Complete urological evaluation including sperm DNA fragmentation in male systemic lupus erythematosus patients.

OBJECTIVE: To evaluate sperm DNA fragmentation analysis in non-azoospermic male systemic lupus erythematosus (SLE) patients. METHODS: Twenty-eight consecutive male SLE patients (American College of Rheumatology criteria) and 34 healthy controls were evaluated for demographic/exposures data, urological evaluation, hormone profile and sperm analysis (including sperm DNA fragmentation). Clinical features, disease activity/damage scores and treatment were also evaluated. RESULTS: The median age (33 (20-52) vs. 36.5 (25-54) years, P = 0.329) and frequency of varicocele (25% vs. 32%, P = 0.183) were similar in SLE patients and healthy controls. Sperm DNA fragmentation showed significantly higher levels of cells class III (44 (9-88) vs. 16.5 (0-80)%, P = 0.001) and cell class IV (10.5 (3-86) vs. 7 (0-36)%, P = 0.039) in SLE. The sperm DNA fragmentation index was also significantly higher in SLE patients (62 (31-97) vs. 25.5 (0-100)%, P < 0.001). Conventional sperm parameters (including sperm count, motility and morphology) were similar in both groups. In SLE patients no correlations were observed between sperm DNA fragmentation index and age, disease duration, Systemic Lupus Erythematosus Disease Activity Index 2000 and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index scores, and cumulative dose of prednisone, hydroxychloroquine, intravenous cyclophosphamide, methotrexate, azathioprine and mycophenolate mofetil ( P > 0.05). Further analysis of SLE patients treated with and without intravenous cyclophosphamide showed that total sperm motility was significantly lower in the former group (64% (15-83) vs. 72% (57-86), P = 0.024). The sperm DNA fragmentation index was alike in both groups (52.5 (31-95) vs. 67.5 (34-97)%, P = 0.185). CONCLUSIONS: To our knowledge, this is the first demonstration that male non-azoospermic SLE patients have increased sperm DNA fragmentation without evident gonadal dysfunction. Intravenous cyclophosphamide does not seem to be a major determinant for this abnormality. Future prospective study is necessary to determine the impact of this alteration in these patients' fertility.

A new method to integrate ZnO nano-tetrapods on MEMS micro-hotplates for large scale gas sensor production.

A new method, which is easily scalable to large scale production, has been developed to obtain gas sensor devices based on zinc oxide (ZnO) nanostructures with a 'tetrapod' shape. The method can be easily extended to other kinds of nanostructures and is based on the deposition of ZnO nanostructures through polymeric masks by centrifugation, directly onto properly designed MEMS micro-hotplates. The micromachined devices, after the mask is peeled off, are ready for electrical bonding and sensing test. Sensor response has been successfully measured for some gases and volatile organic compounds with different chemical properties (ethanol, methane, nitrogen dioxide, hydrogen sulfide).

Impact of body mass index, age and varicocele on reproductive hormone profile from elderly men.

OBJECTIVES: To study the impact of obesity, age and varicocele on sexual hormones of adult and elderly men. MATERIALS AND METHODS: 875 men who were screened for prostate cancer were enrolled in this study. Data recorded comprised age, body mass index (BMI), serum levels of total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and follicular stimulating hormone (FSH). Patients were divided in groups according to their BMI in underweight, normal weight, overweight and obese grades 1, 2 or 3. First, it was studied the association between age, BMI, and hormone profile. Then, clinical varicocele was evaluated in 298 patients to assess its correlation to the others parameters. RESULTS: Obese patients had lower levels of TT, FT and SHBG (p<0.001) compared to underweight or normal weight patients. There were no differences in age (p=0.113), FSH serum levels (p=0.863) and LH serum levels (p=0.218) between obese and non-obese patients. Obese grade 3 had lower levels of TT and FT compared to obese grade 1 and 2 (p<0.05). There was no difference in the SHBG levels (p=0.120) among obese patients. There was no association between varicocele and BMI; and varicocele did not impact on testosterone or SHBG levels. CONCLUSIONS: Men with higher BMI have a lower serum level of TT, FT and SHBG. The presence of clinical varicocele as well as its grade has no impact on hormone profile in elderly men.

