Pedro R.Moreno, MD

• Director, Interventional Cardiology Research
• Mount Sinai Hospital
• Associate Professor
• Department of Medicine
• Mount Sinai School of Medicine
• New York, New York

The homeopathic doctor essential oils plus counselling has suggested was free to change remedies anxiety kids buy generic prozac line, dosages or potencies benefits of counselling and tactile contact but if required by the reaction or a new case-picture no benefit from addition of essential oils anxiety burning sensation buy prozac 40 mg overnight delivery. Based on the observations that a few atopic patients treated with Nitrazepan is a widely used benzodiazepine drug for ranitidine for gastric ulcer have improved depression test auf deutsch buy generic prozac on line, Veien night-time sedation depression testosterone levels generic prozac 10 mg with visa. An infrared video A potent topical steroid cream (beta-methasone camera to identify bouts of scratching lasting more valerate) and lubricating ointment to be used on than 5 seconds was used to calculate the percentage the hands only was permitted throughout the trial depression test for elderly generic 10 mg prozac with mastercard. Frequency of bouts group receiving ranitidine and a topical steroid of scratching was slightly less in the nitrazepan group depression test diagnosis buy prozac now, compared with a reduction from a mean of 10. Seventeen out of the 23 patients titis did not change during the 2 weeks of the study. Although no adverse effects were mentioned in the results section, the authors comment that none of Harms the patients experienced any rebound insomnia or No adverse effects from either ranitidine or residual sedative effect following the nitrazepan tablet. Comment Comment this very small study lacks power to exclude Although most trials of hand eczema had to be moderate-to-small treatment benefits of nitrazepan, excluded from this report because the nature of though there was no indication of any benefit in the eczema was unspecified, this study provides a the patients studied. The most interesting thing clear description to indicate that those included about the study was the novel method use to assess probably had atopic eczema as the sole cause for nocturnal itch, though it remains to be seen their hand dermatitis. Although the method of whether this objective measure is a good predictor randomisation, concealment and degree of success of general eczema improvement as measured by of blinding is unclear, the intention-to-treat analysis validated scales or patient-evaluated measures. The proportion of patients cleared or markedly alleviated (a combined physician/ patient score) and other composite scoring Ranitidine methods suggest a modest benefit of ranitidine in this subgroup of adult atopic eczema patients. Baseline redness to test the importance of the -adrenergenic theory score for patients on salbutamol ointment was 22 in atopic eczema, Ruzicka324 conducted a small at the beginning and this decreased by 9. Benefits Fourteen adults were included in the study, 12 of Harms whom were evaluable at the end of 2 weeks. They There were five withdrawals with three due to took either 300 mg of a theophylline/ethylene- adverse effects. Tremor was reported by five diamine preparation or identical placebo tablets patients taking oral salbutamol and in one patient daily in addition to antihistamines. Some degree of the 2-week period, the mean number of antihista- systemic absorption of salbutamol ointment was mine tablets used by the patients was 1. No intention-to-treat analysis No other differences were statistically significant. Although the statistically significant improvement in redness in those taking salbutamol Harms has been highlighted, this was not declared as a main No adverse effects were mentioned in this study, outcome measure out of the six outcome measures but theophylline is a drug with a narrow thera- beforehand, and could probably be explained by peutic range which can result in cardiac toxicity. Although no Comment clinically useful benefits of salbutamol ointment Methodological details of this short report are scanty. It is difficult to exclude any possible benefit of theophylline on the basis of this study. Papaverine Papaverine is a naturally occurring compound Salbutamol found in opium but lacking in the narcotic activity. It is a potent inhibitor of the enzyme phospho- Based on previous animal studies, which demon- diesterase and it is this property that provides a strated that the 2-adrenoceptor agonist salbutamol possible beneficial action for atopic eczema. Shupack and colleagues327 of a similar small placebo- controlled crossover trial of oral papaverine hydro- Benefits chloride in the treatment of atopic eczema. Itching, number of affected zones, skin thickening, vesiculation, epidermal change and redness were Benefits recorded as outcomes and none of these showed In the Berth-Jones and Graham-Brown study, 110 any clinically useful or statistically significant 50 patients with a mean age of 25. All patients had moderate- reduce the possible bias associated with the to-severe atopic eczema and were allowed to reporting of such open studies. The abnormal liver continue with emollients, a bath oil and a topical function tests in the Schupack study are also a steroid preparation throughout the trial. Of the 45 evaluable patients, mean itch score in the last 7 days of each treatment It has been suggested that a rebound phenomenon period was 58. Baseline that evaluated the role of an anti-allergic medication scores were not presented in the