[Modalities of gynecological follow-up of transgender patients - Literature review]. / Modalités du suivi gynécologique chez les patients transgenres ­ Revue de littérature.

Transgender patients are at increased risk of cancer, sexually transmitted diseases, short- and long-term postoperative complications in patients with vaginoplasty, but also unwanted pregnancy in non-hysterectomized trans men. However, access to care is often difficult for these patients, who often do not benefit from appropriate gynecological monitoring, especially for fear of judgment or discrimination. In view of the health risks of these patients, it is essential to be able to offer them specific and adapted gynecological follow-up. To date, there are no clear recommendations regarding the gynecological follow-up of transgender patients. We relied on the recommendations of the World Professional Association of Transgender Health (W-PATH) and the Endocrine Society Guideline and performed a literature review. We carried out several searches via pubmed in order to explore one by one the different aspects of gynecological follow-up, in particular of non-hysterectomized transgender men and transgender women with a vaginoplasty. It emerges from this a lack of follow-up of transgender people, with a reluctance to consult a gynecologist, associated with the lack of knowledge and experience of health professionals. Due to the risks identical to those of the general population, added to those specific to transgender people, it is important to be able to offer these patients specialized and personalized gynecological follow-up, and to raise awareness and train health professionals on the importance of and the specificities of the gynecological follow-up of these patients.

Pitfalls and challenges associated with phenoconversion in forensic toxcicology.

PURPOSE: In recent years, several publications have demonstrated the interest and the usefulness of pharmacogenetics in forensic toxicology. However, this approach remains namely focused on DNA-based phenotype, which may potentially lead to misinterpretation. Other determinants such as co-medication or physiological parameters may also impact the phenotype. This article aims to highlight the importance of considering such determinants in forensic toxicology, through the original case of a heroin-related fatality. METHOD: Ethanol concentration determination and toxicological screening were performed using gas chromatography with flame ionization detection, liquid chromatography with diode array detection and gas chromatography with mass spectrometry detection. CYP2C19 and CYP2D6 genotypes were determined by Taqman® real-time PCR analyses. RESULTS: Femoral blood analyses revealed the presence of ethanol, morphine, codeine, venlafaxine (VEN), O-desmethylvenlafaxine (ODV) and N-desmethylvenlafaxine (NDV), paroxetine, and risperidone. 6-acetylmorphine was also identified in urine. VEN, paroxetine and risperidone were quantified at supra-therapeutic or toxic blood concentrations. NDV was not quantified. The metabolic ratio of VEN (ODV to VEN) was exceptionally low (about 0.7). Pharmacogenetics testing showed that the patient was heterozygous for the CYP2C19*2 loss-of-function allele, which predict an intermediate metabolism for CYP2C19. None of the deficient CYP2D6 alleles investigated were identified. Those results suggest an extensive CYP2D6-metabolism phenotype. CONCLUSION: A discrepancy was seen between the results of the genomic evaluation and the observed metabolic ratio of VEN. This tends to exclude a genetic origin and lead us to formulate other hypotheses, such as phenoconversion that may have been induced by drug interaction involving patients' regular medications. Phenoconversion is as a complex phenomenon that leads to genotype-phenotype mismatch without any genetic abnormality particularly described for cytochromes P450 2D6 and 2C19. Although transient, phenoconversion can have a significant impact on the analysis and interpretation of genotype-focused clinical outcomes correlation and in forensic toxicology conclusions.

Baclofen overdose following recreational use in adolescents and young adults: A case report and review of the literature.

Over the past twenty years, psychotropic drug abuse by young people, especially by teenagers, has received special attention. Here, we present the case of baclofen overdose in a 16-year-old male who recreationally, and probably recurrently, self-administered baclofen. In addition, a review of other cases was conducted. The 16-year-old boy presented to emergency department with digestive signs followed by agitated confusion. Detection and determination of baclofen concentration were achieved using liquid chromatography tandem mass spectrometry. Baclofen was detected in plasma and urine, at 420 ng/mL and 64 900 ng/mL respectively. Further, an English exhaustive literature search was performed using several different scientific databases without any limiting period in order to identify scientific articles dealing with baclofen overdose following a recreational use among adolescent and young adults. Five publications describing baclofen overdoses following a recreational use among adolescents and young adults have been published reporting19 cases, all involving a non-fatal overdose, with baclofen concentrations ranging from less than 20-1322 ng/mL. Baclofen is a psychotropic drug and its recreational use among adolescents and young adults represent a serious problem and should be considered by healthcare professionals. Among young people, baclofen poisoning remains relatively infrequent or most likely underestimated and these observations highlight the importance of constructive communication and joining efforts of clinicians and analytical toxicologists.

