Ipsilateral testicular catch-up growth rate following microsurgical inguinal adolescent varicocelectomy. The role of testicular volume in adolescents with varicocele: the better way and time of surgical treatment. Lymphatic sparing microscopic retroperitoneal varicocelectomy: a preliminary experience. Optimizing the outcome of microsurgical subinguinal varicocelectomy using isosulfan blue: a prospective randomized trial. Microsurgical spermatico-epigastric venous anastomosis in the treatment of varicocele in children: assessment of long-term patency. Varicocelectomy in adolescent boys: long-term experience with the Palomo procedure. Recurrence of varicocele after high retroperitoneal repair: implications of intraoperative venography. Angiographic findings of primary versus salvage varicoceles treated with selective gonadal vein embolization: an explanation for surgical treatment failure. Varicocele retrograde embolization with boiling contrast medium and gelatin sponges in adolescent subjects: a clinically effective therapeutic alternative. Pediatric Varicocele, Micropenis, Buried and Webbed Penis, Penile Torsion, Diphallia, Penoscrotal Transposition, and Aphallia 209 72. Retrograde percutaneous sclerotherapy of left idiopathic varicocele in children: results and follow-up. Percutaneous sclerotherapy of idiopathic varicocele in childhood: a preliminary report. Treatment by sclerotherapy and percutaneous embolization: reflections on the method. Initial experience with 3% sodium tetradecyl sulfate foam and fibered coils for management of adolescent varicocele. Initial experience with percutaneous selective embolization: A truly minimally invasive treatment of the adolescent varicocele with no risk of hydrocele development. Results and complications of adolescent varicocele repair with intraoperative sodium morrhuate sclerotherapy. Sclerotherapy of the pampiniform plexus with modified Marmar technique in children and adolescents. Laparoscopic surgery for adolescent varicocele: preliminary report on 80 patients. Reactive hydrocele after laparoscopic Palomo varicocele ligation in pediatrics [Article in English, Spanish]. Laparoscopic Palomo varicocelectomy in the adolescent is safe after previous ipsilateral inguinal surgery. Laparoscopic varicocelectomy with preservation of the testicular artery in adolescents. Laparoscopic treatment of pediatric varicocele: a multicenter study of the italian society of video surgery in infancy. Varicocele and adolescents: semen quality after 2 different laparoscopic procedures. Laparoscopic surgery of deferential reflux in pediatric and adolescent varicocele. Evaluation of 100 laparoscopic varicocele operations with preservation of testicular artery and ligation of collateral vein in children and adolescents. Laparoscopic Palomo varicocele ligation in children and adolescents: results of 103 cases. LigaSure vessel sealing system in laparoscopic Palomo varicocele ligation in children and adolescents. Laparoscopic varicocelectomy in adolescents using an ultrasonically activated scalpel. Lymphatic sparing versus lymphatic non-sparing laparoscopic varicocelectomy in children and adolescents: a systematic review and meta-analysis. Lymphography prior to laparoscopic Palomo varicocelectomy to prevent postoperative hydrocele. Pediatric Varicocele, Micropenis, Buried and Webbed Penis, Penile Torsion, Diphallia, Penoscrotal Transposition, and Aphallia 211 118.
In the lower fourth of the abdomen, the posterior aponeurotic layer of the sheath terminates in a free crescentic margin, the semilunar fold of Douglas. Each rectus abdominis muscle, encased in the rectus sheath on either side of the midline, extends from the superior aspect of the symphysis pubis to the anterior surface of the fifth, sixth, and seventh costal cartilages. A variable number of tendinous intersections (three to five) crosses each muscle at irregular intervals, and any transverse rectus surgical incision forms a new fibrous intersection during healing. The muscle is not attached to the posterior sheath and, following separation from the anterior sheath,canberetractedlaterally,asinthePfannenstiel incision. Each rectus muscle has a firm aponeurosis at its attachment to the symphysis pubis, and this tendinous aponeurosis can be transected if necessary to improve exposure, as in the Cherney incision, andresuturedsecurelyduringclosureoftheabdominalwall. They enter the rectus sheaths at the level of the semilunar line and continue their course superiorly just posterior to the rectus muscles. Although it does not always give sufficientexposureforextensiveoperations,ithascosmetic advantages in that it is generally only 2cm above the symphysis pubis, and the scar is later covered by the pubichair. Whenitisanticipatedthatupperabdominalexploration will be necessary, such as in a patient with suspected ovarian cancer, a midline incision through the linea alba or a paramedian vertical incision is indicated. Othergrowthfactors and peptides such as inhibin-A, inhibin-B, and activin actsystemicallyandlocallytocontrolfolliculargrowth. After oocyte release, the dominant (graafian) follicle becomesthecorpusluteumandsecretesbothestradiol (E2)andprogesterone(P4). Theendometriumresponds toE2withgrowthorproliferationbeforeovulationand toP4andE2afterovulationwithmaturationthatallows for implantation if fertilization occurs. Fertilizationandimplantationbeginwithnormalsperm function and penetration of the oocyte in the fallopian tube. Fertilization restores the diploid number of