Disorders of sexual development with XY karyotype and female phenotype: clinical findings and genetic background in a cohort from a single centre.

PURPOSE: 46, XY disorders (or differences) of sex development (DSD) are a group of clinical conditions with variable genetic background; correct diagnosis is often difficult, but it permits to optimize the management. The aim of this study is to identify clinical and genetics features of a group of women with 46, XY DSD to define some issues characterizing people with 46, XY DSD in Italy. METHODS: Retrospective analysis of girls and women with 46, XY DSD and female phenotype evaluated between year 2000 and 2016, performed by anonymised database, focusing on the clinical features and management, including presentation, first diagnostic suspect, gonadal surgery and molecular diagnostic delay. RESULTS: A total of 84 records were collected (mean age at clinical presentation: 9.1 ± 7.9 years; mean age at definitive diagnosis: 20.1 ± 15.0 years). Complete androgen insensitivity syndrome was the most common diagnosis (60%). Only 12 patients (14.3%) did not receive a molecular diagnosis. Early misdiagnoses frequently occurred; diagnostic delay was 10.2 ± 11.2 years, being reduced in patients presenting from 2007 to 2016. The discordance between genotypic and phenotypic sex during pregnancy or at birth determined early reason for referral in a considerable percentage (4.9%). CONCLUSION: Misdiagnosis and long diagnostic delays are present in females with 46, XY DSD in Italy, but the new genetic techniques permit faster right diagnoses in the last years. The centralization in dedicated third level units permits to reduce the number of patients without a molecular diagnosis, allowing better clinical management and appropriate genetic counselling.

Rasmussen's encephalitis: From immune pathogenesis towards targeted-therapy.

Rasmussen encephalitis (RE) is a unilateral hemispheric encephalitis whose main clinical features include refractory focal epilepsy or epilepsia partialis continua, hemiparesis, and progressive cognitive decline. Despite the autoimmune pathogenesis of RE, the only definitive therapeutic option is currently represented by surgery. We review the clinical features, the immune pathogenesis, and the available therapeutic options for RE, with special focus on immunosuppressive agents. The research includes systematic reviews, meta-analyses, observational studies, clinical trials, cases series and reports, until 2020. The use of immunosuppressive agents in RE is supported by the evidence of an autoimmune involvement of the central nervous system in this condition. Although often insufficient to modify the disease course and to achieve symptomatic control, immune therapy can be effective in patients with slow disease progression or in patients in which surgery is not applicable. Moreover, the documentation of T-cell involvement in the pathogenesis of RE, with a specific cytokine pattern, opens a window of opportunity for the use of T-targeted therapies and biologic drugs (i.e. anti-TNFα agents) in the treatment of this disease.

Time-dependent effect of chlorhexidine surgical prep.

Despite continued advances in preoperative preventive measures and aseptic technique, surgical site infections remain a problem. The purpose of this study was to evaluate the time-dependent effectiveness of chlorhexidine, a common surgical preparation solution, at various concentrations. Agar plates containing a Mueller-Hinton medium were inoculated with Staphylococcus aureus (lux) bacteria. The bacteria are genetically engineered to emit photons, allowing for quantification with a photon-counting camera system. Standardized amounts of aqueous chlorhexidine at three different concentrations (group 1:4%; group 2:2%; group 3:0.4%) were applied to the agar plates and comparisons in bacterial reduction were made. After 2 min of contact time, groups 1 and 2 had similar reductions in bacterial load with 30% bacterial load remaining in each group (P=0.512), whereas group 3 had a significantly higher bacterial load (33%) when compared to both groups 1 and 2 (1 vs 3, P<0.0001; 2 vs 3, P=0.0002). The bacterial load in all three groups continued to decrease out to the final time point (1h) with group 1 having the least amount of bacterial load remaining, 9% (P<0.0001) and group 3 with the highest bacterial load remaining, 19% (P<0.0001). This study demonstrates two key results: first, dilution of chlorhexidine correlates directly with its bactericidal activity; second, its effectiveness is directly related to its contact time. Based on the results of this study, the authors recommend using 4% chlorhexidine for surgical site preparation and allowing a minimum of 2 min of contact time prior to making the skin incision.

An exploratory survey of eating behaviour patterns in adolescent students.

