The first-generation phosphodiesterase 5 inhibitors and their pharmacokinetic issue.

BACKGROUND: Erectile dysfunction (ED) is a relatively frequent disease that negatively impacts the overall quality of life, well-being, and relationships. Although the use of phosphodiesterase 5 inhibitors (PDE5is) has revolutionized the treatment of ED, a high percentage of ED patients discontinue PDE5i treatment. OBJECTIVES: (i) To analyze the reasons for patient dissatisfaction leading to PDE5i discontinuation; (ii) analyze the pharmacokinetics of new formulations focusing on the time needed to reach an effective plasma concentration of PDE5is (Tonset ) following drug intake; and (iii) summarize the physicochemical properties of sildenafil to understand which excipients may increase the absorption rate. MATERIAL AND METHODS: An online PubMed literature search was conducted to identify English language publications from inception to January 2019. RESULTS: The main reasons for patient dissatisfaction when using PDE5is on demand are the relatively long Tonset after taking vardenafil and sildenafil, including formulations such as film-coated tablets, fine granules, orally disintegrating tablets (ODTs), and oral thin films (ODFs). The relatively long Tonset , further worsened when accompanied by eating, highlights the following: (i) the need for planning intercourse, determining partner-related issues; (ii) issues when having sex before the maximum effect of the drug; and (iii) lower drug-related placebo effects. Some data suggest that sildenafil is a 'difficult' molecule, but Tonset can be improved following absorption by buccal mucosa using appropriate excipients. CONCLUSIONS: We conclude that several ODT and ODF formulations can improve the 'discretion' issue because they are taken without water, but they have similar pharmacokinetics to corresponding film-coated tablet formulations. One ODF formulation of sildenafil was characterized by a shorter Tonset and could potentially increase patient satisfaction following treatment. However, more clinical studies are needed to confirm the findings. Surfactants and ascorbic acid appear to be crucial excipients for achieving a high absorption rate, but more studies are needed.

Guía clínica de la Asociación Europea de Urología sobre la vasectomía / European Association of Urology Guidelines on Vasectomy

Contexto: La Asociación Europea de Urología presenta su guía clínica para la vasectomía. La vasectomía es muy eficaz, pero pueden surgir problemas que están relacionados con la falta de información preoperatoria del paciente, el procedimiento quirúrgico y el seguimiento postoperatorio. Objetivo: Esta guía clínica tiene por objeto proporcionar información y recomendaciones para los médicos que realizan vasectomías y promover el suministro de información adecuada al paciente antes de la operación para evitar expectativas poco realistas y procedimientos legales. Adquisición de la evidencia: Se llevó a cabo una revisión exhaustiva de la literatura mediante Medline, Embase y la Base de Datos Cochrane de Revisiones Sistemáticas de 1980 a 2010. La atención se centró en los ensayos controlados aleatorizados (ECA) y los metaanálisis de los ECA (nivel 1 de evidencia) y en los estudios bien diseñados sin aleatorización (nivel 2 y 3 de evidencia). Un total de 113 registros únicos fueron identificados para su consideración. Se excluyeron las publicaciones que no estaban en lengua inglesa, así como los estudios publicados como resúmenes solamente o informes de las reuniones. Síntesis de la evidencia: La guía clínica debate las indicaciones y contraindicaciones de la vasectomía, la información y el asesoramiento preoperatorio del paciente, las técnicas quirúrgicas, los cuidados postoperatorios y el posterior análisis del semen y las complicaciones y consecuencias finales. Conclusiones: La vasectomía tiene la intención de ser un método anticonceptivo permanente; No hay contraindicaciones absolutas para la misma. Las contraindicaciones relativas pueden ser la ausencia de hijos, edad < 30 años, una enfermedad grave, ninguna relación actual y dolor en el escroto. El asesoramiento preoperatorio debe incluir métodos alternativos de anticoncepción, tasas de complicación y fracaso y la necesidad de análisis del semen postoperatorio. Se debe obtener consentimiento informado antes de la operación. Aunque el uso de cauterio de la mucosa y la interposición fascial han demostrado reducir el fracaso temprano en comparación con la ligadura simple y resección de un segmento de vaso pequeño, no hay datos sólidos que muestren que una técnica de vasectomía en particular es superior en cuanto a prevención de la recanalización tardía y espontánea del embarazo después de la vasectomía. Tras el análisis del semen se puede dar el alta en caso de azoospermia documentada y en el caso de espermatozoides inmóviles en la eyaculación por lo menos 3 meses después del procedimiento (AU)