papers. Topical called suplatast tosilate (which down-regulates steroid usage was very similar between the two groups. Of the 20 (out of 30) patients to either bufexamace ointment (a non-steroidal anti- who completed both phases of the crossover, no inflammatory ointment) or bufexamace ointment statistically significant advantage over placebo for and oral suplatast tosilate (400 mg/day). In the any of the parameters of itching, physicians and control group, 15 patients experienced the rebound patients global evaluation were reported. Apart phenomenon after 2 weeks compared with only from non-significant p-values, the actual data for two of 17 patients in the active group (rebound these changes were not presented in the paper. Harms No serious adverse effects were reported in the Harms Berth-Jones study and symptoms such as tiredness No adverse effects were reported in this small study. In the Shupack study, however, three of the study patients on active treat- Comment ment developed abnormal liver function tests, which the issue of rebound from regular use of topical were not due to infectious hepatitis. Nausea occur- steroids is a serious and important one as it is red in 46% of patients on papaverine compared possible that the regular use of corticosteroids with 27% on placebo, though this difference was increases the chronicity of disease while benefiting not statistically significant. This small study was unblinded (the control group did not have an Comment oral placebo) and the rebound was completely the method of randomisation in both of these undefined and therefore highly prone to investi- studies was unclear as was concealment of gator bias. Drop-out rates were randomised, controlled double-blind trial over a modest in both studies and no intention-to-treat long period with clinical outcomes and a vehicle- analysis was performed. Thus in the section on emollients, there are at least ten important unanswered questions remaining. Thus, combinations of treat- in the commentaries in the results chapters, ments such as emollients, topical steroids and rather than as a comprehensive blueprint of education should be evaluated together rather unanswered questions for future primary and than in isolation (Meredith B, personal oral secondary research. In terms of a reference energy needs to be directed at prevention as well as standard for published studies, we compared the treatment of established cases with pharmaceutical results of handsearching the entire contents of agents that at best only control symptoms. Clinical and Experimental Dermatology for atopic eczema trials and those with our electronic searching. Diagnostic tests None of the five controlled trials had been missed Although diagnostic tests are not regarded strictly as by our searching methods. Ideally the benefit of such independent search by members of the Cochrane testing, which has considerable time and health costs Skin Group (Diepgen P, personal oral commun- if applied to all atopic eczema sufferers, needs to be ication, 2000). This will reduce antihistamines than a recently published systematic selection bias and will also permit evaluation of review of antihistamines in atopic eczema. This applies to the lucrative high-street the authors also suspect that there is a large body industry of performing allergy tests on vulnerable of unpublished data held by pharmaceutical comp- atopic eczema sufferers in addition to the more anies for various reasons. It is likely that Horizon scanning more negative studies fall into these categories. It is likely that the next 5 years will witness an Estimating the magnitude of this hidden part of the increase in the number of topical pharmaceutical iceberg of evidence is difficult without additional agents for treatment of atopic eczema. In the field of evaluating evening primrose ments such as tacrolimus and ascomycin derivatives oil for instance, two of the authors of the current are already well down the road to development report were commissioned by the Department of and evaluation, and others such as cytokines Health in 1997 to conduct a meta-analysis of all and phosphodiestarase inhibitors are following. Sadly, permission to publish this report has Two recent review articles have considered never been granted, but it did contain the results future developments. Despite writing to the company for any unpublished data for this report, Validity and robustness of results no data have been forthcoming to date (Tables 39 and 40). Schering Healthcare have recently signed-up to Health Technology Assessment 2000; Vol. Berberian 1999 and Drake 1994 already included both trials on file It is for these reasons that future pragmatic trials should be considered in primary care. Those making Schering Healthcare Yes None on file treatment guidelines or recommendations based on the results of this report are therefore advised Typharm No to update their conclusions with further searches. Phyto pharmaceuticals Yes Those topic areas that will be taken forward as Cochrane Reviews will be updated automatically as Squibb No part of the Cochrane Collaboration process. Many benefit of psychological and various non-pharma- newly developed and potentially toxic drugs such cological approaches. For most people, atopic eczema is a chronic inter- Quality of reporting mittent disease, and studies that evaluate numbers Quality of reporting was generally very poor in of relapses and duration of symptom-free periods most of the studies. Our primary quality criteria of are required in addition to studies that measure a clear description of