chromosomesanddeterminesthesexofthezygote. Thefertilizedovumreachestheendometriumabout3daysafter ovulation and after another several days the blastocyst implants. The villiarefirstdistinguishedaboutthe12thdayafterfertilization and are the essential structures of the placenta. Reproductive Cycle Each female reproductive cycle (menstrual cycle) represents a complex interaction between the hypothalamus, pituitary gland, ovaries, and endometrium. Similarchangesattheleveloftheendometriumallow forsuccessfulimplantationofthefertilizedovumora physiologic shedding of the menstrual endometrium when an early pregnancy does not occur. By convention,thenormalcyclebeginsonthefirstdayofmenstrual bleeding and ends just before the first day of the next menses. The reproductive cycle can be viewed from the perspective of each of four physiologic com ponents (Table 4-1). The cyclic changes within the hypothalamic-pituitary axis, ovary, and endometrium aresequentiallyapproachedinthischapter,asifthey werefourseparatecycles,buttheseendocrineevents occurinconcertinauniquelyintegratedfashion. Pulses are more frequent and lower amplitude in follicular phase and less frequent but higher amplitude in luteal phase (see Figure 4-4). Because it is visible, it is where the cycle is said to start but menstruation actually represents the end of the previous cycle. Estradiol (E2) from the ovary stimulates growth (proliferation) and progesterone (P4) from the corpus luteum converts endometrium to secretory and withdrawal of E2 and P4 leads to menstruation (see Figures 4-7 and 4-8). Thepituitaryglandisdividedintotwo major portions, the neurohypophysis and the adenohypophysis(Figure4-1). The neurohypophysis, which consists of the posterior lobe (pars nervosa), the neural stalk (infundibulum), and the median emi nence, is derived from neural tissue and is in direct continuity with the hypothalamus and central nervous system. The adenohypophysis, which con sists of the pars distalis (anterior lobe), pars inter media (intermediate lobe), and pars tuberalis, which surrounds the neural stalk, is derived from ectoderm. The arterial blood supply to the median eminence and the neural stalk (pituitary portal system) represents a major avenue of transport for hypothalamic secretionstotheanteriorpituitary. Theneurohypophysisservesprimarilytotransport oxytocinandvasopressin(antidiuretichormone)along neuronal projections from the supraoptic and paraventricularnucleiofthehypothalamustotheirrelease intothecirculation. The difference in half-lives may account, at least in part, for the differential secretion patterns of these two gonadotropins. Mamillary body Median eminence Pars tuberalis Hypophyseal portal veins Optic chiasm Hypophyseal artery Pars nervosa of the neurohypophysis Adenohypophysis Prolactinissecretedbylactotrophs.
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An evaluation of a zero-heat-flux cutaneous thermometer in cardiac surgical patients. Comparison of temporal artery thermometer to standard temperature measurements in pediatric intensive care unit patients. Grant acknowledgement None A805 Viral bronchiolitis in pediatric acute respiratory distress syndrome N. Patients with a diagnosis of congenital heart disease or pre-existing chronic lung disease were excluded. Test of bivariate association were performed using Mann Whitney U test and chi square test. A804 An evaluation and accuracy of new zero-heat-flux thermometer (3 M SpotOn) in pediatric intensive care patients M. Goto2 1 Yokohama City University Hospital, Intensive Care Unit, Yokohama, Japan; 2Yokohama City University Hospital, Department of Anesthesiology, Yokohama, Japan Correspondence: M. Although the usefulness and accuracy of SpotOn system in adult patients have been demonstrated, there are no reports on pediatric intensive care patients. Objectives: the aim of this study was to evaluate the effectiveness of a new temperature measurement system attached to the forehead, and compare it to rectal temperature sensors in terms of correlation and accuracy. Core temperature was measured and recorded at every minute from the both thermistor of a rectal thermal probe and with SpotOn in these patients. The data when the forehead sensor or rectal probe was taken out for nursing care was excluded from statistical analysis. In all patients, SpotOn showed higher than Intensive Care Medicine Experimental 2016, 4(Suppl 1):28 Page 411 of 607 References 1) Pediatric Acute Lung Injury Consensus Conference Group, et al. Pediatric acute respiratory distress syndrome:consensus recommendations from the Pediatric Acute Lung Injury Consensus Conference. After approval by research ethics committee,informed consents were obtained from parents and pediatric cases aged from 1 month-18 years and stayed for > 48 h were enrolled. Alterations in platelet count and mean platelet volume as predictors of patient outcome in the respiratory intensive care unit. There is growing urgency to develop a core set of outcome measures which can be adopted in clinical and research practice to evaluate efficacy in response to interventions such as rehabilitation. Methods: Multi-centre prospective observational study conducted across four sites internationally. Results: 128 participants have been recruited into the study to date across the four sites. Aim 2: Preliminary exploration of a subgroup with complete data at hospital discharge (n = 73) was evaluated. A new transformed scale based on rasch analytical principles is promising combining features of both tools for evaluation of functional recovery of critically ill. Methods: We performed a retrospective cohort study in one Boston teaching hospital on 2,828 adults who received critical care from 1997 to 2011 and survived hospitalization. The exposure of interest was functional status determined by a licensed physical therapist based on the functional mobility sub scales of the Functional Independence Measure. Increased intensity of physical therapy is associated with improved mortality outcomes. A809 Does enhanced physiotherapy and early mobilisation reduce the degree of muscle loss for patients admitted to critical care
