Androgen receptor expression in preputial dartos tissue correlates with physiological androgen exposure in congenital malformations of the penis and in controls.

INTRODUCTION: The androgen receptor (AR) plays an important role in the development of male genitalia, and impaired androgen signalling has been hypothesised to underlie congenital penile malformations (CPM) such as hypospadias. Previous studies exploring the role of AR expression in the development of CPM have yielded conflicting results. OBJECTIVES: To assess AR expression in human foreskin of boys/men born with hypospadias, buried penis versus controls. STUDY DESIGN: Foreskin samples of 428 boys and men undergoing primary penile surgery (198 controls, 197 hypospadias, and 33 buried penis) were collected between October 2013 and July 2018. AR staining was performed in all samples and semi-quantitatively scored by two researchers independently, using a modified quick score (mQuicks) that assesses the proportion and intensity of AR staining in smooth muscle fibres. RESULTS: The interobserver variability of the mQuicks had a high level of agreement for the total score, as well as for the subscores. Two phases of high AR expression were observed in all groups, the first following the postnatal gonadotropin surge (i.e., mini-puberty) and the second in (pre-) puberty. No differences in AR expression were found in hypospadias or buried penis cases as compared to controls matched for age at time of surgery. DISCUSSION: This study describes the physiological evolution in AR expression in the human foreskin of boys with CPM and explains the cause of the previously reported, conflicting results. Despite the very large cohort, the limitations of this study are the low number of cases younger than six months at the time of surgery and the lack of Tanner stages to correlate with the mQuicks in adolescents. CONCLUSIONS: The mQuicks is a straightforward and informative tool to semi-quantitatively assess AR expression in the dartos tissue. In this study, AR expression in human foreskin shows a bimodal distribution in boys with CMP and controls, following physiological androgen exposure. No statistically significant difference in AR expression could be found between both groups. Whether other local mechanisms are affected by these physiological changes is currently unclear. However, strict age-matching should be considered when exploring the mechanisms underlying disturbed penile and urethral development in CMP.

Routine histopathological examination after female-to-male gender-confirming mastectomy.

BACKGROUND: The number of transmen seeking gender-confirming surgery has risen steadily throughout the last decade. Pathologists are increasingly confronted with transmale mastectomy specimens. It is not clear whether routine histopathological examination is useful. This study explored the possible benefit of routine investigation through detailed description of lesions encountered in mastectomy specimens after female-to-male gender-confirming surgery. METHODS: Breast tissue from a cohort of transmen was reviewed. The presence of benign and malignant breast lesions was recorded. The number of terminal duct-lobule units (TDLUs) per ten low-power fields (LPFs) was quantified. Information on hormone therapy and morphometry was retrieved for selected patients. RESULTS: The cohort included 344 subjects with a mean age of 25·8 (range 16-61) years at the time of surgery; the age at surgery decreased significantly over time. Older individuals presented with a significantly higher number of breast lesions. The number of TDLUs per LPF was lower in heavier breasts, but did not correlate with age. Breast lesions, either benign or malignant, were present in 166 individuals (48·3 per cent). Invasive breast cancer was found in two (0·6 per cent); one tumour was an unexpected finding. The number of breast lesions encountered on histopathological examination increased significantly when more tissue blocks were taken. CONCLUSION: The discovery of an unexpected breast cancer in a 31-year-old transman emphasizes the importance of thorough routine histopathological examination of mastectomy specimens. The number of tissue blocks taken should be based on age and breast weight.

Identifying a consensus sample type to test for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis and human papillomavirus.

OBJECTIVES: Sexually transmitted infections (STIs) are a global cause of acute illness. Early detection plays a crucial role in interrupting transmission and preventing complications. However, the accessibility of STI testing is curbed by the lack of an overall preferred sample type. By means of a prospective study in female sex workers (FSW), we compared the sensitivity of samples from different anatomical sites in detecting Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Mycoplasma genitalium and human papillomavirus. Besides, we documented the prevalence of each STI in this high-risk population. METHODS: We selected 303 FSW and tested them for each STI by nucleic acid amplification testing on two vaginal and cervical swabs from different manufacturers, cervical smear and first-void urine. The sensitivity of each sample type was compared for each infectious agent in order to identify a consensus sample type. RESULTS: Vaginal swabs were superior to all other sample types, with an overall sensitivity of 86%. The sensitivity was the lowest for first-void urine, detecting only 63% of positive cases. The prevalence was 3.3% (10/299) for Neisseria gonorrhoeae; 9.0% (27/299) for Chlamydia trachomatis; 7.4% (22/298) for Trichomonas vaginalis; 10.8% (32/296) for Mycoplasma genitalium and 55.6% (158/284) for human papillomavirus. CONCLUSIONS: When testing for STIs, vaginal swabs are the sample of choice and first-void urine should be avoided. Designating (self-sampled) vaginal swabs as a consensus sample type enables harmonization of STI testing and extension of testing to large numbers of unscreened females.