generation of the random- short-term reduction in clinical signs. These features have been shown to lead or vehicle effect in atopic eczema can itself account to biased estimates of treatment effects. This is akin to throwing a dart and Given such a range of outcome measures and drawing a dartboard around it. This is not necessarily a to a scale simply meant that it had been used problem providing they have been interpreted before. Duplicate publication was also former is objective and the latter is subjective. Yet the variability of the objective measures is often more than patients symptoms, and their the situation has probably improved over the past repeatability between physicians is often poor. These changes alongside the physician-based scales, and use of probably reflect a change in standards of clinical scales should be restricted to a few well-tested ones 118 trial reporting in larger journals. This type of research is important the arm of treatment is to control symptoms, improve when extrapolating from cost-effectiveness studies quality of life for patient and family, or to clear the of motivated patients in secondary care to a entire rash (which may be unrealistic at present). It may be the case that an inexpensive single treatment delivered with a Crossover designs simple package of care may be more effective than Although the efficiency in terms of reduced numbers an expensive therapy without any such support. Data from the second half of a crossover six most urgent research themes are shown in study may have to be discarded in the presence of Table 42. Studies on disease prevention also need a period or carry-over effect, though this has rarely to be considered. Left/right body or limb comparisons are also popular but introduce Secondary research problems with blinding and systemic absorption. Further research, such topical corticosteroids suggests that different as the current research by this team to identify a inflammatory diseases respond differently to the simple list of patient-derived outcome measures same treatment. A recent review32 of need to be separated from patients with other named outcome scales used in atopic eczema inflammatory dermatoses, or at least their results identified 13 different instruments, none of which should be presented separately. In addition to completing the validity testing of such named scales, further Future research priorities research involving consumers and carers is required to determine a minimum list of similar Primary research outcome measures, for example a quality-of-life With such glaring gaps in our current knowledge measure, patient-rated global disease improvement about the effectiveness of treatments for atopic and the best of the current named objective eczema, it is difficult to know where to start in doctor-rated scales for use in future atopic eczema recommending research priorities. This will vastly aid the comparability of avoid bias on behalf of the authors choosing just studies providing such a list has been derived using what they think is important in future primary the best quality external evidence with ownership research, results of the survey of 25 researchers from a wide range of stakeholders. Drug regulatory and clinicians with an interest in atopic eczema authorities could occupy a key role in recom- and six consumers with atopic eczema are shown in mending the use of such measures. Research themes fall mainly into opportunity to explore more generic issues such as assessing the things that we already have rather the relationship between magnitude of benefit and than assessing the role of newer agents. Role of maternal dietary manipulation and house dust mite avoidance Emollients Does regular use of emollients reduce disease relapse Are the newer once-daily topical steroids more effective than older preparations Tacrolimus and How do the newer topical agents such as tacrolimus and ascomycin compare with topical corticosteroids Diets Role of exclusion diets Factors affecting Do different patterns of atopic eczema (discoid, reverse pattern, flexural) require different treatments Treatments for How does ultraviolet treatment compare with oral immunomodulatory treatment in severe disease Efficacy of agents such as azathioprine, methotrexate, anti-leukotrienes, naltrexone Disease dimensions What are the most effective interventions at reducing the itch of atopic eczema Does any treatment alter the natural history of disease if used properly and for long enough The role of tests What is the usefulness of allergy tests in disease management What is the role of allergic contact dermatitis in topic eczema Psychological Which are the most psychological/psychotherapeutic approaches and how well do patients respond to such approaches outside approaches the hands of enthusiasts Bandages How effective are wet-wraps, with and without emollients or topical steroids Organisation of How effective are educational approaches in improving the correct use of first-line treatments How effective is a multiprofessional team approach compared with a dermatologist alone Modifiable environmental factor What is the role of specialist nurses in managing patients with atopic Some observational evidence of benefit in some centres. In other areas where there is a multi- interventions and these could perhaps be looked at plicity of new interventions being introduced carefully in terms of the rationale for their constantly, consideration should be given to more continued widespread use. This is easier said than flexible and pragmatic approaches such as the use done as advice