Encouragement for coverage for Tai Chi could be addressed by simply adding it to the list of services that should be covered "if available. Staff feels that a patient with centralized pain syndrome would likely not receive functional benefit from opioids, and in that case would fail to meet the opioid prescribing criteria in the guideline. Additional requests from stakeholders include: 1) Information on the number of patients who would be affected by the proposed changes to the Prioritized List. Staff is working on obtaining these numbers and will present them in the formal Powerpoint presentation at the meeting. The Pharmacy and Therapeutics Committee staff have prepared a formal evidence review on this topic which is included in the packet. Expert input brought additional literature to P&T staff attention and is included in this review if it met inclusion criteria. A higher threshold is appropriate in a case like this due to the known harms associated with opioid therapy in order to ensure benefits outweigh harms at a similar level compared to treatments without significant harms. Proposed ranking would put this line in the funded region, around line 443 (near the funding line, which is currently below line 469). Modifies the paragraph on tapering for chronic opioid use to match wording in new chronic pain conditions guideline b. Once the pre-determined goals of care have been achieved, an additional two visits may be authorized for maintenance therapy to maintain these improvements. Less frequent monitoring may be appropriate for certain medications after safety and efficacy are established. Opioid tapering should be done on an individualized basis which includes a taper goal of zero. During the taper, behavioral health conditions need to be regularly assessed and appropriately managed. Patients lacking red flag symptoms should be assessed using a validated assessment tool. These therapies are only included on these lines if provided by a provider licensed to provide the therapy and when there is documentation of measurable clinically significant progress toward the therapy plan of care goals and objectives using evidence based objective tools. Rehabilitation services provided under this guideline also count towards visit totals in Guideline Note 6. Transitional coverage for patients on long-term opioid therapy as of July 1, 2016: For patients on covered chronic receiving long-term opioid therapy (>90 days) for conditions of the back and spine as of July 1, 2016, opioid medication is included on these lines only from July 1, 2016 to December 31, 2016. During the period from January 1, 2017 to December 31, 2017, continued coverage of opioid medications requires an individual treatment plan which includes a taper plan developed by January 1, 2017 which includes a taper with an end to opioid therapy no later than January 1, 2018. Opioid tapering should be done on an individualized basis and include a taper goal to zero. Treatments may be billed to a maximum of 30 minutes face-to-face time and limited to 12 total sessions per year, with documentation of meaningful improvement; patients may have additional visits authorized beyond these limits if medically appropriate. The review focuses specifically on treatment of fibromyalgia as non-analgesics for treatment of chronic non-cancer pain or neuropathic pain have been reviewed previously. What is the efficacy and safety of pharmacotherapy for treatment of fibromyalgia compared to placebo, other pharmacological therapies, or nonpharmacological treatments Are there any subgroups (based on age, gender, ethnicity, comorbidities, disease duration or severity) for which pharmacotherapy for fibromyalgia is more effective or associated with more long-term adverse effects Conclusions: There is no moderate or high strength evidence for any pharmacological treatment compared to placebo or other therapy. Like many other conditions for chronic pain, evidence supporting benefit of long-term pharmacological treatment for fibromyalgia is limited, efficacy of pharmacotherapy is relatively modest, and clinical trials often document a large placebo response upon evaluation of symptom improvement. Pharmacological interventions with the most evidence of benefit include duloxetine, milnacipran, and pregabalin, but applicability to a broader population is limited. In many trials, patients with comorbid medical conditions, particularly mental health conditions, were excluded. Similarly, many patients with a placebo response during run-in periods were excluded from trials. The strongest available evidence for efficacy outcomes for fibromyalgia drugs was of low strength meaning there is limited confidence that the estimated effects in the studies reflect the true effect, and further research is likely to change the estimated effect. There is insufficient evidence on long-term use of pharmacological therapy for treatment of fibromyalgia, and it is unclear if modest improvements in pain outcomes would be sustained over time.
