A computational study of functional endoscopic sinus surgery and maxillary sinus drug delivery.

BACKGROUND: Topical medication is increasingly used following functional endoscopic sinus surgery (FESS). Information on particle sizes that maximise maxillary sinus (MS) delivery is conflicting, and the effect of antrostomy size on delivery is unclear. The purpose of this study was to estimate antrostomy and particle size effects on topical MS drug delivery. METHODOLOGY: Sinonasal reconstructions were created from a pre- and a post-FESS CT scan in each of four chronic rhinosinusitis patients. Additional models were created from each post-FESS reconstruction representing four alternative antrostomy sizes. Airflow and particle deposition were simulated in each reconstruction using computational fluid dynamics for nebulised and sprayed delivery. RESULTS: MS ventilation and drug delivery increased following FESS, the largest virtual antrostomy led to greatest delivery, and MS delivery was sensitive to particle size. Particles within a 5-18 µm and 5-20 µm size range led to peak MS deposition for nebulised and sprayed particles, respectively. Post-FESS increases in drug delivery varied across individuals and within individuals by the type of antrostomy created. CONCLUSION: Our findings suggest that FESS, particularly with larger antrostomies, improves topical drug delivery, and that certain particle sizes improve this delivery. Further research is needed to contextualise these findings with other post-surgical effects.

Treatment-seeking women at menopause: a comparison between two university menopause clinics.

OBJECTIVE: We wished to determine the expectations of women about the benefits of hormone replacement therapy (HRT) and how these expectations may be influenced by cultural factors and previous experience of disease by the patient or in their families. DESIGN: The attitudes of patients seeking HRT in Belfast, United Kingdom (n = 218) and Portland, USA (n = 100) were compared at their first clinic attendance using a questionnaire. Physical and mental health issues, previous use of HRT and continuance on treatment were compared. RESULTS: Belfast women were less healthy than their Portland counterparts, with a higher prevalence of cardiovascular disease and psychiatric disorders (p < 0.05). Belfast patients showed a significantly lower continuance with treatment (p < 0.01). Collectively, the patients ranked relief of menopausal symptoms as their main expectation from HRT followed by osteoporosis protection, psychiatric relief and cardioprotection. The Belfast group had higher expectations for the relief of psychological/psychiatric problems (p < 0.01). All women with a family history of cardiac disease or fractures were more concerned for the protective effects of HRT than those women with no relevant family history (p < 0.05). There were cultural difference in expectations from HRT with Belfast women expecting more psychological/psychiatric relief and therefore trying a greater number of preparations. CONCLUSIONS: These findings suggest that menopausal women in both countries are well informed about the potential protective benefits of HRT, and now expect an improvement in the quality of their lives well beyond the relief of menopausal symptoms.

A practical guide to prescribing hormone replacement therapy.

Over the past 20 years there has been increasing interest in the menopause and hormone replacement therapy (HRT). More recently, postmenopausal HRT has been seen as a specific treatment for symptoms in the short term and preventative therapy in the long term. Women must be counselled regarding the risks and benefits of HRT according to the best available evidence. The patient should also be actively involved in the decision regarding HRT therapy, which should then improve patient compliance. Generally, an appropriate regimen of HRT can be formulated for the majority of patients. Progestogen should be added to therapy in women with an intact uterus in a cyclical or continuous regimen. The management of common estrogenic and progestogenic adverse effects is important in improving compliance. At present, new drugs are being developed for the management of the menopause (selective estrogen receptor modulators and phytoestrogens). Obviously, further research will be necessary to determine whether these drugs have advantages over regular HRT. By offering postmenopausal women HRT an attempt is made to optimise their physical and psychological well-being. However, HRT is not without adverse effects, the most worrying of which is the possible increase in breast cancer risk with long term use. However, with patient education efforts, treatment regimens acceptable to both patient and practitioner can be initiated; in this regard, the aim of the practitioner should be to help the menopausal woman make the decision which is the most appropriate for her.

Differential effects of subcutaneous estrogen and progesterone on low-density lipoprotein size and susceptibility to oxidation in postmenopausal rhesus monkeys.