[Endovascular renal nerve ablation as a treatment for resistant hypertension]. / La dénervation rénale endovasculaire dans le traitement de l'hypertension artérielle résistante.

Radiofrequency-induced renal ablation is a non-pharmacologic therapeutic approach for the treatment of essential resistant hypertension, with a stable blood pressure lowering effect. However, data from published studies cannot conclude yet on the long-term efficacy and safety of the procedure. Therefore, the various techniques of renal nerve ablation (radiofrequency, cryoablation, ultrasounds) need further evaluation in clinical research trials. According to recent national and international recommendations, renal ablation should be reserved for patients with essential resistant hypertension.

The p400/Tip60 ratio is critical for colorectal cancer cell proliferation through DNA damage response pathways.

The Tip60 histone acetyltransferase belongs to a multimolecular complex that contains many chromatin remodeling enzymes including the ATPase p400, a protein involved in nucleosomal incorporation of specific histone variants and that can directly or indirectly repress some Tip60-dependent pathways. Tip60 activity is critical for the cellular response to DNA damage and is affected during cancer progression. Here, we found that the ratio between Tip60 and p400 mRNAs is affected in most colorectal carcinoma. Strikingly, reversing the p400/Tip60 imbalance by Tip60 overexpression or the use of siRNAs resulted in increased apoptosis and decreased proliferation of colon-cancer-derived cells, suggesting that this ratio defect is important for cancer progression. Furthermore, we demonstrate that the p400/Tip60 ratio controls the oncogene-induced DNA damage response, a known anticancer barrier. Finally, we found that it is also critical for the response to 5-fluorouracil, a first-line treatment against colon cancer. Together, our data indicate that the p400/Tip60 ratio is critical for colon cancer cells proliferation and response to therapeutic drugs through the control of stress-response pathways.

Arterial stiffness and enlargement in mild-to-moderate chronic kidney disease.

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular morbidity and mortality. Arterial stiffness and remodeling have been well documented in patients with end-stage renal disease, but little is known about arterial phenotype in CKD patients with moderate reduction in glomerular filtration rate (GFR). In total, 95 patients (58+/-15 years, mean+/-s.d.) with CKD and GFR measured by renal clearance of (51)Cr-ethylenediaminetetraacetate were compared to 121 hypertensive patients without CKD (59+/-11 years), and 57 normotensive subjects (56+/-6 years). Common carotid artery diameter, intima-media thickness (IMT), distensibility, and Young's elastic modulus were noninvasively determined with a high-definition echotracking system. Patients with CKD had a significantly larger carotid internal diameter than in hypertensives and normotensives (6.32+/-1.05, 5.84+/-0.74, and 5.50+/-0.64 m x 10(-3), respectively; P<0.001), resulting in 25% and 11% increases in circumferential wall stress, respectively, since no significant difference in IMT was observed. Carotid distensibility and elastic modulus did not significantly differ between CKD and hypertensives; normotensives had significantly higher distensibility and lower elastic modulus than CKD and hypertensive patients. Carotid-femoral pulse wave velocity was significantly higher in CKD patients than in hypertensives and normotensives. In multivariate analyses either involving the entire population or restricted to CKD patients, GFR was independently and strongly related to carotid diameter and elastic modulus. Arterial enlargement and increased arterial stiffness occur in parallel with the decline in renal function in patients with mild-to-moderate CKD.

Symptom perception: psychological correlates of symptom reporting and illness behavior of women with medically unexplained gynecological symptoms.

Medically unexplained (gynecological) symptoms can be viewed as an indication of the somatization of negative emotions. Most studies regarding psychological correlates of medically unexplained gynecological symptoms have paid attention only to certain personality characteristics of women with these symptoms. In this study the reporting of physical symptoms and the resulting illness behavior is explained in terms of information processing or a perception process, i.e. the process by which people detect and interpret physical sensations as symptoms of illness (symptom perception). Symptom perception is in part determined by environmental characteristics and cognitive and emotional processes, such as variation in daily life, (coping with) emotional threat and the use of cognitive illness schemes. Differences in symptom perception and illness behavior of women with medically unexplained and explained gynecological symptoms, compared to women with medically explained gynecological symptoms and a control group, were established with the help of a questionnaire, containing a number of scales. As expected, women with medically unexplained gynecological symptoms had higher reports of common symptoms and sensations and showed also more other illness behavior than the other two groups. They reported less variation and more threat in daily life than the other two groups. These variables together with the use of illness schemes contributed most to symptom reporting of women with medically unexplained symptoms. It is concluded that defence against threat is probably an important determinant. Suggestions for further research and some practical implications are discussed.