Finally, the placenta should be examined to ensure its complete removal (no missing cotyledons) and to detect placental abnormalities. A, Gentle downward traction on the head is applied to deliver the anterior shoulder. Ifanepisiotomyhasbeenperformed(Figure8-13), it should be repaired as illustrated in Figure 8-14. Absorbable sutures (size 00) should be used, and a rectal examination should be done to ensure that the sutures have not inadvertently transected the rectal mucosa. Fourth Stage of Labor the hour immediately following delivery and the first 4 hours postpartum require continued close observa- tion of the patienttopreventpostpartumhemorrhage. Bloodpressure,pulserate,anduterinebloodlossmust bemonitoredclosely,anditisimportanttoinstructthe patient on massaging the uterus to maintain uterine tone. It is during this time that serious postpartum hemorrhagemostcommonlyoccurs,butsomewomen mayhavefrequentbleedingforupto10dayspostpartum, usually because of uterine relaxation, retained placental fragments, or unrepaired lacerations. An increase in pulse rate, often out of proportion to any decreaseinbloodpressure,mayindicatehypovolemia. Puerperium the puerperium consists of the period following delivery of the baby and placenta to approximately 6 weeks postpartum. Duringthepuerperium,thereproductiveorgansandmaternalphysiologyreturntothe prepregnancy state, although menses may not return formuchlonger. Vagina Although the vagina may never return to its prepregnancy state, the supportive tissues of the pelvic floor graduallyregaintheirformertone. Womenwhodeliver vaginallyshouldbetaughtandencouragedtoperform Kegelexercises(intermittenttighteningoftheperineal muscles) to maintain and improve the supportive tissuesofthepelvicfloor. For the first few days after delivery, the uterine discharge (lochia) appears red (lochia rubra), because of the presence of erythrocytes. After3to4days,thelochiabecomespaler(lochia serosa), and by the tenth day, it assumes a white or Cardiovascular System Immediately following delivery, there is a marked increase in peripheral vascular resistance because of theremovalofthelow-pressureuteroplacentalcirculatory shunt. The cardiac output and plasma volume graduallyreturntonormalduringthefirst2weeksof thepuerperium. A taped sponge is placed in the upper vagina, and a continuous, locked 00 or 000 absorbable suture is used to close the vaginal epithelium from the apex to the hymeneal ring. B, Three interrupted sutures are used to close the deep perineal fascia (of Colles) and underlying levator ani muscles. The vaginal epithelial suture is brought below the skin into the subcutaneous tissue. C, the same continuous suture is used to close the superficial fascia down to the anal edge of the episiotomy. D, the same suture is used as a subcuticular stitch brought back to the hymeneal ring, where it is doubly tied. Psychosocial Changes It is fairly common for women to exhibit a mild degreeofdepressionafewdaysfollowingdelivery. Recently, a relationship between vitamin D deficiency (<20 ng/mL) or insufficiency (20 to 29 ng/mL) and depression has been reported. Ifapatienthassymptomsofdepression,she should be screened using the Edinburgh Postnatal Depression Scale. Any prolonged episodes of depression during or after pregnancy should receive urgent attention. The process is then completed in the same way as with a midline episiotomy repair. Return of Menstruation and Ovulation In women who do not nurse, menstrual flow usually returnsby6to8weeks,althoughthisishighlyvariable. Althoughovulationmaynotoccurforseveralmonths, particularly in nursing mothers, contraceptive use shouldbeemphasizedduringthepuerperiumtoavoid anundesiredpregnancy. First, breast milk is the ideal food for the newborn, is inexpensive, and is usually in good supply. Second, nursing accelerates the involution of the uterus because suckling stimulates the release of oxytocin, therebycausingincreaseduterinecontractions. Third, andprobablymostimportant,there are immunologic advantages for the baby from breastfeeding. Breastfeeding thereby provides the newborn with passive immunityagainstcertaininfectiousdiseasesuntilitsownimmunemechanismsbecomefully functional by 3 to 4 months.