OBJECTIVE: Empirical research has always treated adolescents' eating habits from a variable-centered perspective, but this approach may miss the configurations of eating behaviours that uniquely describe discrete groups of individuals. The aim of this study was to investigate prototypical patterns of eating habits in a large sample of Italian adolescents and their behavioural and psychological correlates. METHOD: Data were gathered from 1388 students (F=60%, mean age 14.90±1.34 yrs), who were asked to fill in an original questionnaire surveying dietary habits, body weight attitudes, body image, sport activities and sources of information about food. Perfectionism, self-esteem, self-efficacy and care for food were also assessed as well-known psychological risk factors for Eating Disorders. RESULTS: Five prototypical eating behaviour patterns were identified through cluster analysis. Cluster membership was associated (p<0.05) with gender, age and age- and gender-correct BMI percentile, perceived relevance of physical appearance in achieving success in life; one's weight and body image evaluation, dieting, physical activity, self-efficacy, self-esteem and care for food. Clusters did not differ in perfectionism score and in frequency of consulting different sources of information about food and weight, except in the case of dieticians. CONCLUSION: The identification of prototypical eating habits patterns revealed a large range of wrong eating attitudes and behaviours among Italian adolescents. Such data suggest the need to develop and implement adequate prevention programs.

Self-reported psychological distress associated with steroid therapy for HIV.

Anabolic androgenic steroid (AAS) replacement therapy is standard care for patients with low testosterone, including HIV-related conditions. These medications have been associated with development of aggressiveness, anxiety disorders, and depression, but only in short-term clinical trials. We conducted an anonymous street survey at a gay and lesbian community event and a survey in a clinic-based setting to study the wider prevalence of psychiatric side-effects associated with androgenic steroids. In the street-based survey, almost half of those prescribed AAS reported psychological side-effects, most commonly aggression (29%) followed by depression (21%). In the clinic survey of mostly HIV+ male patients, changes in sex drive were the most commonly reported effect of treatment while impulsive aggression, anxiety and depression were reported at levels similar to those in the street fair survey. These findings suggest that AAS therapy may be more frequently associated with distress than has been reported in the clinical literature.

Minced beef and human salmonellosis: review of the investigation of three outbreaks in France.

The synthesis of investigations of three salmonellosis outbreaks which occured in France between 1998 and 2000 confirms the role of the consumption of minced beef and highlights the importance of prevention measures.

Neuroendocrine, immunohistochemical, and ultrastructural study of pineal region tumors.

Thirteen patients with tumors in the pineal region were submitted to pre- and post-operative blood sampling (08:00, 14:00, 20:00, and 02:00 hr) for three or four consecutive days. A single cerebrospinal fluid (CSF) sample was collected at surgery, and melatonin levels determined. In all patients, serum and CSF beta subunit of human chorionic gonadotrophin (betaHCG), carcino embryonic antigen (CEA), and alpha-fetoprotein (AFP) levels were measured. Histology revealed four pineocytomas, one pineoblastoma, four germinomas, one immature teratoma, one pilocytic astrocytoma, one lymphoma, and one meningioma. Serum and CSF levels of serological biomarkers were normal, except for one of the germinoma cases. In most patients, alteration either in the circadian rhythm or in the melatonin concentration was observed before surgery. In benign neoplasms the circadian rhythm was conserved. In pineoblastoma, lymphoma, and three out of four germinomas, melatonin concentrations were undetectable. In one case of germinoma, melatonin levels were high, with the circadian rhythm being abolished. According to conventional histology, all germinomas were similar. Therefore, in a rare case of pineal germinoma with high melatonin levels, the tissue was subjected to an in depth investigation (immunohistochemical and ultrastructural) in order to determine the pathology and the possible differences from the other typical germinomas. Results were compared to those provided from other pineal neoplasms. Electron microscopy examination detected the presence of clusters of intermediate filaments and numerous electrondense granules only in the case of a germinoma producing melatonin.

Cerebral rhabdomyosarcoma with rhabdoid tumor-like features.

The present paper describes a case of cerebral neoplasm presenting histological-immunohistochemical characteristics of malignant rhabdoid tumor (MRT) and ultrastructural features of both MRT and rhabdomyosarcoma (R). MRT was first described as an aggressive neoplasm of unknown histogenesis of the kidney, then many other sites of onset were reported, including the central nervous system. However, it has been shown that other tumors of known histogenesis can mimic histologic and ultrastructural features of MRT. On the basis of our findings we agree with authors who support the notion that extrarenal MRT has often a different histogenesis from MRT of kidney, and it probably is a 'phenotypic' entity rather than a distinct pathologic entity.

Metastatic oligodendroglioma. Case report.

We report a case of remote metastasis of oligodendroglioma. Similar cases are reported in the literature for malignant cerebral tumors. Our case seems rather different because of low grade histology. Potential malignancy was evidenced only by further investigations with labeling indexes.

Enterogenous cyst of the cervical canal: report of a case in a 68-year-old woman and review of the literature.

A case of a cervical enterogenous cyst in a 68-year-old woman with associated vertebral malformation is presented. The diagnostic value of Magnetic Resonance Imaging, positive reaction to Periodic-Acid-Schiff and immunohistochemical staining for carcinoembryonic antigen are emphasized. The literature is reviewed: controversies about embryogenic theories and classification of these lesions are discussed.

