An online Sexual Health and Rehabilitation eClinic (TrueNTH SHAReClinic) for prostate cancer patients: a feasibility study.

PURPOSE: The primary objective was to determine the feasibility of implementing the TrueNTH SHAReClinic as a pan-Canadian sexual health and rehabilitation intervention for patients treated for localized prostate cancer. METHODS: The feasibility study was designed to evaluate the accessibility and acceptability of the intervention. Participants from five institutions across Canada were enrolled to attend one pre-treatment and five follow-up online clinic visits over 1 year following their prostate cancer (PC) treatment. RESULTS: Sixty-five patients were enrolled in the intervention. Website analytics revealed that 71% completed the intervention in its entirety, including the educational modules, with an additional 10% completing more than half of the intervention. Five thousand eighty-three views of the educational modules were made along with 654 views of the health library items. Over 1500 messages were exchanged between participants and their sexual health coaches. At 12 months, the intervention received an overall average participant rating of 4.1 out of 5 on a single item satisfaction measure. CONCLUSION: Results support the TrueNTH SHAReClinic as highly acceptable to participants as defined by intervention adherence and engagement. The TrueNTH SHAReClinic demonstrated promise for being a feasible and potentially resource-efficient approach to effectively improving the sexual well-being of patients after PC treatment.

Recommendations for the classification of diseases as CFTR-related disorders.

Several diseases have been clinically or genetically related to cystic fibrosis (CF), but a consensus definition is lacking. Here, we present a proposal for consensus guidelines on cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (CFTR-RDs), reached after expert discussion and two dedicated workshops. A CFTR-RD may be defined as "a clinical entity associated with CFTR dysfunction that does not fulfil diagnostic criteria for CF". The utility of sweat testing, mutation analysis, nasal potential difference, and/or intestinal current measurement for the differential diagnosis of CF and CFTR-RD is discussed. Algorithms which use genetic and functional diagnostic tests to distinguish CF and CFTR-RDs are presented. According to present knowledge, congenital bilateral absence of vas deferens (CBAVD), acute recurrent or chronic pancreatitis and disseminated bronchiectasis, all with CFTR dysfunction, are CFTR-RDs.

An obstetric patient with neurocadiogenic syncope.

We report the peripartum management of a 29-year-old primigravid patient with neurocardiogenic syncope, which had been diagnosed six years previously on tilt-table testing. General principles were applied to minimise the risk of precipitating syncopal episodes. She had an uneventful ventouse-assisted vaginal delivery under epidural anaesthesia in our obstetric high dependency unit. The optimum management of these patients has yet to be established.

Transcranial Doppler ultrasonography-directed intravenous glycoprotein IIb/IIIa receptor antagonist therapy to control transient cerebral microemboli before and after carotid endarterectomy.

BACKGROUND: Patients with a transient focal neurological deficit, critical carotid stenosis and/or microemboli detected by transcranial Doppler ultrasonography (TCD) have a significant risk of stroke. The effect of tirofiban, a selective glycoprotein IIb/IIIa inhibitor, was assessed in patients with microembolic signals on TCD after transient ischaemic attacks or carotid endarterectomy (CEA). METHODS: Thirty-three patients with microemboli on TCD (13 symptomatic preoperative, 19 postoperative, one both) were treated with tirofiban between 2002 and 2007. All patients had carotid stenosis greater than 70 per cent. TCD monitoring was used during and after tirofiban therapy. RESULTS: The median (range) rate of microemboli decreased from 22 (4-260) per h before surgery and 81 (44-216) per h after surgery to 0 (0-9) per h in both groups (P < 0.001, Mann-Whitney U test). This occurred rapidly (preoperative median 30 min; postoperative median 45 min) and was well tolerated in all patients, with no serious adverse effects. CONCLUSION: Cerebral microemboli were controlled by tirofiban both before and after CEA. Further study is required to compare the relative efficacy of tirofiban and dextran.

Quality of life post radical prostatectomy: a male perspective.

The purpose of this qualitative study was to explore the meaning and effect of urinary incontinence and impotence on the quality of life for men with prostate cancer. The Cancer Recovery Model guided the study. This model is based on the assumption that the chronicity of cancer is a function of recovery as well as illness and focuses on the strength of an individual to regain his powers of survival until death. The study identified indicators for quality of life for men who have had a radical prostatectomy for cancer that should be included in developing discharge teaching plans and reinforced in community followup.

Varicocele is associated with abnormal retention of cytoplasmic droplets by human spermatozoa.