Serum vascular cell adhesion molecule-1 predicts significant liver fibrosis in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and is strongly associated with obesity, dyslipidemia and insulin resistance. NAFLD often presents as simple steatosis (NAFL) but can progress to non-alcoholic steatohepatitis (NASH) and fibrosis. Current non-invasive biomarkers are not tailored to identify significant (⩾F2) fibrosis, although recent guidelines recommend a stringent follow-up of this patient population. We and others have reported on the role of pathological angiogenesis in the pathogenesis of NAFLD, highlighting pro-angiogenic factors as potential diagnostic markers. OBJECTIVE: To investigate the applicability of angiogenic and endothelial dysfunction markers as non-invasive diagnostic tools for NASH or NASH-associated fibrosis in obese patients. METHODS: In a prospective cross-sectional study, male patients undergoing bariatric surgery (n=61) and control patients (n=35) were recruited. Serum protein levels and visceral adipose tissue gene expression of endothelial dysfunction and angiogenic markers were analyzed by multiplex bead-based assay and quantitative RT-PCR, respectively. For validation, we recruited a second cohort of patients undergoing bariatric surgery (n=40) and a cohort of NAFLD patients from our outpatient clinic (n=30). RESULTS: We identified serum vascular cell adhesion molecule-1 (VCAM-1) as an independent predictor for ⩾F2 fibrosis (median 14.0 vs 8.7 ng ml-1 in patients with and without significant fibrosis; P<0.0001) with an area under the receiver-operating characteristics (AUROC) curve of 0.80. The cutoff point of 13.2 ng ml-1 showed a sensitivity of 80% and specificity of 83%. In line with these results, VCAM-1 visceral adipose tissue gene expression was also elevated in patients with fibrosis (P=0.030). In the bariatric surgery and clinical validation cohorts, VCAM-1 displayed similar AUROCs of 0.89 and 0.85, respectively. CONCLUSIONS: VCAM-1 levels are able to accurately predict significant (⩾F2) fibrosis in NAFLD patients.

Congenital penile pathology is associated with abnormal development of the dartos muscle: a prospective study of primary penile surgery at a tertiary referral center.

PURPOSE: Pathophysiological mechanisms leading to chordee in patients with hypospadias and to the hidden state of buried penis in the prepubic fat remain unclear. Resection of dartos tissue usually makes the penis straight in patients with hypospadias and corrects it in those with buried penis, suggesting a common pathophysiology related to dartos tissue. MATERIALS AND METHODS: Tissue samples from 113 children undergoing primary penile surgery for hypospadias (94 patients), epispadias (1) or buried penis (18) were collected between November 2011 and September 2013. Tissue samples from 79 children undergoing circumcision for nonmedical reasons served as controls. All samples were stained with smooth muscle actin and analyzed by the same pathologist, who was blinded to indication for surgery. Chi-square and Fisher exact tests were applied. RESULTS: Three different dartos tissue patterns were observed. Pattern I (normal) consisted of smooth muscle fibers of dartos tissue organized in a parallel configuration in the subcutaneous tissue. Pattern II was characterized by poorly developed and hypotrophic smooth muscle fibers. Pattern III was determined by randomly distributed smooth muscle fibers in the subcutaneous tissue, without parallel configuration. Pattern I was observed in 45 circumcision specimens (64%). Of buried penis cases 78% were considered abnormal (pattern II in 4 cases and III in 10, p = 0.001). Of hypospadias cases 70% were considered abnormal (pattern II in 31 cases, III in 32, and mixed II and III in 3, p < 0.001). The only epispadias case was designated pattern II. CONCLUSIONS: Congenital penile pathology (hypospadias, buried penis) is associated with structural anomalies in dartos tissue. Further research is needed to unveil the pathophysiology of the condition.