Detection of human papillomavirus types by the polymerase chain reaction and the differentiation between high-risk and low-risk cervical lesions.

By means of a consensus polymerase chain reaction (PCR) method, the prevalence of HPV types was determined in cervical biopsies from 137 women referred to the gynecological outpatient clinic for colposcopy because of an abnormal cervical smear. The prevalence of HPV was 80.3%. There was a statistically highly significant rise in the prevalence of the oncogenic HPV types (16, 18, 31, 33) with increasing severity of cervical intraepithelial neoplasia (CIN I to III), indicating a role for these HPV types in the pathogenesis of cervical cancer. The prevalence of other HPV types decreased significantly with the severity of the lesion, suggesting that these HPV types play a less significant role in this process. These data indicate that HPV typing with PCR may be a valuable tool for distinguishing between high-risk and low-risk cervical lesions. Furthermore, our results suggest that the detection of HPV types by consensus PCR in the cervix of patients with an abnormal smear but without histologically detectable CIN is a useful tool for predicting which of these patients will eventually develop CIN. Finally, a relatively low percentage (3%) of HPV double infections is reported in this study.

Human papillomavirus type 16 transcripts expressed from viral-cellular junctions and full-length viral copies in CaSki cells and in a cervical carcinoma.

We have mapped using the RNA PCR the viral-cellular junctions of HPV16 viral-cellular cotranscripts expressed in CaSki cells and a cervical carcinoma to nt 3728 and 881, respectively. Both junctions were located within the E1-E2 region. Examination of the cellular sequences of the cotranscripts showed the presence of a polyadenylation signal in each of the transcripts. In CaSki cells and in the cervical carcinoma transcripts derived from the full-length early region including the E2 transcript were also detected. Our results suggest that the utilization of a cellular polyadenylation site could be important in the development of cancer by HPV.

Uniformity of the splicing pattern of the E6/E7 transcripts in human papillomavirus type 16-transformed human fibroblasts, human cervical premalignant lesions and carcinomas.

We utilized the RNA polymerase chain reaction (PCR) to analyse the transcripts of the E6/E7 open reading frames of human papillomavirus type 16 (HPV-16). Total RNA was isolated from 14 cervical squamous carcinomas, nine cervical intraepithelial neoplasias and from human fibroblasts transformed with different HPV-16 constructs. In all specimens two spliced transcripts were detected. Sequence analysis of the cloned PCR products showed that both transcripts were generated by splicing out an intron in E6, from nucleotides (nt) 226 to 409 in one transcript and from nt 226 to 526 in the other. The major transcript present in all RNA specimens had the smallest intron in E6. The RNA PCR described here is the method of choice for analysing splice and donor sites in tissue specimens where a limited amount of RNA is available. Results obtained with transformed cells revealed no difference in splicing whether HPV-16 was controlled by its homologous promoter or by a heterologous promoter, the Rous sarcoma virus long terminal repeat.

Localization of human papillomavirus type 16 DNA using the polymerase chain reaction in the cervix uteri of women with cervical intraepithelial neoplasia.

The localization of human papillomavirus type 16 (HPV-16) DNA throughout the cervix uteri of women with cervical intraepithelial neoplasia (CIN) was studied by utilizing the polymerase chain reaction technique directly on histologically defined sections of paraffin-embedded cervical tissue obtained by conizations. HPV-16 DNA was detected only in the sections that contained CIN lesions and/or koilocytes. No HPV-16 DNA was detected in sections that contained only normal epithelium. This is in accordance with HPV-16 playing a role in the development of CIN lesions.

Evaluation of different DNA-DNA hybridisation techniques in detection of HPV 16 DNA in cervical smears and biopsies.

The sensitivities of dot blot hybridisation and in situ filter hybridisation for the detection of HPV DNA were compared. Dot blot hybridisation was 10-50 times more sensitive than in situ filter hybridisation in detecting HPV 16 DNA in the cervical cancer cell lines SiHa and CaSki. Cervical smears collected from 51 women with a history of one or more abnormal cervical smears were tested by both hybridisation techniques for the presence of HPV 16 DNA; 11 were positive in the in situ filter hybridisation, 35 in the dot blot hybridisation. Thirty-five cervical biopsies available from this group of 51 women were processed for dot blot hybridisation. In 30 of the 35 cases the results of this hybridisation corresponded with the results of the dot blot hybridisation on the smears.