Primary antiphospholipid syndrome: morphofunctional penile abnormalities with normal sperm analysis.

OBJECTIVE: To perform a global gonadal and sexual functions assessment in primary antiphospholipid syndrome (PAPS) patients. METHODS: A cross-sectional study was conducted in 12 male PAPS patients and 20 healthy controls. They were assessed by demographic data, clinical features, systematic urological examination, sexual function, testicular ultrasound, seminal parameters according to the World Health Organization (WHO), seminal sperm antibodies, and hormone profile, including follicle stimulating hormone (FSH), luteinizing hormone (LH), morning total testosterone, and thyroid hormones. RESULTS: The median of current age and age of spermarche were similar in PAPS patients and controls (37.5 vs. 32.4 years, p = 0.270, and 13.1 vs. 12.85 years, p = 0.224, respectively), with a higher frequency of erectile dysfunction in the former group (25% vs. 0%, p = 0.044). Further analysis of PAPS patients with and without previous arterial thrombosis demonstrated that the median penis circumference was significantly lower in PAPS with arterial thrombosis than in PAPS without this complication (8.1 [6-10] vs. 10.2 [10-11] cm, p = 0.007). In addition, the median penis circumference was significantly lower in PAPS patients with erectile dysfunction than in patients without this complication (7.5 [6-9.5] vs. 9.5 [7.5-11] cm, p = 0.039). Regarding seminal analysis, the median sperm concentration, sperm motility, and normal sperm forms by WHO guidelines were comparable in PAPS patients and controls (141.5 [33-575] vs. 120.06 [34.5-329] × 10(6)/ml, p = 0.65; 61.29 [25-80] vs. 65.42 [43-82]%, p = 0.4; 21.12 [10-42.5] vs. 23.95 [10-45]%, p = 0.45, respectively), and none of them had oligo/azoospermia. No differences were observed between PAPS patients and controls regarding the frequency of antisperm antibodies, testicular volume by ultrasound, or hormone profile (FSH, LH, morning total testosterone, and thyroid hormone) (p > 0.05). CONCLUSIONS: Normal testicular function has been identified in PAPS patients, in spite of morphofunctional penile abnormalities. Previous arterial thrombosis may underlie penile anthropometry alteration.

Gonadal function in male patients with ankylosing spondylitis.

OBJECTIVE: To assess reproductive function in male ankylosing spondylitis (AS) patients in comparison to healthy controls. METHODS: Twenty AS patients were compared to 24 healthy male subjects with regard to demographic data, urological examination, testicular ultrasound (US), semen analysis, anti-sperm antibodies, and hormone profile. Exclusion criteria were present use of sulfasalazine or methotrexate, and ever use of biological/cytotoxic agents. Disease activity of AS was evaluated by clinical and laboratory assessments. RESULTS: Demographic data were similar in AS and controls (p = 0.175). Varicocele was found significantly more frequently in AS patients than in controls (40% vs. 8%, p = 0.027). Semen analysis revealed no significant differences in sperm quality between AS patients and controls (p > 0.05). By contrast, the median of normal sperm forms was significantly lower in AS patients with vs. those without varicocele [13.5 (range 2-27) vs. 22 (range 10-32.5)%, p = 0.049] whereas no difference in sperm morphology was observed comparing AS patients and controls without varicocele (p = 0.670). Comparison of AS patients with and without varicocele showed that anti-sperm antibodies, hormones, inflammatory markers, and disease activity scores did not contribute to the impaired sperm morphology observed in AS patients with varicocele. CONCLUSIONS: An increased frequency of varicocele was found in AS patients associated with sperm abnormalities but independent of therapy, anti-sperm antibodies, hormonal alterations, or disease parameters. Investigation for varicocele should be routine in AS patients with fertility problems.

Penile anthropometry in systemic lupus erythematosus patients.