Diagnostic potential of open lung biopsy in mechanically ventilated patients with diffuse pulmonary infiltrates of unclear aetiology.

Acute respiratory failure with bilateral pulmonary infiltrates is a clinical problem with a wide differential diagnosis. We evaluated whether open lung biopsy offered a diagnosis and therapeutic guidance in cases of unclear diagnosis after non-invasive tests. For this purpose, we reviewed 60 cases of open lung biopsy performed between 2002 and 2009 in patients with acute respiratory failure and bilateral infiltrates at the intensive care unit of Ghent University Hospital. Pathological diagnosis was classified as specific or non-specific and its contribution to therapy and decision-making was evaluated by a panel of three intensive care unit physicians. We found that a specific pathological diagnosis was present in 39 open lung biopsy patients (65%; 95% confidence interval 52 to 76%): idiopathic interstitial pneumonia in 24 patients, malignancy in four patients, pulmonary infectious disease in nine patients, and a combination of specific diagnoses in two patients. Open lung biopsy contributed to patient management in 53 cases (88%) as it led to the initiation, modification or discontinuation of therapeutic drugs in 36, and contributed to the decision to continue or withdraw ventilator support in 17. Complications of open lung biopsy were noted in 14 patients (23%). We conclude that open lung biopsy was a useful diagnostic intervention in of a selected group of patients with acute respiratory failure and bilateral infiltrates of unclear clinical diagnosis, as it offered a specific diagnosis in 65%.

Questioning the Pathogenic Role of the GLA p.Ala143Thr "Mutation" in Fabry Disease: Implications for Screening Studies and ERT.

Fabry disease is an X-linked inborn error of glycosphingolipid metabolism caused by quantitative or qualitative defects in the lysosomal enzyme alfa-Galactosidase A (aGAL A), ultimately resulting in vital organ dysfunction. Mainly the kidneys, the heart, and the central nervous system are involved. While the classical phenotype of Fabry disease is readily recognizable, screening studies have identified clinical variants. Here, we report the phenotype associated with the GLA p.Ala143Thr (c.427G>A) mutation in 12 patients aged 42-83 years. None of the patients had classical Fabry signs or symptoms as angiokeratoma, hypohidrosis, acroparesthesia, or cornea verticillata. Possible Fabry manifestations were renal failure (5/12), stroke (7/12), and left ventricular hypertrophy (5/12), but these were not necessarily attributable to the p.Ala143Thr mutation, as a cardiac biopsy in one female and left ventricular hypertrophy and kidney biopsies in two males with renal failure and microalbuminuria lacked Gb-3 deposits. The literature data on this mutation as well as data collected in the Fabry Outcome Survey (FOS) database confirm these findings. The association of renal failure, stroke, and left ventricular hypertrophy with this mutation could be the result of selection bias, as most patients were detected in screening studies.We conclude that care should be taken with attribution of vital organ dysfunction to GLA sequence alterations. In case of the p.Ala143Thr mutation, and possibly also other mutations associated with an attenuated phenotype, diagnostic tools such as biopsy and imaging should critically evaluate the relation of end-organ failure with Fabry disease, as this has important consequences for enzyme replacement therapy.

Arguments for an increasing differentiation towards fibrocartilaginous components in midportion Achilles tendinopathy.

PURPOSE: The objective of this study was to investigate the fibrocartilaginous differentiation occurring in midportion Achilles tendinopathy. METHODS: Tendon samples were retrospectively collected from 23 patients, who had undergone surgery for midportion Achilles tendinopathy resistant to conservative treatment. Based on histological scores, the biopts were subdivided into three categories: a light, moderate and severe histopathological stage. Throughout these stages, immunohistochemical staining was performed against biglycan, aggrecan and collagen type II, components characteristic for fibrocartilage. Staining of these components was evaluated using a semi-quantitative scoring method. RESULTS: The immunohistochemical scores of biglycan and aggrecan were statistically significant between the histopathological stages (P < 0.001). The immunohistochemical scores were positively correlated with the increasing histopathological stages [Spearman's correlation coefficient = 0.93 for biglycan and 0.78 for aggrecan (P < 0.001)]. Staining for collagen type II remained negative throughout these stages. CONCLUSION: Immunohistochemical staining of the fibrocartilaginous components biglycan and aggrecan showed a progressive increase, correlated with a further evolved histopathological stage. This observation gave arguments for an increased differentiation towards fibrocartilaginous components at protein level in midportion Achilles tendinopathy.