Context: The European Association of Urology presents its guidelines for vasectomy. Vasectomy is highly effective, but problems can arise that are related to insufficient preoperative patient information, the surgical procedure, and postoperative follow-up. Objective: These guidelines aim to provide information and recommendations for physicians who perform vasectomies and to promote the provision of adequate information to the patient before the operation to prevent unrealistic expectations and legal procedures. Evidence acquisition: An extensive review of the literature was carried out using Medline, Embase, and the Cochrane Database of Systematic Reviews from 1980 to 2010. The focus was on randomised controlled trials (RCTs) and meta-analyses of RCTs (level 1 evidence) and onwell-designed studies without randomisation (level 2 and 3 evidence). A total of 113 unique records were identified for consideration. Non-English language publications were excluded as well as studies published as abstracts only or reports from meetings. Evidence synthesis: The guidelines discuss indications and contraindications for vasectomy, preoperative patient information and counselling, surgical techniques, postoperative care and subsequent semen analysis, and complications and late consequences. Conclusions: Vasectomy is intended to be a permanent form of contraception. There are no absolute contraindications for vasectomy. Relative contraindications may be the absence of children, age < 30 yr, severe illness, no current relationship, and scrotal pain. Preoperative counselling should include alternative methods of contraception, complication and failure rates, and the need for postoperative semen analysis. Informed consent should be obtained before the operation. Although the use of mucosal cautery and fascial interposition have been shown to reduce early failure compared to simple ligation and excision of a small vas segment, no robust data show that a particular vasectomy technique is superior in terms of prevention of late recanalisation and spontaneous pregnancy after vasectomy. After semen analysis, clearance can be given in case of documented azoospermia and in case of rare non motile spermatozoa in the ejaculate at least 3 mo after the procedure (AU)

[European Association of Urology guidelines on vasectomy]. / Guía clínica de la Asociación Europea de Urología sobre la vasectomía.

CONTEXT: The European Association of Urology presents its guidelines for vasectomy. Vasectomy is highly effective, but problems can arise that are related to insufficient preoperative patient information, the surgical procedure, and postoperative follow-up. OBJECTIVE: These guidelines aim to provide information and recommendations for physicians who perform vasectomies and to promote the provision of adequate information to the patient before the operation to prevent unrealistic expectations and legal procedures. EVIDENCE ACQUISITION: An extensive review of the literature was carried out using Medline, Embase, and the Cochrane Database of Systematic Reviews from 1980 to 2010. The focus was on randomised controlled trials (RCTs) and meta-analyses of RCTs (level 1 evidence) and on well-designed studies without randomisation (level 2 and 3 evidence). A total of 113 unique records were identified for consideration. Non-English language publications were excluded as well as studies published as abstracts only or reports from meetings. EVIDENCE SYNTHESIS: The guidelines discuss indications and contraindications for vasectomy, preoperative patient information and counselling, surgical techniques, postoperative care and subsequent semen analysis, and complications and late consequences. CONCLUSIONS: Vasectomy is intended to be a permanent form of contraception. There are no absolute contraindications for vasectomy. Relative contraindications may be the absence of children, age <30 yr, severe illness, no current relationship, and scrotal pain. Preoperative counselling should include alternative methods of contraception, complication and failure rates, and the need for postoperative semen analysis. Informed consent should be obtained before the operation. Although the use of mucosal cautery and fascial interposition have been shown to reduce early failure compared to simple ligation and excision of a small vas segment, no robust data show that a particular vasectomy technique is superior in terms of prevention of late recanalisation and spontaneous pregnancy after vasectomy. After semen analysis, clearance can be given in case of documented azoospermia and in case of rare nonmotile spermatozoa in the ejaculate at least 3 mo after the procedure.