OBJECTIVE: To determine whether varicocele is associated with retention of sperm cytoplasmic droplets in infertile men. DESIGN: Retrospective study. SETTING: University infertility clinic. PATIENT(S): Nonazoospermic men with idiopathic (n = 69) and varicocele-associated infertility (n = 73), and 20 fertile controls presenting for vasectomy. INTERVENTION(S): None. MAIN OUTCOME MEASURES(S): Standard semen parameters and percentage of spermatozoa with cytoplasmic droplets on Papanicolaou smears. RESULT(S): No statistically significant differences were found between the fertile and infertile groups with respect to semen volume. Fertile controls had significantly greater mean percent sperm motility and normal morphology than infertile men. The mean percentage of sperm with residual cytoplasm was statistically significantly different in all three groups. Infertile men with varicocele had the highest percentage of sperm with cytoplasmic droplets, the next highest level being in men with idiopathic infertility and the lowest level in fertile controls (11.7 +/- 1.0, 8.1 +/- 0.9 and 3.2 +/- 0.4%, respectively, P<.0001). CONCLUSION(S): Our data show that idiopathic and even moreso, varicocele-related male infertility are conditions associated with impaired disposal of residual sperm cytoplasm by the testis and/or epididymis. These data provide a possible mechanism for the observed semen abnormalities and reduced fertility potential associated with varicocele and idiopathic male infertility.

Smoking is associated with the retention of cytoplasm by human spermatozoa.

OBJECTIVES: To determine whether cigarette smoking is associated with the abnormal retention of residual sperm cytoplasm in infertile men. METHODS: Semen samples were obtained from 87 consecutive non-azoospermic men with idiopathic infertility (18 smokers and 69 nonsmokers) and from 20 men presenting for vasectomy (fertile controls). Standard semen parameters and the percentage of spermatozoa with residual cytoplasm (on Papanicolaou smears) were recorded. RESULTS: Subject age, semen volume, and sperm density, motility, and morphology were not significantly different between the two groups of infertile men. However, a significant difference was found in the mean +/- SEM percentages of sperm with cytoplasm droplets between smokers and nonsmokers (12.9% +/- 1.7% and 8.1% +/- 0.9%, respectively; P < 0.001). CONCLUSIONS: Our data suggest that cigarette smoking is associated with retention of sperm cytoplasmic droplets in infertile men, a morphologic characteristic associated with impaired sperm function.

Cystic fibrosis gene mutations and infertile men with primary testicular failure.

It has been proposed that the gene responsible for cystic fibrosis, called the cystic fibrosis transmembrane conductance regulator (CFTR) gene, may play an important role in the process of spermatogenesis. A group of azoospermic men with primary testicular failure underwent CFTR mutation analysis, including assessment of the intron 8 polythymidine tract (IVS8-T tract). An association was not found between CFTR mutations or the 5T variant of the IVS8-T tract and the primary testicular failure phenotype. This finding suggests that CFTR does not play a significant role in the aetiopathogenesis of primary spermatogenic dysfunction. Therefore, the abnormal testicular histological findings in some post-pubertal men with cystic fibrosis may be a result of nutritional deficiency or testicular obstruction rather than a primary defect in spermatogenesis. In addition, the decreased sperm count in oligozoospermic men with CFTR mutations may be secondary to partial reproductive tract obstruction and not abnormal spermatogenesis. Lastly, routine screening of men with primary testicular failure for CFTR gene mutations is not warranted.

Behind the scenes: partners' perceptions of quality of life post radical prostatectomy.

The purpose of this study was to determine the effects of the experience of a radical prostatectomy on the partners of men with prostate cancer. The women described the effects of the experience on their lives and on their partner's life. Descriptions included how they were informed of their partner's diagnosis, emotions at the time of the initial diagnosis, and the sources of information and the decision process that they and their partners used that lead to surgery. The effect of the experience on their quality of life including interpersonal and sexual relationships with their partner and the information that was needed to facilitate self-care after surgery were described. The women provided clear directions for improving the health care system in managing the cancer experience using a family-centered approach.

Effect of varicocelectomy on the abnormal retention of residual cytoplasm by human spermatozoa.

Abnormal retention of cytoplasmic residues by human spermatozoa is associated with the generation of reactive oxygen species (ROS) in semen and defective sperm function. We have examined the effect of varicocelectomy on the retention of residual cytoplasm by human spermatozoa. Clinical reports of 43 men who underwent microsurgical varicocelectomy at our institution during a 1 year period beginning July 1996 were reviewed. Standard semen parameters (concentration, motility and morphology) and residual cytoplasm retention (monitored by Papanicolaou stain) were assessed before and 6 months after varicocelectomy. The percentage of spermatozoa with residual cytoplasm decreased significantly following varicocelectomy compared to pre-operatively (25.8 versus 18.1% respectively). The percentages of motile spermatozoa and normal forms increased significantly (P = 0.0003, P = 0.005 respectively) following varicocelectomy (22.6 versus 32.9% and 46.4 versus 54.4% respectively). Our data suggest that varicocelectomy can improve the disposal of residual sperm cytoplasm by the testis and/or epididymis in infertile men with varicocele. These data also suggest that varicocelectomy reduces the potential for ROS generation by human spermatozoa in these men.