Syndromes
Treatment with open or percutaneous bilateral pedicle screws, resulted in maintenance of Cobb correction at 12 months (p>0. Whole-spine radiographs were taken with the patients in standing preoperatively and 3-month, 12-month and 24-month postoperatively. Changes of each dependent variable were compared at consecutive timepoints in each group. Approximately 17% of patients had lower extremity numbness, pain, or described other sensation changes after surgery that were not present pre-operatively. This is thought to be related to the approach required to access the anterior column through the psoas. However, the approach does avoid the potential for vascular injury encountered with traditional anterior spinal fusion and may reduce the risk of dural tears or direct injury to the posterior neural elements that can occur with posterior interbody fusion approaches. Potential advantages to this approach include avoidance of the great vessels and peritoneal viscera. An outcome assessment questionnaire was mailed to patients who had not recently been evaluated in the clinic. The initial evaluation of a patient with thoracolumbar spine trauma is often performed by the most inexperienced orthopedic surgeon, typically an Intern or junior level Resident, and relaying meaningful information to a Staff spine surgeon is imperative for safe efficient care and initial treatment decision making. Each participant evaluated the same cases on three different occasions within a four week time period. However, the intra-observer reliability was not acceptable for Intern and junior level Resident evaluators with respect to evaluation of fracture morphology (r = 0. In regard to inter-observer reliability, there was acceptable agreement for all evaluators in regards to treatment recommendation and total score, however there was not acceptable agreement for evaluation of fracture morphology (r = 0. The sequestered disc classified by the extent of migration(to proximal 1/3, middle 1/3, distal 1/3 of vertebral body height, Fig 3,4). Interestingly, back pain redeveloped around 2 year follow-up and then subsided afterward(Fig 7). Surgical treatment includes posterior wiring/plate fixation, anterior cervical discectomy with plating, as well as combined anterior and posterior instrumentation. The present study was aimed at comparing a novel anterior fixation technique to a combined anterior and posterior instrumentation technique. However, they are associated with complications such as pseudoarthrosis, graft or plate dislodgment and loss of lordotic alignment. The major advantage of this anterior approach may be that the decompression, reduction, interbody grafting, and instrumental stabilization can all be performed using the same operative incision. In lateral bending and axial rotation, there were higher percentage changes between constructs. While a 3-fold decrease in the amount of protein in the simulator fluid increased the wear by approximately 10% (Gr 3 vs. All implants for each group maintained full functionality throughout each test duration. Visual and light microscopy revealed no evidence of gross deformation, delamination or fatigue cracks in the implants after testing. Closer examination under light microscopy revealed an abrasive wear mechanism occurring, with scratches and highly polished surfaces for all groups. There were no notable differences in the images suggesting that third body wear was occurring (Gr 5). Significant differences between wear rates were determined via the Wald test (p< 0.
Knowing that wood with differing densities tends to move different distances before being deposited in a stable position, lower density trees like Balsam fir might be the species of choice if the target restoration area is far from the insertion point whereas higher density wood such as White birch might be a better choice if the target area is close by. Furthermore, given that wood placed at lower elevation in the channel likely moves before wood staged closer to the bank-full elevation, higher density wood could be placed lower in the channel and lower density wood closer to the bank-full stage if the desire is to form log jams close to the insertion point. Wood insertion points can be prioritized based on the knowledge that wood tends to accumulate in areas of rapid geomorphic change such as at valley constrictions, slope breaks, and changes in channel planform. While adding wood anywhere on streams where wood has been removed by past human activities is likely to be beneficial, careful study of geomorphic conditions and the patterns of wood movement and accumulation will lead to even greater benefits with less effort and a lower likelihood of unintended damage to adjacent infrastructure. We suggest that wood used for restoration need not always be anchored, that its movements are largely predictable and stable after the initial transport, and that mobile wood additions are a cost effective tool to create habitat and channel complexity. Our results are consistent with a passive approach to in-stream wood restoration in which it is the process of wood recruitment that is restored (Kali et al. Interaction of large woody debris, channel hydraulics and habitat formation in large rivers. Patterns and processes of wood debris accumulation in the Queets river basin, Washington. Characteristics and function of large woody debris in streams draining old-growth, clear-cut, and second-growth forests in southwestern Washington. Colonisation of introduced timber by algae and invertebrates, and its potential role in aquatic ecosystem restoration. The use of large wood in stream restoration: experiences from 50 projects in Germany and Austria. AcknoWlEdgmEntS the authors wish to acknowledge all of the organizations and individuals that provided project funding, including the Eastern Brook Trout Joint Venture, New Hampshire Charitable Foundation, New Hampshire Department of Environmental Services, and New Hampshire Fish and Game Department. Fish passage facilities and anadromous fish restoration in the Connecticut River basin. At the first symposium, two fisheries biologists attacked wild trout management as a standalone management technique, arguing that ending catchable-sized trout stocking entirely was an idea of "some elitist trout fishermen and a few fishery biologists" (Wiley and Mullan 1975). While the authors