OBJECTIVE: To study the differential effects of subcutaneous E2 alone or in combination with P on the susceptibility of low-density lipoprotein (LDL) cholesterol to oxidation in naturally postmenopausal diet-controlled rhesus monkeys. DESIGN: Prospective, longitudinal controlled study. SETTING: Oregon Health Sciences University, Portland, Oregon, and Oregon Regional Primate Research Center, Beaverton, Oregon. PATIENT(S): Five naturally postmenopausal rhesus monkeys. INTERVENTION(S): Estradiol was administered subcutaneously for the first 4 weeks, followed by E2 plus P for 4 weeks, followed by a third 4-week washout period. MAIN OUTCOME MEASURE(S): Changes in plasma lipoprotein levels and oxidation of LDL and serum concentrations of E2 and P. RESULT(S): Levels of LDL cholesterol fell after 4 weeks of treatment with E2, compared with baseline. The lag time to half maximal light absorbancy after 4 weeks of E2 treatment was significantly increased compared with baseline. The maximal absorbance values and the slope of the propagation phase after 4 weeks of treatment with E2 were decreased compared with baseline. After 4 weeks of combined E2 and P treatment, all values were comparable to baseline. CONCLUSION(S): These results suggest that subcutaneous E2 therapy appears to enhance LDL resistance to oxidation and that this effect is attenuated by the addition of the P.

An intrauterine insemination-ready cryopreservation method compared with sperm recovery after conventional freezing and post-thaw processing.

OBJECTIVE: To test a sucrose-glycerol cryoprotectant for IUI-ready sperm preparation. DESIGN: Semen aliquots from normozoospermic donors either were subjected to conventional semen freezing (TES and Tris yolk buffer in 7.4% final glycerol) with post-thaw processing or were preprocessed and frozen in HEPES-buffered human tubal fluid with 1% human serum albumin, 4% sucrose, and 6% glycerol. All aliquots were cooled to 4 degrees C, exposed to liquid nitrogen vapors, and stored in liquid nitrogen. Aliquots from each were processed by centrifugation resuspension or by centrifugation in Percoll (Pharmacia, Alameda, CA) before sperm parameters were analyzed. SETTING: University-based andrology laboratory. MAIN OUTCOME MEASURE(S): Recovery of motile sperm. RESULT(S): Percoll processing produced preparations with higher percentages of motile cells; however, cryopreserved sperm had a lower recovery of motile sperm compared with Percoll-processed fresh semen or centrifugation/resuspension-processed fresh or frozen samples. The percentages of sperm with normal morphologies were significantly increased in the IUI-ready samples compared with samples frozen conventionally. The IUI-ready Percoll-processed sample produced the best results, with a final mean motility of 36% and an overall yield of motile sperm of 17.4%. CONCLUSION(S): The sucrose-glycerol-based cryoprotectant produced an IUI-ready preparation with motile sperm recovery comparable to that of conventional semen cryopreservation but with improved percent morphology.

Reactive oxygen species generation in human sperm: luminol and lucigenin chemiluminescence probes.

The objective of this study was to compare measurements of reactive oxygen species (ROS) generation from human spermatozoa in vitro using the luminol and lucigenin chemiluminescent probes. Luminol reacts with a variety of reactive oxygen species (H2O2, O2-, OH) and allows both intra- and extracellular ROS to be measured. Lucigenin, however, yields a chemiluminescence that is more specific for superoxide anions released extracellularly. Therefore, measurements made with both probes on the same samples should allow the intra- and extracellular components of ROS generation to be identified. Sperm samples from 47 men were divided into two equal aliquots, then processed by centrifugation and swim-up. Following further division into aliquots and the addition of the two chemiluminescent probes, Phorbol 12-myristate 13-acetate was added to trigger ROS release. Forty three percent of the sperm samples generated detectable levels of ROS. In the centrifuged preparations luminol produced a significantly higher peak luminescence than lucigenin. However, the sperm prepared by swim-up showed no significant differences in peak luminescence between luminol and lucigenin. The higher level of ROS generation produced by centrifugation may be due to membrane disruption or possibly the use of unfractionated cell suspensions. Extracellular ROS generation is more clinically important because surrounding healthy spermatozoa may be damaged. Therefore the lucigenin probe may be a more useful diagnostic tool than luminol for identifying sperm at risk of peroxidative damage after swim up preparation. The patients identified in this way may benefit from the addition of ROS scavengers to the culture medium in order to protect healthy sperm from collateral damage.