Role of granulocyte elastase and interleukin-6 in the diagnosis of male genital tract inflammation.

Chronic genital tract inflammations are a frequent cause or at least a concomitant factor of male fertility disturbances. The diagnosis is difficult because of the mostly asymptomatic course of the disease. Therefore, determination of biochemical markers of inflammation in addition to the number of leucocytes in the seminal plasma has been recommended. The aim of the study was to find out whether determination of granulocyte elastase and interleukin-6 provide comparable and reliable results with regard to diagnosis of genital tract inflammation; in addition, the association between genital tract inflammation and semen quality should be evaluated with special focus on potentially disturbed sperm functions like sperm motility and DNA integrity. In a prospective study, the concentrations of interleukin-6 (IL-6) and granulocyte elastase were determined in seminal plasma samples from 340 patients to investigate the relationship with other parameters of genital tract inflammation such as the number of peroxidase-positive cells and conventional semen parameters. Microbiological investigations were included. As post-testicular inflammatory influences may cause sperm DNA damage, the correlation between IL-6 and elastase and DNA integrity was evaluated by the sperm chromatin structure assay. IL-6 and elastase were significantly correlated both with each other (P < 0.01) and the number of peroxidase-positive cells (P < 0.01). IL-6 showed a highly significant negative correlation with sperm vitality (P < 0.01) and a significant negative correlation with sperm motility (P < 0.05). Elastase concentrations were highly significantly associated with the number of peroxidase-positive cells (P < 0.01) and negatively correlated with sperm vitality (P < 0.01). Moreover, there were significantly negative correlations with sperm motility (P < 0.05), progressive motility according to WHO a quality (P < 0.05) as well as sperm morphology (P < 0.05). In addition, a significant negative correlation was observed between elastase concentrations and percentage of spermatozoa with intact DNA, which may suggest the use of anti-inflammatory treatment. It can be concluded that both IL-6 and granulocyte elastase are useful and suitable as markers for silent genital tract inflammation; in contrast to previous contributions there were clear correlations of IL-6 and granulocyte elastase with sperm parameters, the relationship of elastase with semen quality being more marked. Moreover, the results of the study confirm the need for a change of the threshold value of peroxidase-positive cells according to WHO definition to lower levels for definition of silent genital tract inflammation.

Aetiology of haemospermia.

There are several unknown factors which cause haemospermia. An earlier developed diagnostic scheme has been expended by novel imaging techniques and biopsy methods. A detailed case history, physical examination and microscopic analysis of the ejaculate is required. In haemo-pyospermia a complete microbiological analysis must be escalated. Noninvasive imaging techniques (ultrasound, computer tomography and magnetic resonance imaging) help in detecting calculous and malignant diseases. So far, as a precise diagnosis has not been available, urethroscopy has been performed. Malignancies (prostate, seminal vesicles) must be histologically verified by biopsies. In contempt of our efforts the practice shows a part of haemospermia remaining essential. Analysing two time periods we found prostatic calculi, chronic prostatitis and carcinoma of the prostate unequivocally as most frequent causes. Considering the rare genital malignancies we find more than 10% frequency. Notably, in our study only 2.4% of the malignancies occurred in patients under 40 years of age. Hence a detailed diagnosis is advocated in haemospermia patients over 40 years. Finally, we may state that in contempt of the applied modern imaging techniques 15% of patients with haemospermia had unknown aetiology.