Are EUS-FNA and EBUS-TBNA specimens reliable for subtyping non-small cell lung cancer?

With endosonography, the diagnosis and staging of non-small cell lung cancer (NSCLC) increasingly relies on small samples. The discrimination between squamous and non-squamous subtypes is now important for therapy tailoring. We analyzed the agreement between fine needle aspirates obtained by endosonography and matched biopsy samples for subtyping NSCLC. Patients with a positive endoscopic fine needle aspirate and a matched biopsy were identified. The level of diagnostic agreement was estimated with biopsy samples as golden standard. In 951 patients investigated with endosonography, we identified 92 with NSCLC on the positive fine needle aspirate and on the matched biopsy. Squamous cell carcinoma was diagnosed in 34 (37%) and 44 (48%) of fine needle aspirate and biopsy samples; while non-squamous carcinoma was diagnosed in 58 (63%) and 48 (52%) respectively. The agreement between needle aspirate and biopsy for the subtyping of NSCLC was 76% (kappa=0.52). In cases with cell block preparation, the agreement for subtyping was 96% (kappa=0.91) vs 69% (kappa=0.39) in cases without cell blocks. Therefore, the diagnostic agreement between endosonographic fine needle aspirates and biopsy specimens for subtyping NSCLC is moderate with a disagreement in 1 out of 4 patients. However, cell block preparation increased the agreement and thus the reliability of the fine needle specimens obtained during endosonography, for subtyping NSCLC considerably. In conclusion, for patients with NSCLC in whom subtyping is relevant, a diagnostic technique yielding larger samples (FNA with cell block preparation or biopsies) should be preferred.

Microscopic polyangiitis involving the breast.

We report a case of a 76-year-old woman, presenting with a persistent dry cough, subfebrility, arthralgia and myalgia, weight loss and a breast lesion. She has elevated inflammatory parameters, impaired renal function with proteinuria, bilateral lung nodules on computed tomography scan (CT scan) and a suspect lesion on mammography. A diagnosis of microscopic polyangiitis with involvement of the breast is made based on clinical and radiographic findings, with positive auto-immune serology and histological confirmation. Although vasculitis of the breast is uncommon, this case illustrates that when a breast lesion is found, in combination with constitutional symptoms, we should think about the possibility of an anti-Neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. Therefore it may be important to perform auto-immune serology in these cases before proceeding to major surgery.

Cytology of the 'penile' neovagina in transsexual women.

OBJECTIVE: The primary objective was to describe the neovaginal cytology in transsexual patients (n = 50) treated with the inverted penile skin technique. Secondary objectives were to compare our cytological findings with patient characteristics including use of oestrogens, sexual orientation and penetrative intercourse. METHODS: The medical and surgical history, sexual orientation and whether there was a current relationship were ascertained. A speculum examination was followed by microscopy of a Pap smear of the neovaginal vault. RESULTS: Well-preserved nucleated squamous cells were found in 72%. The correlation between their presence and sexual orientation was highly significant (P = 0.016), with those not sexually interested and homosexually oriented all having nucleated cells on the Pap smear. However, the correlation between these cells and penetrative intercourse failed to reach significance. Four samples showed atypical squamous cells of undetermined significance, all were negative for high-risk human papillomavirus (HR-HPV) types. One patient showed a low-grade squamous intraepithelial lesion that was HR-HPV positive. There was a significant correlation between the presence of cytological lesions and sexual orientation (P = 0.006). Four percentage of the specimens showed Döderlein bacilli. Inflammation was found in 30.6% of samples with squamous cells. CONCLUSIONS: The penile skin-lined neovagina of transsexual women can reflect the cytological findings present in biological women. However 'normal' cervical cytology, with superficial, intermediate and parabasal cells as well as Döderlein bacilli, was found in only 4% of transsexual women. Although one patient's Pap test showed koilocytes and was HR-HPV positive, no high-grade squamous intraepithelial lesions were identified.

Influence of an increased intracranial pressure on cerebral and systemic haemodynamics during endoscopic neurosurgery: an animal model.