correctly pointed out that wild trout management was not suitable for all fisheries, they overlooked a much longer and expansive history of wild trout ethics and management that went beyond a handful of elitist anglers and biologists. I address this history with more depth in my forthcoming book from the University of Washington Press, but here I will attempt to outline some of the broad changes in American conceptions of nature and the wild as well as the changing ideals and techniques of anglers and fisheries managers in the twentieth century. Indeed, the northern European roots of the word wilderness translate to the "place of wild beasts" (Nash 1982). In the Middle Ages, Europeans saw forests as scary, dark places and peasants rarely ventured far from their small villages (Manchester 1993). The original fairy tales emerged not as fun, Disneyfied stories, but as violent and bawdy tales over food, family size, and the ever-present threats of nature. As they colonized the Americas, Europeans brought these traditions with them; one pilgrim leader, William Bradford, later wrote that the land that lay before them was "but a hideous and desolate wilderness, full of wild beasts and wild men" (Quoted in Nash 1982). Within the Euro-american cultural tradition, then, the idea of wild was not celebrated. Nature and its creatures remained a place to be transformed into civilization-or avoided entirely. This concept of nature changed when the rise of industrial capitalism and nation-states ushered the world into the modern era. In response to this new industrialized, modern world in the nineteenth century, many Americans began to see the wild qualities of nature in a more positive light. Influenced by Romanticism, evangelical revivalism in the wake of the Second Great Awakening, and nationalism, many Americans connected nature to God, redefining the sublime to appreciate the awe of wild landscapes (Novak 1980). The growing leagues of leisure class anglers also held sentimental views of nature. One sporting writer liked that fly fishing took place "amongst the most picturesque panorama designed by nature" (Fitzgibbon 1853). Within this shift, the growing middle class both benefitted from the exploitation of nature and used it as a place for play; they increasingly headed outdoors to spend their leisure time and money on recreational activities (Merchant 1989, see also Schmitt 1969).
Offer genetic counseling and infertility evaluation when questions about these topics arise. Educate men about the risk of heritability of Spina Bifida for their offspring and offer their female partners additional supplementation with folic acid to reduce the risk. There is a need to characterize sexual function and interest among men with Spina Bifida. There is a lack of understanding about the impact of sexual dysfunction on quality of life among men with Spina Bifida. There is a need to characterize the incidence and etiology of hypogonadism in men with Spina Bifida. Mechanisms should be developed and standardized to assess and monitor penile/genital sensation in men with Spina Bifida. The prevalence and nature of penile/genital sensation based on the type and level of lesion in men with Spina Bifida needs to be characterized. There is a need to understand the prevalence and nature of erectile dysfunction in men with Spina Bifida. Validated questionnaires for erectile, ejaculatory, and orgasmic dysfunction specific to men with Spina Bifida or other congenital neuropathies are needed. The extent of the effect of sexual dysfunction (erectile, ejaculatory, and orgasmic), decreased genital sensation, and fertility concerns on quality of life in adult men with Spina Bifida remains uncharacterized. There is a lack of information on the prevalence of infertility, and mechanisms to treat infertility in men with Spina Bifida are undefined. The impact of infertility and paternity on the overall quality of life in men with Spina Bifida is unknown. Information is needed on the use, safety, and need of latex-free condoms in men with Spina Bifida. Research is needed to determine whether early sensation is predictive of future male sexual function. Information is needed to determine the best strategies to promote anatomical awareness and a healthy self-identity, and to avoid sexual abuse. There is a need to improve the characterization of paternity goals and outcomes in men with Spina Bifida. Adequately assess pre-treatment bowel, urinary, and sexual function to guide counseling about treatment options for prostate cancer. Prior to decision-making for treatment of prostate cancer, men with Spina Bifida may benefit from adjunct testing to fully characterize the risks of various treatments. No studies have been conducted to investigate outcomes after treatment for prostate cancer in men with Spina Bifida. Determine the effect of intermittent self-catheterization on prostate-specific antigen testing. Define the role of digital rectal exams on cancer screening in men with Spina Bifida. What young people with spina bifida want to know about sex and are not being told. Cryptorchidism in spina bifida and spinal cord transection: a clue to the mechanism of transinguinal descent of the testis. Evaluation and Treatment of Cryptorchidism- American Urological Association Guidelines. Sexuality in relation to independence in daily functions among young people with spina bifida living in Israel. The effect of spinal cord level on sexual function in the spina bifida population. Can clinically significant prostate cancer be detected with multiparametric Magnetic resonance imaging Prostate cancer screening with prostate specific antigen in spinal cord injured men. Effect of inflammation and benign prostatic hyperplasia on elevated serum prostate antigen levels. Evolution of free, complexed, and total serum prostatespecific antigen and their ratios during 1 year follow up of men with febrile urinary tract infection. Sexual health requires a positive and respectful approach to sexuality and sexual relationships, as well as to the possibility of having pleasurable and safe sexual experiences, free of coercion, discrimination, and violence. It is important to provide people with Spina Bifida with opportunities to acquire relevant and accurate knowledge about sexual health, and to develop and implement skills to negotiate sexual desire, intimacy, and activity.