Non-surgical treatment of erectile dysfunction.

Authors survey the conservative treatment possibilities of erectile dysfunction. With the increase in interest, they estimate the new oral- and intracavernosal drugs, giving a review of their experiences with the treatment. A perspective prognosis is given of the important role of NO (nitric oxide) donors and PHD (phosphodiesterase) inhibitor drugs in the field of conservative therapy, while intracavernosal and intraurethral prostaglandin therapies are still important ingredients in the therapeutic arsenal, as is hormone substitution in indicated cases.

Testicular sperm aspiration (first Hungarian results).

Authors summarize the first results with the use of spermatozoas retrieved with direct surgical method in intracytoplasmic injection in Hungary (1995-1997). Eighty-nine procedures were performed in 65 patients and 84 cases were successful. Out of 84 cases 23 clinical pregnancies could be achieved (27.3%). Thirteen children were born, including one case of twins and one triplets.

Retractorscopic nephrectomy: initial report.

The authors describe a newly developed minimal access method for nephrectomy. The mini approach-a 5 cm skin incision-can be performed with a special retractorscope, which is an open lumen "scope" with fiberoptic light system.

Treatment for potency problems with Afrodor 2000.

The andrological role of the drug Afrodor 2000 (a special mixture of sedatives, aphrodisiacs and vitamin E) in patients with erectile dysfunction is discussed. In the conservative treatment of erectile dysfunction the aphrodisiacs and severe medicine mixtures are widely used. To our practice one of the most useful drugs is Afrodor 2000, mainly for the erectile dysfunction patients of psychological origin.

Bladder augmentation with detubularized intestinal segment.

The authors report on 9 cases of bladder augmentation with detubularized intestinal segments. The capacity of the contracted bladder was increased in 4 cases; care was taken to prevent the development of an hour-glass bladder. In a young female patient a caecal-ileal segment was applied so that in case of a possible future pregnancy the mesentery should not hinder the growth of the uterus. In 4 cases hypertonic neurogenic bladders were augmented with intestinal segments, thus the further destruction of the kidneys could be avoided. In one case the reflux was hindered by a Kock valve, but stagnation developed above the valve, therefore it was eliminated and replaced by a 15 cm intestinal segment. In one case the uninhibited neurogenic bladder was augmented, the resistance of the urethra increased as a result of which the patient stayed dry between self-catheterizations. Attention is called upon the metabolic disturbances and increased risk of infection following intestinal implantations.

Our experience with testicular prosthesis implantation.

The authors survey the history of the testicular prosthesis implantations in Hungary. They summarize their experiences in the mirror of the results of their own cases. Authors establish that this operative procedure is very important for the young patients to the regeneration of the esthetic role of the testes, prevent the psychogenous complications, and set up again the so-called "man symbol function".

Surgical male contraception.

After giving a short account on the possible ways of male contraception, the authors outline the administration of surgical sterilization and its professional follow-up based on their own experience. Their suggestions concerning legal regulations aim, on the one hand, at the extension of the topic, on the other hand at supporting the specialists interested in surgical contraception.

Successful treatment of erectile disfunction with Fortisex coated tablets.

After a brief survey of treatment, possibilities of erectile dysfunction, the Authors describe their results with FORTISEX coated tablets playing an important role in the conservative therapy even in our days. Their results suggest that the primary advantage of the product appears in increasing the libido in sexual problems of psychic origin, but its secondary field of application is the minor improvement of erectile parameters of disfunctions of "mixed" history.

Vacuum therapy in the treatment of erectal impotence.

The authors were the first in Hungary to use vacuum-induced erection in the treatment of erectal dysfunction. Negative pressure was induced by OSBON ERECAID SYSTEM. Erectal impotence was successfully treated with this non-invasive and complications-free method in patients with diabetes and psychic problems. The method was applied first for ameliorating sexual complaints due to virile climacteric and--based on the results--its application is recommended.