Proportion of cystic fibrosis gene mutations not detected by routine testing in men with obstructive azoospermia.

CONTEXT: Infertile men with obstructive azoospermia may have mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, many of which are rare in classic cystic fibrosis and not evaluated in most routine mutation screening. OBJECTIVE: To assess how often CFTR mutations or sequence alterations undetected by routine screening are detected with more extensive screening in obstructive azoospermia. DESIGN: Routine screening for the 31 most common CFTR mutations associated with the CF phenotype in white populations, testing for the 5-thymidine variant of the polythymidine tract of intron 8 (IVS8-5T) by allele-specific oligonucleotide hybridization, and screening of all exons through multiplex heteroduplex shift analysis followed by direct DNA sequencing. SETTING: Male infertility clinic of a Canadian university-affiliated hospital. SUBJECTS: Of 198 men with obstructive (n = 149) or nonobstructive (n = 49; control group) azoospermia, 64 had congenital bilateral absence of the vas deferens (CBAVD), 10 had congenital unilateral absence of the vas deferens (CUAVD), and 75 had epididymal obstruction (56/75 were idiopathic). MAIN OUTCOME MEASURE: Frequency of mutations found by routine and nonroutine tests in men with obstructive vs nonobstructive azoospermia. RESULTS: Frequency of mutations and the IVS8-5T variant in the nonobstructive azoospermia group (controls) (2% and 5.1% allele frequency, respectively) did not differ significantly from that in the general population (2% and 5.2%, respectively). In the CBAVD group, 72 mutations were found by DNA sequencing and IVS8-5T testing (47 and 25, respectively; P<.001 and P = .002 vs controls) vs 39 by the routine panel (P<.001 vs controls). In the idiopathic epididymal obstruction group, 24 mutations were found by DNA sequencing and IVS8-5T testing (12 each; P=.01 and P=.14 vs controls) vs 5 by the routine panel (P=.33 vs controls). In the CUAVD group, 2 mutations were found by routine testing (P=.07 vs controls) vs 4 (2 each, respectively; P=.07 and P=.40 vs controls) by DNA sequencing and IVS8-5T testing. The routine panel did not identify 33 (46%) of 72, 2 (50%) of 4, and 19 (79%) of 24 detectable CFTR mutations and IVS8-5T in the CBAVD, CUAVD, and idiopathic epididymal obstruction groups, respectively. CONCLUSIONS: Routine testing for CFTR mutations may miss mild or rare gene alterations. The barrier to conception for men with obstructive infertility has been overcome by assisted reproductive technologies, thus raising the concern of iatrogenically transmitting pathogenic CFTR mutations to the progeny.

Seminal plasma biochemical markers and their association with semen analysis findings.

OBJECTIVES: To examine the clinical value of six seminal plasma components in the evaluation of sperm quality and in the differential diagnosis of men with infertility. METHODS: We analyzed 202 seminal plasmas for prostate-specific antigen, glucose, pepsinogen C, insulin-like growth factor binding protein-3, prostaglandin D synthase (PGDS), and BRCA1-like immunoreactive protein (BRCA1-LIP) using quantitative immunofluorometric procedures. The semen donors were categorized in four clinical groups: normal, oligospermic, azoospermic, and vasectomy patients. We then evaluated whether any of these biochemical markers were associated with other parameters of sperm quality, including patient age, total cell concentration, percentage of motility, and percentage of normal morphology. RESULTS: We found that only PGDS concentration was significantly associated with other parameters of sperm quality. PGDS concentration correlated positively with total cell concentration (r = 0.55), percentage of motility (r = 0.31), and percentage of normal morphology (r = 0.31). Median PGDS concentration in seminal plasma decreased progressively from normal to oligospermic to azoospermic to vasectomy patients (P <0.001). There was no overlap between seminal plasma PGDS concentration of normal subjects versus vasectomy patients. The only other parameter that was moderately decreased in vasectomy patients was BRCA1-LIP. The source of PGDS in seminal plasma was determined with various techniques, including immunohistochemistry. This protein is produced and secreted by the Sertoli cells. CONCLUSIONS: Our findings suggest that PGDS concentration in seminal plasma correlates with other known indicators of semen quality and is a new marker of post-testicular obstruction. This biochemical parameter could be used to aid in the differential diagnosis of obstructive and nonobstructive azoospermia in men with infertility.