The aim of this study was to evaluate penile anthropometry in systemic lupus erythematosus (SLE) patients compared with healthy controls and the possible relevant pubertal, clinical, hormonal and treatment factors that could influence penile dimensions. Twenty-five consecutive SLE patients were assessed by urological examination, sexual function, testicular ultrasound, hormones, sperm analysis, genetic analysis, clinical features and treatment. The control group included 25 age-matched healthy males. SLE patients had a lower median penis length and circumference [8 (7.5-10) vs. 10 (8-13) cm, p = 0.0001; 8 (7-10) vs. 10 (7-11) cm, p = 0.001; respectively], lower median testicular volume by right and left Prader [15 (10-25) vs. 20 (12-25) ml, p = 0.003; 15 (10-25) vs. 20 (12-25) ml, p = 0.006; respectively], higher median of follicle-stimulating hormone [5.8 (2.1-25) vs. 3.3 (1.9-9) IU/l, p = 0.002] and lower morning total testosterone levels (28% vs. 0%, p = 0.009) compared with controls. In spite of that, erectile dysfunction was not observed in patients or controls. Analyses of lupus patients revealed that the median penis circumference was lower in patients with disease onset before first ejaculation compared with those with disease onset after first ejaculation [7.8 (7-10) vs. 9.0 (7.5-10) cm, p = 0.026]. No differences were observed in the median penile anthropometry regarding sexual dysfunction (p = 0.610), lower morning total testosterone levels (p = 0.662), oligo/azoospermia (p = 0.705), SLE Disease Activity Index ≥ 4 (p = 0.562), Systemic Lupus International Collaborating Clinics/ACR Damage Index ≥ 1 (p = 0.478), prednisone cumulative dose (p = 0.789) and intravenous cyclophosphamide therapy (p = 0.754). Klinefelters syndrome (46XY/47XXY) was diagnosed in one (4%) SLE patient with decreased penile size whereas Y-chromosomal microdeletions was absent in all of them. In conclusion, we have identified reduced penile dimensions in SLE patients with no deleterious effect in erectile function. Disease onset before first ejaculation seems to affect penis development in pre-pubertal lupus.

Treatment of low-flow vascular malformations by ultrasound-guided sclerotherapy with polidocanol foam: 24 cases and literature review.

OBJECTIVES: Treatment by sclerotherapy has been suggested as a first-line treatment of low-flow vascular malformations. This study reports our experience in treating low-flow vascular malformations by ultrasound-guided sclerosis with polidocanol foam at the Vascular Medicine Department in Grenoble, France. DESIGN: Retrospective single-centre consecutive series. MATERIALS AND METHODS: Between January 2006 and December 2009, we analysed the complete records of patients with symptomatic low-flow vascular malformations of venous, lymphatic or complex type (Klippel-Trenaunay syndrome, KTS) treated by ultrasound-guided sclerosis. The therapeutic indication was always validated by the Consultative Committee for vascular malformations of the University Hospital of Grenoble. All vascular malformations were classified according to the Hamburg Classification. The sclerosing agent was polidocanol used as foam. RESULTS: A total of 24 patients between 7 and 78 years were treated (19 venous malformations, three KTSs and two venous-lymphatic malformations). The concentrations of polidocanol used ranged from 0.25% to 3%. The average number of sessions was 2.3 (1-16). After a median follow-up at 5 months after the last session, 23 out of 24 patients reported a decrease in pain; in nine cases (37.5%), over 50% reduction in size was observed, and in 14 cases (58.3%), a reduction of less than 50% of the original size was obtained. Two minor side effects were reported. CONCLUSIONS: Treatment by ultrasound-guided sclerosis using polidocanol foam seems to be well tolerated and can improve the symptoms of low-flow malformations without the risks of more aggressive sclerosing agents, such as ethanol.

Simple PDMS microdevice for biomedical applications.

Polydimethylsiloxane (PDMS) is a well-known biocompatible polymer employed for many applications in the biomedical field. In this study, the biocompatibility and versatility of PDMS was tested setting up a microdevice devoted to the purification and analysis of nucleic acids. The PDMS microdevice was demonstrated to successfully fulfill all requirements of genetic analyses such as genotyping and pathogen DNA identification both in multiplex and real-time PCR, suggesting the possibility to carry out a molecular test directly on-chip. Moreover, the PDMS microdevice was successfully applied to the purification and detection of disease biomarkers, such as microRNAs related to cancer or heart disease. On-chip microRNA purification was demonstrated starting from clinically relevant samples, i.e. plasma, serum, tissue biopsies. Significantly, the purification and the transcription of microRNA into cDNA occur in the same PDMS chamber, saving time and labor for the overall analysis. Again, the PDMS microdevice was confirmed as a notable candidate for compact, rapid, easy-to-use molecular tests.