Mammalian gene promoters are often associated with CpG-rich regions (CpG islands), and their methylation state is highly dynamic during different stages of development (Antequera and Bird 1993). Experimental evidence indicates that the fidelity of maintenance methylation is in the range of 95 99% (Genereux et al. Many studies have attempted to elucidate the mechanism of methyl group addition to the cytosine residue (Hashimoto et al. In contrast, the mechanism(s) or the enzyme(s) performing the demethylation process is still unknown. Another group of epigenetic modifications occur at the octamer units of histone proteins. The protruding tails of histone proteins are the site for multiple posttranslational modifications, such as acetylation, methylation, and phosphorylation (Jenuwein and Allis 2001). Histone acetylation is invariably associated with high gene expression (Choi and Howe 2009; Wade et al. In contrast, different combinations of histone methylation and phosphorylation can correlate with either gene activation or repression, depending on the residue on which the mark is present (Bartova et al. The opposing activity of these enzymes provides a dynamic equilibrium between chromatin structure and associated gene transcription. This diversity of histone modifications provides multiple degrees of flexibility, as the sum of histone modifications at a particular promoter region defines a specific epigenetic state of a gene and guides it for activation or silencing. Thus, cell types within a tissue and different tissue types have distinct "epigenotypes" to suit their needs of differential gene expression and provide phenotypic plasticity for a fixed genotype (Cheung et al. Although it has been generally accepted that, during meiosis, the epigenetic marks are erased in the germ cells and new profiles restated, emerging evidence shows that select loci may escape this complete germline erasure of epigenetic marks, resulting in transgenerational phenotypic effects (Jaenisch and Bird 2003; Klar et al. In our view, the epigenetic model of complex disease has great biological and predictive utility. It presents us with the opportunity to investigate and elucidate the peculiar nature of complex diseases with a new theoretical framework and innovative experimental approaches. The pre-epimutation(s) does not result in a diseased condition, but rather predisposes an individual to developing the disease. The pre-epimutation can be influenced by numerous pre- and post-natal influences, such as tissue differentiation, external environment, hormones, stochastic events, etc. Such epigenetic differences in twins can result in full or partial discordance (variations arise in age of onset, disease severity, drug response). Molecular epigenetic differences have been identified in inbred animals (Rakyan et al. Skewing of X chromosome inactivation is found in many disorders, such as X-linked immunodeficiencies, Lesch Nyhan disease, and incontinentia pigmenti, among others (Schueler et al. It has been observed that approximately 50% of female carriers for X-linked mental retardation exhibit skewed X inactivation with an activation ratio of 80:20% or higher between the two X chromosomes (Plenge et al. Such differences have traditionally been linked with genetic risk factors on sex chromosomes. In addition, gender-specific effects have been attributed to sex hormones and their crucial role in various regulatory processes and disease states (Arnold 2003; Sit 2004). Interestingly, several genetic association studies revealed that autosomal genes also may exhibit sex effects (Kaminsky et al. Sex Understanding Bipolar Disorder: the Epigenetic Perspective 37 hormones are known to mediate changes in gene expression through epigenetic modifications of target genes. These modifications primarily affect the chromatin structure, making associated genes transcriptionally active or repressed. Moreover, the effect of sex hormones has been shown to be gene- and tissuespecific due to differential tissue-specific distribution of sex hormone receptors between the sexes and their target genes (Azzi et al. From these studies, it is plausible to assume that specific alleles or haplotypes implicated in linkage and association studies might become risk factors only after epigenetic alteration mediated by the endocrine system. Other modes of inheritance that might explain parent-of-origin effects are mitochondrial inheritance and genomic imprinting. Genomic imprinting refers to monoallelic expression of several hundred genes, mainly attributed to the differential epigenetic signatures at maternal or paternal alleles. Imprinted genes are present in clusters and may exhibit epigenetic regulation in a tissue-specific manner.