Heterogeneity of reproductive tract abnormalities in men with absence of the vas deferens: role of cystic fibrosis transmembrane conductance regulator gene mutations.

OBJECTIVE: To determine if the types of reproductive tract abnormalities linked to absence of the vas deferens varies with the cystic fibrosis transmembrane conductance regulator (CFTR) genotype. DESIGN: Prospective data gathering. SETTING: University infertility clinic. PATIENT(S): Forty-six infertile men with absence of the scrotal vas deferens and no signs of cystic fibrosis. INTERVENTION(S): All had blood taken for CFTR gene analysis, 33 had scrotal ultrasounds, and 25 had transrectal ultrasounds. MAIN OUTCOME MEASURE(S): The frequency of testicular, seminal vesicle, and ampullae of the vas deferens malformations was compared between subgroups of men with two, one, or no CFTR gene mutations. RESULT(S): None (0 of 21) of the men with at least one CFTR gene mutations had normal ampullae of the vas or seminal vesicles bilaterally. Two (50%) of 4 men with no CFTR gene mutations had normal ampullae of the vas deferens bilaterally, and 50% had normal bilateral seminal vesicles (statistically significantly different). There was no correlation between testicular malformations and CFTR genotype. CONCLUSION(S): This study indicates that the severity of the malformations in the testis is unrelated to the CFTR genotype, whereas the frequency and severity of wolffian duct malformations are related directly to the CFTR genotype.

Adverse effects on vasoepididymostomy outcomes for men with concomitant abnormalities in the prostate and seminal vesicle.

PURPOSE: Following microsurgical vasoepididymostomy as many as 85% of men have sperm in the ejaculate, yet only 30 to 50% will spontaneously father children. We examined the possibility that there may be concomitant abnormalities in the prostate and seminal vesicle, which may be associated with low pregnancy rates. MATERIALS AND METHODS: Transrectal ultrasound was performed in azoospermic men with suspected epididymal obstruction, excluding those who had undergone vasectomy, to identify abnormalities of the seminal vesicles and ejaculatory ducts. Microsurgical vasoepididymostomy was attempted in all men. RESULTS: Transrectal ultrasound revealed ejaculatory duct dilatation in 13 of 40 men (33%), although only 3 had accompanying seminal vesicle dilatation. Two men had atrophic seminal vesicles with normal ejaculatory ducts. At surgery 8 of 40 patients (20%) were deemed to have irreparable conditions. For the 27 men followed at least 6 months postoperatively patency and pregnancy rates were 75 and 22%, respectively. Mean sperm counts plus or minus standard deviation were significantly higher in men without compared to those with seminal vesicle or ejaculatory duct abnormalities (43 +/- 68 versus 5.7 +/- 6.9 x 10(6) sperm per ml., respectively), and so was the percentage of motile sperm (30 +/- 16% versus 1.2 +/- 2.2%, respectively). Pregnancy rates were also higher in men without (6 of 19, 32%) than with (0 of 8, 0%) seminal vesicle or ejaculatory duct abnormalities. CONCLUSIONS: Transrectal ultrasound detected abnormalities of the seminal vesicles and ejaculatory ducts are common in men with suspected epididymal obstruction. These abnormalities are associated with a poor outcome for vasoepididymostomy. We recommend that all men with suspected epididymal obstruction undergo transrectal ultrasound before any attempted reconstruction.

Outcome of microsurgical reconstruction in men with suspected epididymal obstruction.