Testicular Sertoli cell function in male systemic lupus erythematosus.

OBJECTIVE: To assess the testicular Sertoli cell function in male SLE patients. METHODS: Thirty-four consecutive patients were prospectively selected to evaluate serum inhibin B. Clinical features, treatment, semen analysis, urological evaluation, testicular ultrasound, hormones and anti-sperm antibodies were determined. RESULTS: Patients were subdivided into two groups: low serum inhibin B (Group 1, n = 8) and normal levels (Group 2, n = 26). The median sperm concentration (P = 0.024), total sperm count (P = 0.023) and total motile sperm count (P = 0.025) were lower in Group 1. Inhibin B levels were positively correlated with sperm concentration (r = 0.343), total motile sperm count (r = 0.357), and negatively correlated with follicule-stimulating hormone (FSH) (r = 0.699) and luteinizing hormone (r = 0.397). The median serum inhibin B was lower in SLE patients treated with intravenous cyclophosphamide (IVCYC) compared with those without this therapy (P = 0.031). Further evaluation of the 26 SLE patients with normal inhibin B and FSH levels revealed that medians of inhibin B/FSH ratio were lower in SLE patients with oligozoospermia compared with normozoospermia (P = 0.004). This ratio was also lower in SLE patients treated with IVCYC than those without this therapy (P = 0.04). In contrast, inhibin B serum level alone did not discriminate the later group of patients (P = 0.12). CONCLUSIONS: This is the first study to identify a high frequency of testicular Sertoli cell dysfunction in male SLE associated with semen abnormalities. Further prospective studies are necessary to determine if inhibin levels and inhibin B/FSH ratio will be an earlier and useful marker of IVCYC toxicity in these patients.

[Febrile cellulitis surrounding a scar revealing a large immunoblastic B-cell lymphoma]. / Dermohypodermite fébrile péricicatricielle révélatrice d'un lymphome B immunoblastique à grandes cellules.

BACKGROUND: Secondary skin sites of lymphoma appear in the advanced stages of the disease. We report the first case of a pericicatricial skin infiltration, mimicking febrile dermohypodermitis, revealing diffuse immunoblastic large B-cell non-Hodgkin's lymphoma. PATIENTS AND METHODS: Four months after decompressive cervical laminectomy, a 56-year-old man presented an inflammatory pericicatricial patch evoking cellulitis in a setting of hyperthermia and lymphadenopathy. Blood cultures and bacteriological analysis of skin biopsy samples were negative. The images showed infiltration of the soft subcutaneous areas and polyadenopathy. Two weeks later, several subcutaneous nodules appeared on the trunk. Histological analysis and immunolabelling pointed to immunoblastic large B-cell non-Hodgkin's lymphoma. A clone of B lymphocytes CD45+, CD20+, CD79a+, Bcl2+, CD5+, MUM1+, CD3-, CD10-, CD23- and Bcl6- was seen. The remainder of the extension examination was negative. CHOP-rituximab polychemotherapy resulted in complete regression of all lesions, notably the inflammatory cervical plaque. DISCUSSION: Secondary skin manifestations of lymphoma are generally non-specific (pruritus, ichthyosis, purpura, etc.) rather than specific in terms of lymphoid infiltration. As in our patient, certain cutaneous sites of lymphoma may have a misleading clinical presentation, histological analysis alone was able to provide a conclusive diagnosis. In our patient, the highly specific infiltration seen around the entire scar could either suggest a Koebner phenomenon or point to a role of the cutaneous aggression within the development of an inflammatory process contributing to pericicatricial infiltration by lymphoid cells. Locoregional invasion from the osseous part of the cervical spine and not macroscopically diagnosed during neurosurgery could also be responsible.

miRNA purification with an optimized PDMS microdevice: Toward the direct purification of low abundant circulating biomarkers.