BACKGROUND: During endoscopic neurosurgery, direct mechanical stimulation of the brain by the endoscope and increased intracranial pressure (ICP) caused by the continuous rinsing can induce potentially lethal haemodynamic reflexes, brain ischaemia, and excessive fluid resorption. METHODS: In a newly presented rat model of endoscopic neurosurgery, stereotactic access to the cerebrospinal fluid was secured and the ICP was increased by controlled infusion until complete suppression of the cerebral perfusion pressure (CPP). The haematocrit (Hct) level was determined before and after the procedure. During the whole procedure, invasive arterial pressure, ICP, and heart rate were continuously recorded and evaluated in a subsequent offline analysis. After the procedure, the animals were allowed to recover and 7 days later they were killed for histological examination. RESULTS: Suppression of the CPP resulted in a severe hypertension combined with tachycardia or mild bradycardia. The Hct decreased from 41 to 35 over the minutes of CPP suppression. After cessation of the infusion, the ICP decreased to 37% of the plateau pressure within 2.5 s. In the first few minutes after restoration of normal ICP, five animals died because of pulmonary oedema. CONCLUSIONS: Upon complete suppression of the CPP, an obvious hypertension developed, often together with tachycardia, but no severe bradycardia. At high ICP levels, we observed an important translocation of irrigation fluid to the vascular space. Fatality was not caused by ischaemia or arrhythmia but due to pulmonary oedema.

Prediction of recurrent disease by cytology and HPV testing after treatment of cervical intraepithelial neoplasia.

OBJECTIVE: To assess the role of human papillomavirus (HPV) testing and cytology as predictors of residual/recurrent disease after treatment of high-grade cervical intraepithelial lesions. METHODS: One hundred and thirty-eight women with cervical intraepithelial neoplasia (CIN) grade 2/3 lesion on biopsy were included in a prospective follow-up study in Belgium and Nicaragua. All women were treated with loop electrosurgical excision procedure (LEEP) and follow-up visits took place at 6 weeks, 6 months, 1 year and 2 years. During these visits, a Papanicolaou (Pap) smear test was taken, colposcopy was performed and specimens were collected for HPV testing. Cytology, high-risk (HR) HPV presence, persistent HR HPV infection and combinations of these tests at different time points during follow-up were correlated with histologically confirmed residual/recurrent disease. RESULTS: Thirteen patients (9%) developed residual/recurrent disease during follow-up. Abnormal cytology at 6 weeks after treatment was significantly correlated with residual/recurrent disease. Nine of thirty-seven patients with abnormal cytology at 6 weeks had recurrent disease versus three of seventy with a normal cytology [odds ratio (OR): 7.2; 95% confidence interval (CI): 1.8-28.5; P = 0.003). Sensitivity of this test was 75.0%, specificity 70.5%. Combining abnormal cytology and the presence of HR HPV within the first 6 months after treatment gave the best correlation with residual/recurrent disease: of the 54 women with abnormal cytology and/or HR HPV presence within the first 6 months, 11 developed residual/recurrent disease (OR 10.2; 95% CI: 2.2-48.3). Sensitivity of this combination was 84.6% and specificity 65.0%. CONCLUSION: Cytology remains the cornerstone in the early follow-up after LEEP for CIN lesions of the cervix. HPV testing can add value as it increases the sensitivity of cytology in concomitant testing within the first 6 months.

Telomere biology in giant cell tumour of bone.

Giant cell tumour of bone (GCTB) is a benign bone tumour known for the unpredictable clinical behaviour of recurrences and, in rare instances, distant metastases. It consists of uniformly distributed osteoclastic giant cells in a background of mononuclear rounded and spindle-shaped cells. Cytogenetically, telomeric associations are the most common chromosomal aberrations, which, however, are normally almost exclusively found in high-grade malignancies. GCTB has often been regarded as a polyclonal tumour, but more recently a recurrent specific aberration was reported, which suggests a possible role for disturbed telomere maintenance. Here we further investigate telomere maintenance in GCTB using 19 samples from 19 patients. A combination of immunofluorescence and FISH was performed, applying antibodies directed against promyelocytic leukaemia body-related antigen and hTERT and using telomere peptide nucleic acid probes. The TRAP assay and telomere restriction fragment length analysis were performed for functional detection of telomerase activity and alternative telomere lengthening. Both osteoclastic giant cells and mononuclear cells showed positivity for hTERT and promyelocytic leukaemia body-related antigen. In most mononuclear cells, co-expression was present. The TRAP assay demonstrated heterogeneous telomerase activity, while telomere restriction fragment length analysis showed non-heterogeneous telomere lengths, indicating the absence of alternative telomere lengthening. Confocal microscopy showed stereometric co-localization of nucleolin with promyelocytic leukaemia body-related antigen in association with telomeres in the spindle-shaped cells. hTERT was more diffusely distributed throughout the nucleus. Our results show that GCTB demonstrates remarkable telomere maintenance of activated telomerase and inactivated alternative telomere lengthening in the presence of normal mean telomere restriction fragment lengths. These findings strongly suggest that these aggregates, while activating telomerase, are part of a structural telomere protective-capping mechanism rather than of a telomere-lengthening mechanism. Telomere maintenance could be considered an important key factor in the pathogenesis of GCTB.