such as avoidance of synthetic fibres of tracker studies. Implications for healthcare Similarly, use of twice-daily topical corticosteroids or dilutions of topical corticosteroids have also the strength of evidence supporting the various become deeply embedded in clinical practice. The strength of effects and cost also have to be taken into account evidence in relation to those interventions which when making recommendations. Given the virtual absence Trying to split Table 43 into further first-line, of long-term studies, the data can only refer to second-line and third-line treatment guidelines is short-term control of disease. Decision analysis approaches ination of the original studies in the context of local should also be used to determine which inter- guideline and policy development. Therefore it might be often not answered the questions of most entirely reasonable to continue to use a range of importance to patients and their carers. Great Ormond Street); Professor Peter Friedmann, (Southampton); Dr J Berth-Jones, (Coventry); Hywel Williams wrote the study proposal, super- Dr S Lewis-Jones (Dundee); Dr J Vesty (Sunder- vised the day-to-day running of the project, hand- land); Dr D Paige (Royal London Hospital); searched conference proceedings, checked on Professor A Taieb (Bordeaux); Dr C T Kennedy excluded studies, abstracted and summarised data (Bristol); Dr M R Judge (Bolton); Dr R Chalmers from most of the included studies, and wrote the (Manchester); Dr J D Wilkinson (Amersham); final report with help from Colette Hoare. Professor Thomas Diepgen (Heidelberg); Professor John Harper (London); Dr David Atherton the authors wish to thank the following people for (London); Dr Tom Poyner (Stockton-on-Tees); their helpful contribution to this report: Dr Mary Glover (London); Professor Mark Lebwohol (New York); colleagues of the late Searching Professor Hjorth; Professor Toshi Aoki (Osaka); Dr Finola Delamere, Trials Search Co-ordinator, Professor Frederik Bahmer (Germany); Dr Kenji Cochrane Skin Group, Nottingham; Dr Carole Nishioka (Japan). Mr David Potter, Mr Jack Stein, Mr John Fulton, Professor Vladimir Vlassov (Moscow) for translation Mrs Margaret Newton, Ms Barbara Meredith, of Russian articles.

These Most patients with sleep related eating disorders have histo- activities may represent reenactment of previous abuse situations; ries of other parasomnias (isolated sleepwalking mood disorders in children generic prozac 40mg visa, enuresis depression definition et synonyme generic prozac 60 mg line, sleep there is amnesia for the behavior on the following day unipolar depression definition purchase prozac 40mg line. The age of terrors depression music discount prozac 20mg on-line, or some combination of these) depression gene cheap prozac 40mg with visa, and more than one-third onset can range from childhood to middle adulthood mood disorder journal articles discount prozac online. Other para- had a daytime eating disorder (bulimia nervosa, anorexia nervosa, somnias, particularly disorders of arousal described earlier, must or binge eating disorder). Polysomnography has shown that catathrenia is associ- (eating at night with full alertness), binge-eating disorder or ated with a slightly decreased heart rate and moderately positive bulimia nervosa with nocturnal eating (eating at night with full intra-esophageal pressure. The groaning ends in a snort, followed alertness, combined with a daytime eating disorder), dissociative by rebound in heart rate. While catathrenia may have an adverse impact on disorder, posttraumatic stress disorder), and Kleine-Levin Syn- 87 social and familial function, no specific therapy has been found drome. Clinicians should be aware that ing behavior (such as eating larger amounts of food), depressed many pediatric parasomnias are benign, self-limited, and may mood, irritability, and hypersexuality (as well as other compulsive not persist into late childhood or adolescence. Onset is often during adolescence, more commonly childhood often differ in type from adults (e. Figure 2: Evaluating and Treating Pediatric Parasomnias92 the moaning/groaning sounds are in helpful. Dx: arousal parasomnias Dx: Nocturnal enuresis - Sleepwalking - Sleep terrors Yes No - Confusional arousals Combative or Evaluation: violent The further study of parasom- 2004;2:14 nias in children may help elucidate the multifactorial etiologies 21. On the reported association of psy- of these fascinating conditions, shedding light on their potential chopathology with sleep terrors in adults. Westchester, Illinois: American Acad- 2002;19:522-534 emy of Sleep Medicine, 2005 27. Autosomal dominant nocturnal ing, and confusional arousals in the general population: their fre- frontal lobe epilepsy in a Spanish family with a Ser252Phe mutation quency and relationship to other sleep and mental disorders. Prevalence and genet- 1988;297:592 ics of sleepwalking: a population-based twin study. The use of sched- 1997;48:177-181 uled awakenings to eliminate childhood sleepwalking. The role of sleep and the activity profile within frontal and parietal cortices: a sleep disorder center in evaluating sleep violence. Nightmares and dissociative possible indicator for alpha-synucleinopathy demonstrated by dopa- experiences: the key role of childhood traumatic events. Clinical importance of night- 2004;251:781-794 mare disorder in patients with dissociative disorders. A sensorimotor approach to the treatment sleep behavior disorder in neurologic disorders: results in 14 pa- of trauma and dissociation. Exploding head syndrome and idiopathic