A reliable clinical assay based on circulating microRNAs (miRNAs) as biomarkers is highly required. Microdevices offer an attractive solution as a fast and inexpensive way of concentrating these biomarkers from a low sample volume. A previously developed polydimethylsiloxane (PDMS) microdevice able to purify and detect circulating miRNAs was here optimized. The optimization of the morphological and chemical surface properties by nanopatterning and functionalization is presented. Surfaces were firstly characterized by atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), fluorescamine assay and s-SDTB (sulphosuccinimidyl-4-o-(4,4-dimethoxytrityl) butyrate) assay and subsequently tested for their capacity to adsorb a fluorescent miRNA. From our analysis, modification of surface charge with 0.1% APTMS ((3-Aminopropyl)trimethoxysilane) and 0.9% PEG-s (2-[Methoxy-(polyethyleneoxy)propyl]trimethoxysilane) performed at 60°C for 10min was identified as the best purification condition. Our optimized microdevice integrated with real-time PCR detection, was demonstrated to selectively purify both synthetic and natural circulating miRNAs with a sensitivity of 0.01pM.

Serum and peritoneal abnormalities in endometriosis: potential use as diagnostic markers.

Endometriosis is an ambiguous disease and its exact pathogenesis still remains elusive to clinicians and scientists. Local and systemic aberrations in immune response are associated with endometriosis. This article reviews the literature regarding various immunological factors such as cytokines, growth factors, adhesion molecules and angiogenic factors involved in the etiopathogenesis of this disease. Our review summarizes the literature regarding biomarkers, which may be reliable nonsurgical tools used in the diagnosis of endometriosis. Superior biomarkers characterized by high sensitivity, specificity and predictive value can help in the early detection and monitoring of disease progression as well as its response to therapeutic treatments critical for its management. A combination predictive model utilizing multiple biomarkers rather then individual markers alone is proposed to improve the diagnostic performance for identifying women with a high likelihood of having endometriosis. Immunomodulators and angiogenic factor blockers have a potential for endometriosis treatment and also to alleviate the pain or infertility associated with the disease. Potential new therapeutic agents include modulators, such as cytokine receptor blockers and angiogenic receptor blockers, presently used for treating endometriosis.

On-chip purification and detection of hepatitis C virus RNA from human plasma.

Hepatitis C virus (HCV) is one of the main causes of chronic liver disease worldwide. The diagnosis and monitoring of HCV infection is a crucial need in the clinical management. The conventional diagnostic technologies are challenged when trying to address molecular diagnostics, especially because they require a complex and time-consuming sample preparation phase. Here, a new concept based on surface functionalization was applied to viral RNA purification: first of all polydimethylsiloxane (PDMS) flat surfaces were modified to hold RNA adsorption. After a careful chemical and morphological analysis of the modified surfaces, the functionalization protocols giving the best RNA adsorbing surfaces were applied to PDMS microdevices. The functionalized microdevices were then used for RNA purification from HCV infected human plasma samples. RNA purification and RT were successfully performed in the same microdevice chamber, saving time of analysis, reagents, and labor. The PCR protocol for HCV cDNA amplification was also implemented in the microdevice, demonstrating that the entire process of HCV analysis, from plasma to molecular readout, could be performed on-chip. Not only HCV but also other microdevice-based viral RNA detection could therefore result in a successful Point-of-Care (POC) diagnostics for resource-limited settings.

Aicardi syndrome with multiple tumors: a case report with literature review.

A 5-year-old girl with Aicardi syndrome, choroid plexus papilloma and multiple gastric hyperplastic polyps is reported. Gastric polyposis is unusual in the pediatric age group and has not previously been reported in a patient with Aicardi syndrome. A variety of uncommon benign and malignant tumors have been associated with Aicardi syndrome; this literature is briefly reviewed. The increased frequency of tumors in Aicardi syndrome should be kept in mind when evaluating these patients.

[Infantile spasms: clinical course]. / Spasmi infantili: evoluzione clinica.

The authors report on the factor which interferes on follow-up of children affected by infantile spasm. On the basis of their series and on the data of literature the factor more indicative for the clinical evolution are: type and dosage of treatment, onset early or delayed, and the aetiology. While for the first two factors the opinion of the expert are remarkable discordant, there is a general agreement that the evolution of infantile spasm is mainly based on the causes determining such kind of epilepsy.

Diagnosis and classification of autoimmune orchitis.

