) assay combined with the fluorescence in situ hybridization technique with a pancentromeric DNA probe was also carried out. Compared to the control, EM induced significant MN increases in binucleated lymphocytes at two doses (8-16 microM). Moreover, we found that estramustine induced significant percentages of MN with positive hybridization signal at the same doses, confirming the presence of entire chromosomes in micronuclei. Additional experiments included induction of numerical and structural chromosome aberrations, and evaluation of sister chromatid exchanges (SCE) and satellited (D- and G-group chromosomes) chromosome associations. The results of numerical chromosome aberration analysis indicated that EM was positive in inducing a statistically significant increase in aneuploid cells and/or polyploid cells at all doses tested. On the basis of these observations, EM may be defined as a typical aneuploidy inducer, whereas it was not found to increase the frequency of structural chromosome aberrations and SCE frequency.

Comprehensive investigation of the presence of JC virus in AIDS patients with and without progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML), a viral-induced demyelinating disease, is becoming relatively common, while many diagnostic and pathogenetic aspects remain to be clarified. A study was therefore undertaken in 64 AIDS patients suffering from various neurological disorders, including PML (12 subjects), with the specific objective of searching for JC virus (JCV) DNA by nested PCR (n-PCR) in cerebrospinal fluid (CSF), peripheral blood mononuclear cells (PBMCs), and urine collected from all patients. CSF examination, CD4 and CD8 counts, neurological examinations, and neuroradiological investigations were undertaken. JCV DNA was detected in 92% of CSF specimens in 75% of the PBMCs and urine samples from the PML patients, whereas among the non-PML patients JCV DNA was not detected in any CSF samples, but was found in 10% of PBMCs and in 39% of the urine specimens. BKV and JCV DNA viruria was observed simultaneously in 6% of the AIDS patients without PML. The routine CSF tests including IgG oligoclonal bands, the Link, and Tourtellotte IgG indexes, did not show a typical pattern in PML cases. The data obtained clearly indicate that the detection of JCV DNA in CSF constitutes an efficient marker for PML diagnosis. The simultaneous presence of JCV DNA in the CSF, PBMCs, and urine samples from the PML patients, who did not differ from controls with regard to their immunosuppressive status, suggests that JCV could be carried into the central nervous system (CNS) by infected PBMCs.

[Clinical significance of diplopia in HIV infection. Assessment of a personal caseload and review of the literature]. / Significato clinico della diplopia in corso di infezione da HIV. Valutazione di una casistica personale e analisi della letteratura.

Diplopia is one of the neuro-ophthalmic manifestations that can be observed during HIV-infection. The etiologic agents of diplopia in HIV-positive patients can be identified with HIV itself or opportunistic pathogens or other related conditions. We reviewed the clinical records of 13 HIV-positive patients with mono or bilateral diplopia, focusing on etiologic agents, clinical evaluation and prognosis. This review encompassed all cases observed from January 1992 to June 1995 at the Infectious Diseases Department, Policlinico S. Matteo, University of Pavia. All patients underwent a complete ophthalmologic examination, including visual acuity, anterior segment evaluation with biomicroscopy, dilated indirect ophthalmoscopy and ocular motility evaluation (with Cover test and Hess-Lancaster test). If requested by clinical findings, radiologic (TC and/or MRI) and cerebrospinal fluid examination were performed in some patients. The most common causes of diplopia-CNS lesions or ocular diseases-, resulted in agreement with those reported in the literature (T. gondii, C. neoformans, non-Hodgkin lymphomas, HIV, JC virus, CMV). We were able to confirm, according to our experience, that diplopia occurrence is often a negative prognostic factor, since it is commonly associated with CNS conditions. In most cases diplopia can herald a near demise (8 patients on 13 died with 60 days from diplopia onset). In those cases where a treatment was available (2 cases of cryptococcosis, 1 case of neurotoxoplasmosis and 1 case of CMV retinitis) a complete resolution of neuro-ophthalmic symptoms was achieved.

[Role of clinical pharmacology in the monitoring of therapy of HIV-infected subjects]. / Ruolo della farmacologia clinica nel monitoraggio della terapia in soggetti con infezione da HIV.

The number of subjects with HIV infection or full-blown Acquired Immunodeficiency Syndrome (AIDS) is increasing throughout the world and the range of related opportunistic conditions (infections, neoplasms or degenerative disorders) is also increasing. Consequently, AIDS patients are likely to be prescribed a great number of different drugs. HIV infection is a progressive phenomenon, characterized by inevitable and often irreversible changes which may influence drug disposition, enhancing the risk of toxic adverse effects and drug interactions. One of the stages for the development of new agents and the establishment of an effective therapy is to conduct pharmacokinetic studies. Even though such studies are difficult to realize in AIDS subjects, the knowledge of altered pharmacokinetics of a drug in disease states offers an unique approach for improving and perhaps optimizing the therapeutic management. The purpose of this article is to review our current understanding of how HIV infection influences the various processes of drug disposition (i.e. absorption, distribution, metabolism and excretion).

Detection of the centromere in micronuclei by fluorescence in situ hybridization: its application to the human lymphocyte micronucleus assay after treatment with four suspected aneugens.

The human lymphocyte micronucleus (MN) test combined with fluorescence in situ hybridization (FISH) of a centromeric probe is considered a useful screening assay to distinguish between clastogenic and aneugenic agents. Four suspected aneuploidy-inducing chemicals, acetaldehyde (AA), diethylstilbestrol (DES), diethylstilbestrol dipropionate (DESdp) and griseofulvin (GF), have been evaluated with the assay. All compounds induced a significant increase of MN at all doses tested. After the application of the FISH technique with a pancentromeric DNA sequence, DES, DESdp and GF showed a statistically significant increase in the percentage of positive signals compared with the control culture. GF induced the highest percentage of centromere-positive MN observed to date (>90% on average). AA did not show a significant difference in the percentage of centromere-positive MN. The results indicate that in human lymphocytes DES, DESdp and GF act primarily as aneugens, while AA seems capable of causing both chromosome breakage and aneuploidy.

Monitoring human exposure to urban air pollutants.

A multidisciplinary study on a general population exposed to vehicle exhaust was undertaken in Pisa in 1991. Environmental factors such as air pollution and those associated with lifestyle were studied. Meanwhile, biological and medical indicators of health condition were investigated. Chromosomal aberrations, sister chromatid exchanges (SCEs), and micronuclei in lymphocytes were included for the assessment of the genotoxic risk. Because of the large number (3800) of subjects being investigated, standardization of protocols was compulsory. The results on data reproducibility are reported. To assess the reliability of the protocol on a large scale, the population of Porto Tolle, a village located in northeast Italy, was studied and compared to a subset of the Pisa population. Preliminary results showed that probable differences between the two populations and individuals were present in terms of SCE frequencies. The study was potentially able to detect the effects of several factors such as age, smoking, genetics, and environment. The in vitro treatment of lymphocytes with diepoxybutane confirmed the presence of more responsive individuals and permitted us to investigate the genetic predisposition to genetic damage. The possible influence of environmental factors was studied by correlation analyses with external exposure to air pollutants as well as with several lifestyle factors.