stabbing ior disorder in 33 polysomnographically confirmed cases. Status dissociatus-a perspective on graphic recordings and therapeutic suggestions. Clinical and polysomnographic features of sleep- pathologic associations of sleep paralysis in the general population. Catathrenia (nocturnal groan- ial aggregation and association with psychiatric disorders in a na- ing): a new type of parasomnia. Development of disturbing dreams during adolescence and their relation to anxiety symptoms. Treatment of chronic nightmares in adjudicated adolescent girls in a residential facility. This document will continue to be periodically updated to reflect the growing body of literature related to this topic. Be familiar with various catheter types (including standard 2-way and 3-way urethral Foleys). Be familiar with prevention and initial management of traumatic catheter removals. Understand advantages/disadvantages of suprapubic tubes and the standard procedure for their replacement. Introduction: the two fundamental purposes of the bladder are to store and empty urine. If a person is unable to empty his or her bladder, significant sequelae will result, including but not limited to suprapubic pain/discomfort, hydronephrosis, renal insufficiency, bladder damage and infection. In settings of urinary retention, obstruction can be relieved with simple drainage of the bladder; this can be accomplished in various ways, all of which must take into account the particular patients presenting history and clinical situation. Iatrogenic and patient initiated bladder catheterization injuries are a source of significant cost and patient morbidity. Understanding fundamental concepts behind bladder drainage gives the provider the ability to safely manage what can sometimes be an urgent patient care issue. Indications for Foley Catheter Placement Knowing when to place a Foley catheter is just as important as utilizing proper technique for its insertion. Careful patient selection is paramount because catheter placement can be associated with urethral trauma and complications, as we will discuss in ensuing sections. Of note, placement of an indwelling catheter is different from a straight catheterization procedure; the latter involves a catheter that is inserted and then removed for transient decompression and drainage of the bladder or to obtain a clean-catheterized urine specimen. In contrast, an indwelling Foley catheter is semi-permanent to allow for continuous, passive urinary drainage. In general, candidates for an indwelling Foley catheter have the following conditions/ presentations as listed below. It is usually caused by prostatic enlargement, outflow obstruction such as from strictures, or atonic bladder disorders. When present, bilateral hydronephrosis is frequently associated with chronic urinary retention. These patients often require a 3-Way Foley catheter, which allows for continuous bladder irrigation with simultaneous drainage. Contraindications to Foley Catheter Placement: Urethral catheter placement is absolutely contraindicated in cases of known or suspected urethral injury, such as in the setting of a pelvic fracture. On physical exam, gross hematuria, blood at the urethral meatus, perineal ecchymosis, and a high-riding prostate on digital rectal exam are signs that are associated with urethral trauma. A retrograde urethrogram should be performed in these cases prior to any attempt at urethral catheterization. A relative contraindication would be the presence of an artificial urinary sphincter which would need to be deactivated prior to any attempts at urethral catheterization. The most common contraindication to Foley catheter placement is actually not having an adequate indication for its insertion in the first place. For example, urinary incontinence by itself is not considered an adequate indication for a Foley catheter in most cases. The Different Catheter Types Catheters come in sizes that measure the outside circumference in mm. The French size, as well as the recommended filling volume of the catheters retention balloon (in cc or mL), is listed on the plastic cuff of the catheter sidearm (the arm of the Foley where the balloon is inflated). A typical catheter size for an adult patient is 14, 16, or 18 Fr with an associated 5 or 10 cc balloon. Straight Catheters- this is a traditional simple catheter, and often the type that is provided within in-patient catheter insertion kits. Most catheters are made of silicone or latex but some straight catheters are also made from vinyl which tends to be stiffer and more rigid. This is also the type of catheter used for intermittent self-catheterizations and for urethral self-dilations that some patients are asked to perform periodically for urethral strictures. Coude Catheters- Coude is French for the word elbow, which is used to describe the curved tip of this catheter. For many, a 16 or 18 Fr coude catheter is the go-to catheter in men with a known history of benign prostatic hypertrophy or any history of prostatic surgery. The hematuria catheter tends to be more rigid and some even have metal coils spanning the catheters circumference to tent open the lumen and facilitate hand irrigation of clots when required. These hematuria catheters also come in larger sizes (22-24 Fr) to prevent obstructions from blood clots; and they have larger associated balloons (approximately 30 cc) to allow for tamponade of the prostate when the catheter is placed on traction. In general, hematuria catheters are used when a patient has significant gross hematuria that cannot be easily cleared with hand