[Human papillomavirus genotype profile in Kinshasa, Democratic Republic of the Congo: implications for vaccination]. / Profil génotypique du papillomavirus humain rencontré dans l'environnement de Kinshasa: intérêt vaccinal.

UNLABELLED: Proposed anti-human papillomavirus (HPV) vaccines, i.e., Cervarix (Glaxomith-Kline) and Gardasil (Merck), are designed to prevent infection by two high-risk HPV types, i.e., 16 and 18, for which estimation mainly in Western Europe and North America have demonstrated a prevalence 60 to 70%. OBJECTIVE: The purpose of this study was to determine the genotype profile of HPV strains encountered in the women of childbearing age in Kinshasa, Democratic Republic of the Congo and discuss the implications of this profile for anti-HPV vaccination. METHODS: Data and specimen collection was carried out at a voluntary HIV screening and treatment facility. Genotyping of HPV was performed in 55 patients presenting dysplastic lesions of the uterine cervix including 47 (85.5%) who were HIV-seropositive. Detection and typing of HPV were performed using the Inno-Lipa technique (Innogenetics Line Probe Assay) from Glaxo-Smith-Kline. RESULTS: Tests for HPV were positive in 54 patients (98.2%). A total of 153 HPV strains were isolated. Twenty-three HPV types were identified including 83.0% with high oncogenic activity. In order of frequency the oncogenic types were as follows: 68, 35, 51, 52, 16, 31, 18, 17, 33, 45, 56, 58 and 59. Strain frequency per patient ranged from 1 to 8 (mean +/- standard deviation, 2.8 +/- 2,0). Types 16 and 18 accounted for 11.8% of the isolated strains (18/153) and were observed in 33.3% of patients (18/54). CONCLUSION: The findings of this study suggest that the HPV genotype profile in Kinshasa differs from the profile observed in Western Europe and North America. If confirmed by larger-scale studies, this result bodes poorly for the efficacy of anti-HPV vaccines in Kinshasa.

Profil genotypique du papillomavirus humain rencontre dans l'environnement de Republique democratique du Congo : interet vaccinal

Les vaccins anti-HPV proposés, Cervarix® de Glaxo-Smith-Kline et Gardasil® deMerck, ciblent deux types du HPV à haut risque, le 16 et 18, dont la prévalence a été évaluée surtout en Europe de l'Ouest et enAmérique du Nord entre 60 et 70%. L'objectif de l'étude était de caractériser génétiquement les souches du HPV rencontrées dans la population des femmes en âge de procréer vivant à Kinshasa et d'en discuter les conséquences sur le plan de la vaccination anti-HPV. La collecte des données et le prélèvement des spécimens s'étaient déroulés à Kinshasa dans des sites de dépistage volontaire et du traitement duVIH. Le génotypage du HPV était conduit sur 55 cas portant des lésions dysplasiques du col utérin, dont 85,5%(47/55) étaient séropositifs pour le VIH. La détection et le typage du HPV étaient réalisés par la technique Inno-Lipa® (Innogenetics Line ProbeAssay) de Glaxo-Smith-Kline. La recherche du HPV était positive chez 98,2%(54/55) des patientes ; sur 153 HPV isolés, 23 types de HPV étaient identifiés dont 83,0%(127/153) à haut pouvoir oncogène, en ordre décroissant de fréquence suivant : 68, 35, 51, 52, 16, 31, 18, 17, 33, 45, 56, 58 et 59. La fréquence des souches trouvées par patiente variait de 1 à 8 (moyenne ± écart-type : 2,8 ± 2,0). Les types 16, 18, représentant 11,8%des isolats (18/153), ont été détectés chez 33,3%(18/54) des patientes. Le spectre génotypique du HPV trouvé à Kinshasa semble différent de celui trouvé en Europe et en Amérique du Nord. Ce résultat, s'il est confirmé par des études plus étendues, présage une faible efficacité des vaccins anti-HPV dans l'environnement de Kinshasa