Autoimmune orchitis is characterized by testis inflammation and the presence of specific antisperm antibodies (ASA). It is classified in two categories. Primary autoimmune orchitis is defined by infertility and asymptomatic orchitis associated with ASA (100%) directed to the basement membrane or seminiferous tubules in infertile men, without any systemic disease and usually asymptomatic. Secondary autoimmune orchitis is characterized by symptomatic orchitis and/or testicular vasculiti`s associated with a systemic autoimmune disease, particularly vasculitis. These patients typically demonstrate testicular pain, erythema and/or swelling. ASA in secondary autoimmune orchitis have been reported in up to 50% of patients, especially in systemic lupus erythematosus patients. The pathogenesis of primary as well as secondary autoimmune orchitis is still unknown. Although the etiology is likely to be multifactorial, testicular inflammation, infection or trauma may induce T cell response with pro-inflammatory cytokine production with a consequent blood-testis-barrier permeability alteration, ASA production and apoptosis of spermatocytes and spermatids. ASA is known to cause immobilization and/or agglutination of spermatozoa, which may block sperm-egg interaction resulting in infertility. Assisted reproduction has been used as an efficient option in primary cases and immunosuppressive therapy for secondary autoimmune orchitis, although there is no double-blind, randomized trial to confirm the efficacy of any treatment regimens for these conditions.

Impact of body mass index, age and varicocele on reproductive hormone profile from elderly men

ABSTRACT Objectives: To study the impact of obesity, age and varicocele on sexual hormones fof adult and elderly men. Materials and Methods: 875 men who were screened for prostate cancer were enrolled in this study. Data recorded comprised age, body mass index (BMI), serum levels of total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and follicular stimulating hormone (FSH). Patients were divided in groups according to their BMI in underweight, normal weight, overweight and obese grades 1, 2 or 3. First, it was studied the association between age, BMI, and hormone profile. Then, clinical varicocele was evaluated in 298 patients to assess its correlation to the others parameters. Results: Obese patients had lower levels of TT, FT and SHBG (p<0.001) compared to underweight or normal weight patients. There were no differences in age (p=0.113), FSH serum levels (p=0.863) and LH serum levels (p=0.218) between obese and non-obese patients. Obese grade 3 had lower levels of TT and FT compared to obese grade 1 and 2 (p<0.05). There was no difference in the SHBG levels (p=0.120) among obese patients. There was no association between varicocele and BMI; and varicocele did not impact on testosterone or SHBG levels. Conclusions: Men with higher BMI have a lower serum level of TT, FT and SHBG. The presence of clinical varicocele as well as its grade has no impact on hormone profile in elderly men.

Minor sperm abnormalities in young male post-pubertal patients with juvenile dermatomyositis.

The objective of the present study was to identify sperm abnormalities in young male patients with juvenile dermatomyositis (JDM). In 2005, 18 male JDM patients, diagnosed according to the criteria of Bohan and Peter, were followed at the Pediatric Rheumatology Unit and Rheumatology Division, of our Institution. Of the 18 males, 11 were pre-pubertal and 7 were post-pubertal. Two of 7 post-pubertal JDM male patients were excluded: one for orchidopexy for cryptorchidism and the other for testicular ectopia in the left testis. The remaining 5 post-pubertal JDM patients were prospectively evaluated on the basis of two semen analyses, according to the World Health Organization (WHO), urologic evaluation, testicular Doppler ultrasound hormone profile. The data of the JDM patients were compared with those of 5 age-matched healthy controls. The median age 18, was similar in JDM patients and controls. All JDM patients had teratozoospermia (abnormal sperm morphology), as did 4 (80%) of the controls. One of JDM patients had previous oligoasthenoteratozoospermia treated with intravenous cyclophosphamide with normalization of the number and concentration of the sperm after 5 years. All sperm parameters (sperm concentration, total sperm count and total motile sperm count by WHO, and sperm morphology by Kruger strict criteria), testicular volumes by Prader orchidometer and ultrasound, and hormones were similar in JDM patients compared with controls. The frequency of anti-sperm antibodies was similar in both groups. All JDM patients had minor sperm abnormalities in the head, midpiece, and/or tail of spermatozoids. Serial semen analyses in larger study populations are necessary to identify the extent and duration of sperm abnormalities in male patients with idiopathic inflammatory myopathies.