irrigation alone. The initiation of continuous bladder irrigation, usually in the form of normal saline, requires close monitoring to ensure inputs and outputs are roughly equivalent. Suprapubic Tubes- these urinary drainage catheters require the percutaneous placement of a Foley or similar catheter through the lower abdominal wall directly into the bladder. Although it involves a surgical procedure, placement of a suprapubic tube is often preferred in situations where urethral catheterization is difficult or impossible, or if the patient requires a permanent indwelling Foley. Suprapubic tubes are generally more comfortable for male patients than urethral Foley catheters and are easier to change in patients with contractures and other bodily deformities. Standard Technique for Adult Foley Catheter Placement: Standard sterile technique for placing a Foley catheter involves the following steps: 1. You may use non-sterile gloves for this preliminary cleaning and to reduce the foreskin in an uncircumcised male. Start with laying a sterile sheet between their legs and putting on an overlying cover drape with a hole in it, which is centered on the external genitalia. For example, open and place the lubricant on the sterile field so it is accessible to the catheter. Do not use an antiseptic prep to which the patient has a known allergy and use only pure silicone catheters for patients with latex sensitivity. With your non-dominant hand, part the labia in a woman or pull up on the phallus of a male. From this point on, all catheter insertion activities will be done with just one hand. With your dominant hand, clean off the urethral meatus with betadine or the antiseptic cleaning agent provided. Wipe from high to low in a woman; in a male, start at the meatus and, with a circular clockwise/counterclockwise motion, extend the wiping outwards and down the shaft. Do not let go of the penile shaft with your non-dominant hand until the catheter has been completely advanced into the bladder. Coat the tip of the catheter with sterile lubricant and advance the tip of the catheter into the meatus. It is helpful to initially hold the phallus relatively perpendicular to the patients body and then angle the penis downward towards the feet after the catheter has traversed the pendulous urethra. Most of the time, this can be managed by slow, steady pressure and gently rotating the catheter right and left until the tissues relax and the catheter can pass. If there is no urine return, irrigate the catheter using a catheter-tip syringe and 50-60 cc of sterile water or normal saline. Never inflate the catheter balloon until you have confirmation the tip of the catheter is in the patients bladder. We do not use normal saline to inflate the catheter balloon, as salt crystals could theoretically precipitate in the balloon, valve or balloon channel making deflation of the balloon difficult when removing or replacing the Foley. If there is strong resistance to balloon inflation or if the patient indicates pain, stop and check the position of the Foley. This can be done clinically by catheter repositioning or by irrigation of the drainage port. If there is no urine return, and the catheter is inserted to the hub, irrigate the catheter lumen with normal saline (as this is safer than sterile water if it extravasates). If you cannot move the catheter even a little, the balloon could be in the prostate or pendulous urethra. Failure to do this could lead to paraphimosis, a painful surgical emergency condition. The New England Journal of Medicine has free public access videos on standard sterile male and female catheter insertion that are very helpful and follow the same procedure as outlined above. Managing Difficult Foley Catheterizations There are several potential problem areas when attempting to place a Foley catheter that can present difficulties, but there are simple solutions to most of these problems which are outlined below. Finding the Urethral Meatus: Female Identification of the female urethral opening can be troublesome at times due to body habitus, morbid obesity, atrophic vaginitis and retraction of the urethral opening into a tight vaginal introitus. Obesity and body habitus issues can be overcome by the use of Trendelenburg positioning, good lighting and having sufficient help to provide elevation and exposure of the vaginal area. In many cases, just painting the vaginal area with antiseptic will cause a brief winking of the urethral opening which identifies it for catheterization. In some elderly ladies, the urethral meatus has retracted into the vagina which is now too tight for a speculum and the opening cannot be directly visualized. It will still be at the 12 oclock position in the vagina and will feel like a button-hole in your lab coat. A coude catheter facing upwards can then be directed at this opening by touch alone. Finding the Urethral Meatus: Male 5 In some obese men, a buried penis may seem a difficult obstacle but this can usually be managed by having an assistant press hard downwards with both hands around the base of the penis. This will depress the fat and subcutaneous tissue exposing the penis for catheterization. Difficulty in locating the urethral meatus in males is typically from either edema or severe phimosis. Edema can be significantly reduced by continuous manual pressure for about 20 minutes or, preferably, by wrapping a thin (1 inch) elastic Ace wrap or similar over a gauze pad around the penis for a similar period. This continuous pressure gradually reduces swelling and edema allowing for better visualization.