The effects of pentoxifylline on the generation of reactive oxygen species and lipid peroxidation in human spermatozoa.

The aims of this study were to compare the in vitro effects of 3.6 mM and 7.2 mM pentoxifylline on the ability of spermatozoa to generate reactive oxygen species (ROS) and on lipid peroxidation (LPO). Semen samples were obtained from 10 asthenozoospermic men who had been previously identified as producing ROS after addition of Phorbol 12-myristate 13-acetate (PMA) during the screening of patients attending with male factor infertility. Spermatozoa were prepared by a swim-up technique from unprocessed semen and divided into 3 aliquots. To the control aliquot [A] an equal volume of BWW medium was added. To aliquots B and C an equal volume of BWW medium containing pentoxifylline was added to obtain final concentrations of 3.6 and 7.2 mM, respectively. ROS production was measured from peak luminescence (mV 10(-7) sperm) using a lucigenin chemiluminescent probe. LPO was also measured in the medium surrounding the spermatozoa after 30 min exposure to pentoxifylline using the thiobarbituric acid (TBA) assay for malondialdehyde (MDA). The reduction in ROS production was significantly greater in the samples exposed to 7.2 mM pentoxifylline as compared with the control and 3.6 mM pentoxifylline samples. There was no significant difference in peak luminescence between control and 3.6 mM pentoxifylline specimens. Both concentrations of pentoxifylline caused comparable reductions in MDA concentration in the medium (P < 0.05) surrounding the spermatozoa compared with control after 30 min exposure. Extracellular ROS generation may damage surrounding healthy spermatozoa. These findings suggest that higher concentrations of pentoxifylline are protective against ROS release in susceptible spermatozoa and may also reduce collateral LPO.

Effect of glyceryl trinitrate on sperm motility and lipid peroxidation in normozoospermic men.

The objective of this study was to assess the in-vitro effects of the nitric oxide substrate glyceryl trinitrate (GTN) on sperm motility and membrane lipid peroxidation. Nitric oxide (NO) can impair sperm motility, possibly by an alteration of cyclic nucleotide levels. NO may also be protective against lipid peroxidation. Semen samples from nine normospermic men were prepared by a swim-up technique. Each specimen was divided into four aliquots, one of which was the control sample. The other three had 10(-6), 10(-8) or 10(-10) M GTN added. Sperm motility was then analysed over 180 min using a Hamilton Thorn motility analyser. Lipid peroxidation was assessed by measuring media malondialdehyde (MDA) levels at 180 min. Compared with control, the following measurements were reduced (p < 0.05) over the first 60 min in the 10(-6) M GTN aliquots only: mean path velocity (reduced by 14-15%), curvilinear velocity (reduced by 12-21%), straight-line velocity (reduced by 18-19%) and percentage of hyperactivated spermatozoa (reduced by 38-43%). MDA levels and head movement parameters were comparable amongst all aliquots (p > 0.05). The depressant effects of GTN on sperm motility appeared to be transient and reversible. The effects observed may be due to NO generated by GTN, or to GTN itself. This suggests that NO may have a role in vivo as a physiological inhibitor of sperm motility. The addition of GTN did not appear either to cause sperm membrane damage or to protect the spermatozoa from lipid peroxidation.

Total antioxidant capacity of seminal plasma is different in fertile and infertile men.