Diagnostic des dysplasies cervicales associees a l'infection VIH : perte d'efficacite de la cytologie conventionnelle

Problematique : l'absence d'un programme national de depistage du cancer du col uterin en Republique Democratique du Congo ne permet pas de prendre en charge efficacement cette pathologie dont le risque est de surcroit amplifie par l'infection a VIH. Le choix des techniques diagnostiques se pose de facon critique surtout en condition de faibles ressources ou se trouvent la plupart des pays subsahariens. Objectifs de la recherche : Evaluer ; d'une part; les qualites diagnostiques des frottis conventionnels (FC); facilement realisable en conditions de faibles ressources comparativement aux frottis en couche mince (FCM) pris comme reference; et d'autre part; l'influence de l'infection par le VIH sur les performances de ces techniques diagnostiques. Methodologie : Les examens cytopathologiques cervicaux ont ete realises sur 128 patientes VIH et 132 patientes VIH+ consentantes selectionnees dans deux centres de depistage volontaire de VIH a Kinshasa. Le consentement eclaire etait obtenu apres conseil et explication sur l'interet de cet examen pour la femme en activite sexuelle. Resultats : Les lesions dysplasiques de haut grade et les cancers du col uterin (CCU) etaient 10;3 fois plus frequentes chez les sujets VIH+ comparativement aux sujets VIH- (Odds ration=10;3 ; IC95=3;7 a 31;1). La sensibilite; la specificite; les valeurs predilectives positive et negative; et l'efficacite diagnostique des FC etaient respectivement de 66; 7; 98;2; 87;6; 89;4pour les sujets VIH+ contre 80;0; 100; 100;0; 99;2et 99;2pour les sujets VIH-. Le risque de faux negatif comparativement aux risque de faux positifs etait significativement plus eleve chez le sujets VIH+ (x2 de Mc; Nemar = 10;3 ; p = 0;001) que chez les sujets VIH- (x2 de Mc; Nemar = 0 ; p = 1). Conclusion : La sensibilite; l'efficacite diagnostique des FC; d'une part; le taux de concordance (Kappa entre les FC et les FCM; d'autre part; etaient effondrees en presence de l'infection par le VIH; occasionnant un taux eleves de faux negatifs et une faible valeur predilective negative; probablement du fait de l'intensification des reactions inflammatoires. La frequence des examens de controle devrait etre plus rapprochee en cas d'infection a VIH

A rapid test of alloreactivity based on interleukin-2 mRNA expression might identify liver transplant recipients with donor-specific hyporesponsiveness.

BACKGROUND: Immunosuppression withdrawal is feasible in some liver transplant (OLT) recipients but may lead to severe rejection in others, underlying the need for reliable biomarkers to identify patients with tolerant profile in whose weaning/withdrawal could be safely proposed. We evaluated the value of real-time polymerase chain reaction (PCR)-based measurement of interleukin (IL)-2 mRNA in mixed lymphocyte reaction (MLR) to monitor in vitro anti-donor reactivity in OLT patients. METHODS: MLR were performed in three patients undergoing living donor OLT using a tolerogenic protocol including donor stem cells. IL-2 mRNA production in MLR was measured by PCR at several intervals after OLT. RESULTS: In the early posttransplant period, three patients presented with global immunodeficiency, as indicated by low IL-2 mRNA production against both donor and third-party antigens. In the two patients who has immunosuppression successfully withdrawn, donor-specific hyporesponsiveness was observed thereafter: IL-2 mRNA production against donor cells remained low, while IL-2 mRNA production against a third-party antigen-presenting cells progressively recovered. No such modulation of the anti-donor response was observed in the patient in whom withdrawal led to rapid rejection. CONCLUSION: Measurement of IL-2 mRNA production in MLR might prefer a tool to monitor anti-donor reactivity after OLT for decisions to minimize or withdraw immunosuppression in patients displaying donor-specific hyporesponsiveness.