If too much on the degree of retraction mood disorder 6 gameplay order prozac, sof-tissue expan- product is injected into this area utter depression definition order prozac paypal, the nasofron- sion should be handled in more than one ses- tal angle may become too shallow depression definition en francais cheap 60 mg prozac mastercard, producing an sion depression symptoms messy house generic prozac 20 mg without prescription. It produces a delicate ap- pearance of the nose the Most Common Indications Chapter 5 49 footplates of the medial crura may increase tip projection (Fig anxiety zone symptoms generic 10 mg prozac visa. Filling into this point may cause supratip deformation and consequent dropping of the na- sal tip (Fig mood disorder education day purchase 20 mg prozac overnight delivery. To enhance the supratip break, there must be a diference in height between the domes and the septal angle; a tiny injection into the tip of the dome may produce this efect. An increase in tip rotation is conducted in patients with a re- duced nasolabial angle. Increasing the nasal tip projection may be undertaken by direct injection into the domes (Fig. When treating the tip, it must be established whether the patient needs augmentation of the domes and/or the middle crura. When only the domes need augmentation, injections must only be made into the upper por- tion of the tip. This is a nice solution for patients with thin skin who present surface irregularities on the tip. A deli- cate caudal injection into the tip may produce an increase in tip projection and a nice upwards tip rotation. When a major increase in tip projection is necessary, flling into the sof tissue of the pre- maxilla is advisable. Fillers may be an important ally to prepare patients for surgery, or may even be the only treatment 5. Only experienced phy- tip height helps to give an idea of the quantity sicians should handle nonbiodegradable prod- of product to be injected. Even some experienced physicians only use with the nasofrontal angle to reduce its concav- biodegradable products to avoid complications. Hyaluronic acid enables a good start, although The dorsal augmentation should almost reach the results may not last too long. In- drophilic properties and pseudoplasticity, it can jections should be carried out with a retrograde be easily molded. Nonbiodegradable products are a good choice A dorsal hump is treated mainly by surgery. Afer a 5-min procedure, the patient could leave the ofce with no postoperative period, no ecchy- mosis, and no bandages 5. If a are not willing or are unable to submit to surgical fller is inadvertently injected into a blood ves- procedures. Excessive flling of the cartilaginous dorsum may lead to supratip deformation and irregu- larities. The nasofrontal angle and the nasola- bial angle rarely produce deformities if properly injected. If too much product is injected into the tip of the nose, a boxy deformation may occur. General complications such as swelling, red- ness, pain, and ecchymosis may also occur with fllers. Strong muscular tonus might lead to very deep Nasolabial folds are one of the major indications wrinkles at quite an early age (Fig. Each of these folds requires special attention with regard to the in- The nasolabial folds must be analyzed prior to jection technique used, the material to used, and fller injection. In older patients with very deep folds, for example, it might be necessary to inject up to 2 ml per site. The best results are obtained in patients with either no or mild saggy skin over the nasolabial fold. Nasolabial folds are quite easy and fast to treat with the retrograde injection technique. Deep and superfcial naso- increased by contracting the levator labii superi- labial folds might require a multilevel approach. Both muscles are activated when pa- may be atrophic and the fller may go down, in- the Most Common Indications Chapter 5 53 stead of lifing the fold, a multilevel approach is using the same injection punctures to decrease recommended. Diferent fllers with difernt properties might be combined to optimise the results (Figs. The sausage: the sausage constitutes the re- mains of a fller that was too superfcially in- jected. The lump: injecting large amounts of a fller will result in fller depots that might be pal- pable for several weeks. An injection administered to a patient in a prone position might lead to insufcient correction. Always inject a bit medially to avoid an increase in the depth of the treated folds. When the fller is injected into diferent levels of the dermis (the multilevel injec- Fig. A wide spectrum of emotions is represented by the lips, from happiness to sadness and sorrow. When the sphincter The lips cover more than the area of the red mechanism is intact normal lip function pro- part of the mouth. They also include the skin motes a competent oral seal for liquids and sol- adjacent to the red part of the mouth. The free movable na- be considered as an anatomic unit with exten- ture of the vermillion and cutaneous skin makes sions superior to the nose and inferior to the this area quite suitable for distortion. The ratio between the upper and lower desire lip augmentation and present with pre- lips, at golden proportions, is 1:1. With aging, the mouth A very important topographic landmark is the may present with perioral radial grooves and a philtrum. Lip reshap- lip is highlighted by the two vertically oriented ing will