PURPOSE: Approximately 3 to 6% of all men presenting with infertility (excluding those with a history of vasectomy) are suspected of having epididymal obstruction. However, other anatomical abnormalities within the male reproductive tract are often encountered. In this study we attempted to define the range and frequencies of anatomical abnormalities in the reproductive tract and the outcome of surgical reconstruction in men with suspected epididymal obstruction and no history of vasectomy. MATERIALS AND METHODS: Between July 1992 and July 1996, 80 azoospermic men with suspected epididymal obstruction underwent scrotal exploration. The anatomical findings and outcomes of reconstructive surgery were reviewed. RESULTS: Of a possible 160 reproductive tract units (2 per patient) we thoroughly examined 147 with suspected epididymal obstruction. Epididymal obstruction was found in 52.7% of the cases with other anatomical abnormalities accounting for the remaining 47.3%. Of the patients 49 (61%) had sperm identified in the epididymis on at least 1 side and underwent vasoepididymostomy, and 3 (4%) had sperm unilaterally in the proximal vas but had ipsilateral distal vasal obstruction. These 3 men underwent crossed vasovasostomy. We were more likely able to perform reconstruction in men whose obstruction was due to an infectious etiology (13 of 14, 93%) compared to either a surgical (5 of 7, 71%) or idiopathic (34 of 59, 58%) etiology. In 28 patients (35%) no sperm was identified in the epididymis or they had no other abnormalities that precluded successful reconstruction on either side. Of those patients who underwent vasoepididymostomy for epididymal obstruction 61% had sperm in the ejaculate postoperatively. CONCLUSIONS: In nearly half the men with suspected epididymal obstruction other reproductive tract abnormalities were detected, most of which precluded successful vasoepididymostomy. Other reproductive tract abnormalities are much less likely to be found, and the outcomes of reconstruction are better if the cause of the obstruction is infectious compared to surgical or idiopathic.

Detection of eubacteria in interstitial cystitis by 16S rDNA amplification.

OBJECTIVE: To determine what role non-culturable microorganisms play in the etiology of interstitial cystitis (IC). MATERIALS AND METHODS: Thirty patients fulfilling NIH criteria for the diagnosis of interstitial cystitis and sixteen control patients with culture negative urine gave written informed consent and underwent bladder biopsy. Polymerase chain reaction (PCR) using two sets of universal primers for bacterial 16S rDNA was performed on urine from the cystoscope and on a cold cup bladder biopsy specimen. Of the PCR positive bladder biopsies, three patients with interstitial cystitis and three controls were randomly selected and cloned. Ten clones from each were sequenced and putative taxonomic assignments made. RESULTS: 12/26 (46%) IC and 5/12 (42%) control urine specimens and 16/30 (53%) and 9/15 (60%) bladder biopsies were PCR positive, respectively. The bacterial populations in the two patient groups tested appeared to be different based upon analysis of the 16S rRNA sequences. CONCLUSIONS: Both IC and control patients had non-culturable bacteria in their bladders. A random sampling of the two populations revealed that the bacterial populations are different, suggesting a possible link between one or more bacterial species and IC.

Higher proportion of intact exon 9 CFTR mRNA in nasal epithelium compared with vas deferens.

The 5-thymidine (5T) variant of the cystic fibrosis transmembrane conductance regulator (CFTR) intron 8 polypyrimidine tract (IVS8-T tract) is the most frequent CFTR gene alteration identified in men with congenital bilateral absence of vas deferens (CBAVD). This alternative splicing variant gives rise to two transcripts, one normal with exon 9 intact and the other with in-frame deletion of exon 9. That CBAVD men usually have none of the other clinical signs of classical cystic fibrosis (CF) suggests less functional CFTR is produced in the reproductive tract than in other CF-associated organs. Nasal epithelia and segments of vas deferens were obtained from healthy, previously vasectomized men who presented for vasectomy reversal. Quantitative RT-PCR was performed on these specimens, with the region of CFTR cDNA spanning exon 9 amplified. For both nasal and vasal tissues, a strong positive correlation was found between the length of the IVS8-T tract and the proportion of mRNA with exon 9 intact. In addition, within the same subject, a significantly higher level of transcripts lacking exon 9 was found in vas deferens than nasal epithelia, regardless of the IVS8-T genotype. These findings suggest that the splicing of CFTR precursor mRNA is less efficient in vasal epithelia compared with respiratory epithelia. Thus, differential splicing efficiency between the various tissues which express CFTR provides one possible explanation for the reproductive tract abnormalities observed in infertile men with CFTR gene alterations but without other clinical manifestations of CF.

Cervex brush versus vaginal-cervical-endocervical (VCE) triple smear techniques in cervical sampling.

Cervex brush sampling was compared with the conventional triple vaginal-cervical-endocervical (VCE) smear technique. Nine hundred and fifty-nine Cervex brush smears and 1064 VCE smears were studied. All smears with both methods were technically satisfactory for evaluation. Endocervical cells were found in 90.7% and metaplastic cells in 73.3% of Cervex brush samples and in 92.5% and 64.1% of VCE samples, respectively. There were significantly more metaplastic cells in smears from premenopausal women. Low grade squamous intraepithelial lesion (SIL) was found in three Cervex brush samples and in two VCE samples. High-grade SIL was found only in one Cervex brush sample. Benign cellular changes were found in 142 Cervex brush samples and in 144 VCE samples. Sampling with the Cervex brush is efficient, simple and fast and gives high quality cervical smears for cytological evaluation.