OBJECTIVE: To determine if the total antioxidant capacity of seminal plasma is different in fertile and infertile men. DESIGN: An enhanced chemiluminescence assay applied to seminal plasma from groups of fertile and infertile men. SETTING: The Assisted Conception Unit, Royal Maternity Hospital, Belfast. SUBJECTS: Men of proven fertility whose partners had an ongoing pregnancy resulting from IVF and male partners of couples attending our subfertility clinic. RESULTS: Total antioxidant capacity was significantly higher in seminal plasma from fertile men than from that of infertile men with normozoospermic samples that exhibited reactive oxygen species or asthenozoospermic samples with or without reactive oxygen species activity. CONCLUSIONS: Seminal plasma from infertile men has lower antioxidant levels than that of fertile men, particularly of patients whose semen have poor sperm motility. The presence of reactive oxygen species activity in sperm of infertile groups also is associated with lower levels of chain-breaking antioxidants in seminal plasma.

Reproducibility of sperm motility measurements in asthenozoospermic and normozoospermic individuals using the Hamilton-Thorn motility analyzer.

Computer-assisted semen analysis provides a useful, quantitative method for analyzing sperm movement parameters. However, few experimental data have been published on the measurement characteristics of CASA. This study measured the reproducibility of measurements of sperm motility using a Hamilton-Thorn motility analyzer. Twenty normozoospermic and 20 asthenozoospermic patients provided semen samples. Ten samples from each group were analyzed as unprocessed semen; the remainder were analyzed after washing. An aliquot from each sample was analyzed by CASA 10 times over an 18-min period. The mean coefficient of variation for all sperm motility parameters was less than 10%, except for the percentage of motile cells in the asthenozoospermic unprocessed samples, which was 17.1%. The mean coefficient of variation for percentage motility was reduced to 9.6% in the washed asthenospermic group. Other motility parameters were unaltered by washing in the asthenospermic samples. There were no substantial differences between the washed and unwashed normospermic measurements. Normospermic samples showed better reproducibility in measurement than asthenozoospermic samples. Washing reduced the difference, probably because of the removal of debris in the asthenozoospermic samples. The results indicate that serial measurements of sperm motility in both unprocessed and washed semen samples can be reliably made using the Hamilton-Thorn motility analyzer, and that reproducibility can be improved in asthenospermic samples by washing.

Persistent effects of pentoxifylline on human sperm motility, after drug removal, in normozoospermic and asthenozoospermic individuals.

The aim of the study was to compare the in vitro effect of pentoxifylline on human sperm motility when added prior to sperm selection and the persistence of the response after drug removal in normo- and asthenozoospermic individuals. The sperm samples were obtained from 22 men who were repeatedly asthenozoospermic or normozoospermic. Sperm movement was measured using computer-assisted semen analysis over 180 min. Percentage motility and progressive motility were increased in both normo- and asthenozoospermic samples (P < 0.05). Curvilinear velocity, amplitude of lateral head displacement and beat-cross frequency were increased in both groups (P < 0.05). Straight-line velocity was increased significantly in the normozoospermic group only. In both normo- and asthenozoospermic individuals pentoxifylline appeared to enhance sperm motility for at least 180 min after drug removal. This should prevent any potentially toxic effects of the drug on oocytes if it is used to enhance sperm motility during in vitro fertilization.

Influence of pentoxifylline on human sperm motility in asthenozoospermic individuals using computer-assisted analysis.

This study was conducted to evaluate the in vitro effects of pentoxifylline on sperm motility from asthenozoospermic men. The sperm were prepared by a swim-up technique from the unprocessed semen. After centrifugation, sperm were resuspended in the presence or absence (controls) of 3.6 mM pentoxifylline in Earle's solution for up to 180 min. Sperm motility was measured using computer-assisted (Hamilton-Thorn Research) semen analysis. Pentoxifylline significantly increased the numbers of motile (+28-80%) and progressively motile (+54-117%) sperm over the 180 min studied. These changes were accompanied by increases in the progressive velocity (VSL, +11-44%) and curvilinear velocity (VCL, +12-22%) up to 120 min after exposure to the drug. Concomitant changes were observed in the amplitude of lateral head displacement (ALH, +5-17%) up to 60 min and the beat cross frequency (+16-34%) between 60 and 180 min. The results suggest that pentoxifylline consistently enhances both the numbers of motile and progressively motile sperm and the quality of their movement.

Familial fugue--a case report.

A case of fugue with a familial pattern is presented. A review of the pertinent literature has been made. A "learned" basis to the development of fugue in the case presented is considered.