[Chronic kidney failure: dialysis and kidney transplantation. The medicolegal and social considerations]. / Insufficienza renale cronica: dialisi e trapianto renale. Considerazioni medico-legali e sociali.

The authors carried out a research on the social and labour problems of the people affected by chronic renal failure, either on dialysis treatment or already transplanted since two years. It has been given a questionnaire based on questions about the person, the working position, the social insurance situation, the family and personal problems. The results show a good social reinsert and a good recover of the transplanted in opposition of the many problems had by those on dialysis; in particular it has been considered also the problem of the periodic absences from work. It has been also considered the italian law situation regarding the people affected by chronic renal failure in some different social insurance fields.

The silent corticotropinoma: is clinical diagnosis possible?

Up to now, the diagnosis of silent corticotroph cell pituitary adenomas has been made only on histopathological basis. In this paper we describe 6 women affected with pituitary adenomas, without evident clinical features of hypercortisolism, in whom retrospective data suggested the possibility of clinically diagnosing silent corticotropinomas in vivo. In all patients basal ACTH and cortisol levels were normal, and the low-dose dexamethasone test constantly suppressed serum cortisol and urinary 17-hydroxycorticosteroid levels. The CRH and/or lysine-vasopressin tests, performed in five patients, always induced exaggerated ACTH/cortisol rises. In three cases the response to the opiate agonist loperamide was assessed and no inhibition of ACTH/cortisol levels was found. All patients underwent pituitary surgery. In five cases evidence of corticotropinoma was obtained by immunohistochemistry or immunofluorescence studies; moreover, in one adenoma ACTH was secreted into the culture medium, and in another one CRH and arginine-vasopressin induced a marked intracellular [Ca++] rise. Electron microscopy study of the adenoma, removed from three patients, showed the presence of adenomatous corticotroph cells. Finally, in another woman no hormonal abnormalities were initially observed and she was operated for a "nonfunctioning" pituitary adenoma, but four years later an overt Cushing's disease appeared, suggesting that a silent corticotropinoma subsequently became functional, although the formation of a different adenoma cannot be excluded. In conclusion, the occurrence of ACTH/cortisol hyperresponsiveness to CRH and/or lysine-vasopressin and the lack of suppression of ACTH/cortisol secretion to opioid agonists in patients with apparently "nonfunctioning" pituitary tumors might allow the in vivo recognition of silent corticotropinomas.

[Prognostic implications of the proliferation index (H3-TdR-labeling index) and ploidy in neuroectodermal tumors (astrocytomas and glioblastomas)]. / Implicazioni prognostiche dell'indice di proliferazione (3H-TdR-labeling index) e della ploidia nei tumori neuroectodermici (astrocitomi e glioblastomi).

Kinetic cellular methods were used in 53 cases of various sizes of astrocytomas and glioblastomas to obtain reliable prognostic information. Kinetic analysis revealed a wide variation of proliferative activity, with a gradual increase of the mean value from the most differentiated astrocytomas to glioblastomas. DNA content was significantly correlated with the degree of histological differentiation. Chromosomic patterns, which were detected in a few cases, were generally aspecific. The sole recurrent alteration in the karyotype was a small metacentric marker. The comparison of results obtained with the follow-up of patients showed that the labeling index offers a more accurate estimate of the proliferative potential of individual tumours, and thus of the probability of survival, than histological diagnosis and the evaluation of other biological parameters such as ploidy and karyotype.

[Minor donor of bone marrow graft: medico-legal aspects]. / Il donatore minorenne nel trapianto di midollo osseo: aspetti medico legali.

Bone marrow transplantation can provide long-term disease-free survival when used as therapy for a variety of lethal disorders. Authors discuss about the underage donor consent and review the literature. In conclusion they consider that Bone Marrow donation is too important to leave its decision only to parents; they suggest to institute professional committees that consider donor will and verify on which basis he expresses his consent.

Primary intracranial rhabdomyosarcoma: report of two cases.

Primary intracranial rhabdomyosarcoma (RMS) is a rare tumor in infancy and childhood that is found in various locations in the central nervous system. The clinical course worsens rapidly, and the final outcome is poor, with a median survival time of 8-10 months. Invasion of the meninges, spontaneous intratumoral bleeding, spinal leptomeningeal CSF spreading of tumor cells, and early recurrence of the mass are the distinctive features of RMS. Diagnosis of RMS may be missed: immunohistochemical staining using specific markers (myoglobin, myosin, desmin, vimentin, enolase), along with ultrastructural studies, provide the basis for making the final diagnosis. Treatment of RMS includes surgical excision, craniospinal radiation therapy, and chemotherapy. We report two cases of primary RMS in the CNS located in the posterior fossa and frontotemporal area. Both children underwent total surgical removal of the mass. Early recurrence of the tumor mass was noticed in both patients 2 months after surgery. Both children died shortly thereafter.