Thefetal adrenal and the placenta do not participate significantly in aldosterone production, although the fetal adrenal is capable of synthesizing it. Aldosterone stimulates the absorption of sodium and the secre- Parturition Parturitionmeanschildbirth,andlaboristhephysiologic process by which a fetus is expelled from the uterustotheoutsideworld. While skeletal muscle requires innervation, contraction of smooth muscles such as the myometrium is triggered primarily by hormonal stimuli. C H A P T E R 5 Endocrinology of Pregnancy and Parturition 59 Glycerol Arachidonic acid Fatty acid Phosphate Phosphate Inositol mation concerning the control of the human gestational length or the mechanisms that control the initiationoflabor. Animal Models Most studies have been conducted in sheep, where the fetus appears to control the onset of labor. The cortisol surge induces the placental enzyme 17-hydroxylase and the formation of androgens, which are precursors of estrogen (see Figure 5-1), while simultaneously decreasing progesterone formation. The rise in the estrogen-toprogesterone ratio leads to (1) greater secretion of prostaglandins;(2)formationofmyometrialgapjunctions,whichprovideareasoflowresistancetocurrent flowandincreasecoordinateduterinecontractions;(3) cervicalripening;and(4)theonsetoflabor. In a breed of Guernsey cows with a genetic defect resulting in fetal pituitary and adrenal dysfunction, pregnancy is prolonged, and normal vaginal delivery does not occur. In the rabbit, parturition directly follows a decline in progesterone production secondary to a decline in corpus luteum function. Thebindingofoxytocinandprostaglandinstotheir respectivereceptorsactivatesphospholipaseC,which hydrolyzes phosphatidylinositol bisphosphate, a lipid presentinthecellmembrane,toinositoltrisphosphate anddiacylglycerol(Figure5-4). Inositoltrisphosphate induces release of calcium from the sarcoplasmic reticulum, an intracellular calcium storage area. The maintenance of adequate maternal calcium levels is important because low maternal serum calcium levels have been observed in women at risk for cesarean delivery. Unlike the heart, in which the bundle of His is present, no anatomic structures for synchronization of contractions have been found in the uterus; however, recently it has been observed that vitamin D deficiency during pregnancy is associated with myometrial dysfunction and a greater risk of cesarean delivery. Estradiol and prostaglandins promote the appearance of gap junctions, whereas progesterone opposes this action of estradiol. The Human Based upon animal and human research, the process of normal spontaneous human parturition can be dividedintofourstages. Each species has not only a unique gestational length, but also unique mechanisms for controlling that length. Thus, although animal models provide importantinsights,theydonotprovidespecificinfor- nancy, the uterus remains relatively quiescent. Myometrial activity is inhibited during pregnancy by varioussubstances,butprogesterone appears to play a central role in maintaining uterine quiescence. Rare uterine contractions that occurduringthequiescentphaseareoflowfrequency and amplitude and are poorly coordinated; these are commonlyreferredtoasBraxton-Hicks contractions inwomen. Uterine stretch has been shown in animal models to increase gap junctions and contraction-associatedproteinsinthemyometrium. The concept of a role for the fetal lung in the initiation of parturition is particularly attractive because the fetal lung is the last major organ to mature. Phase2involvesaprogressive cascade of events leading to a common pathway of parturition,andinvolvinguterinecontractility,cervical ripening, and decidual/fetal membrane activation. For most of pregnancy, uterine quiescence is maintained by the action of progesterone. At the end of pregnancy in most mammals, maternal progesterone levelsfallandestrogenlevelsrise. Inhumanandnonhuman primate pregnancies, the concentrations of progesteroneandestrogenscontinuetorisethroughout pregnancy until delivery of the placenta. Functional progesterone withdrawal results in functional estrogen predominance, in part as a result of the increase in placental production of estrogen. The progressive cascade of biological processes leads to a common pathway of parturition, involving cervical ripening, uterine contractility, and decidual/ fetalmembraneactivation. Cervical ripening is largely mediated by the actions of prostaglandins, uterine contractility by the actions of gap junctions and myosin light-chain kinase, and decidual/fetal membrane activation by the actions of enzymes such as metalloproteinases, which ultimately lead to rupture ofthemembranes. During expulsion of the fetus, there is a dramatic increase in the release of maternal oxytocin which facilitates the initiation of the final phase of labor. Uterinecontractionisessentialtopreventbleedingfromlargevenous sinusesthatareexposedafterdeliveryoftheplacenta, and is primarily effected by oxytocin. Themechanismsforthese changesaresecondarytoelevationsintheproductionof aldosterone, prostaglandins, atrial natriuretic peptide, and nitric oxide that reduce arterial vascular tone. This is followed by formation of arterial-venous shunts, due to invasion of the trophoblasts into the maternal spiral arteries.
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