not only require augmentation, but also ridges of the philtrum. The lack of additional support incisors) are inclined backwards, lip projection at this level and excess of muscular movement is extremely difcult and sometimes impossible. During the smile, there The major muscle of the lips is the orbicularis may be excessive inversion of the vermillion, oris muscle. Fillers are responsible for the sphincter function of the may not produce the desired efect in this case. Patients must be evaluated in lips, producing complex movements during nor- both static and dynamic situations. The levators lie from medial to lat- least four diferent types of smile, and dynamic eral: the labii superioris alaeque nasi levator, the asymmetries are very common and should be labii superioris levator, the zygomatic minor and demonstrated to the patient beforehand. The depressors include the depressor anguli oris, the depressor labii inferioris, and the mentalis muscles. Both of these are branch- To avoid imperfect results or the necessity for es of the facial artery. The motor in- infraorbital nerve must be injected followed by nervation of the orbicularis oris is provided by infltration of lidocaine in the submucosa lat- the buccal branches of the facial nerve. Serial techniques increase approach is generally preferable as it is usually bleeding and may lead to irregular flling. Nevertheless, in some frame of the lips (the white line) should be in- patients topical anesthesia alone, or even ice bags jected frst; this will help to limit the expansion may be acceptable. Because of its for instance, the vermillion is then augmented molecular resistance, collagen injected into the with hyaluronic acid. Attention must be paid to white line is the preferable choice for this area the dental arcade at this time. For the vermillion, hyaluronic acid is desired, the medial tubercle may be flled ei- gives the volume and the mobility that only ther from the mucosa or intraorally through the this highly hydrophilic substance may provide submucosa (Fig. Care should be taken direct injection into each small rhytide should not to inject them too superfcially or lump for- be performed (Fig. In senile lips, a nicer look will be achieved if Afer proper anesthesia, injections may be the entire lip structure is treated (Fig. If the started from Cupids bow or from the oral com- lips are surrounded by elastotic skin, combina- missure. It is most important to perform it as a tions of injectable fllers are recommended with the Most Common Indications Chapter 5 59 ablative methods, such as chemical peels or la- ser resurfacing. The best results are obtained in those patients whose anatomic landmarks are preserved and who have sof, distensible skin. Swelling, ecchymosis, and redness are very common and are dependent on the type of product, quantity of material injected, and the Fig. Nonbiodegradable products are those more ofen found to be associated with complications. Due to the intrinsic mobility of the lips, any capsule formation may provoke un- natural and quite obvious results. Sometimes pa- tients ask for more material and we should show them how they would look in a photo before go- ing any further. In older patients with increased elas- actively pronounced when the patient forms an tosis, a very deep injection may have little efect I (Fig. If the results are not as perfect as desired following the tun- Patients with sagging corners of the mouth as nel technique the area should be treated with the well as patients with manifest lines are suitable multiple-point injection technique to improve for treatment. In patients with increased elasto- sis, this multilayer technique will provide the best results and help to prevent unwanted deep 5. The most appropriate fller must be chosen according to the depth of the lines, wrin- kles, or folds. Tese techniques will hand, may have heavier features and should have help to blend the fller better in the surrounding a stronger chin. In all cases, a youthful and clean area and avoid the appearance of an unnatural el- jawline is desired. Despite the scientifc studies concerning the As for nasolabial folds, it is advisable to inject the safety of the use of silicone prostheses for chin fller medial to the fold; a more lateral injection augmentation, some patients simply refuse to be technique would increase the visibility of the fold submitted to it. Patients prefer minor and mini- the Most Common Indications Chapter 5 61 mally invasive procedures, although some doc- tors would indicate more complex procedures such as chin advancement. Patients may accept limited results with fllers rather than submitting to cranial surgery. The midlateral zone can be defned as the region extending from the mental foramen pos- Fig. The submental area is located under the chin between the pla- greater auricular nerve is in the cervical fascia, tysmal band and above the cervicomental angle. The men- The most suitable skin for chin and mandible tal nerve exits from the mental foramen, below reshaping is that which is sof and has mild at- the second mandibular premolar. It tients, there may also be sof-tissue atrophy later- becomes progressively looser and more mobile al to the anterior chin, producing a deep triangle lateral to the cheek and caudal to the neck. The contraction of the mentalis muscle pro- With the increase of the jowl pad and sof tis- duces protrusion of the lower lip. This muscle sue atrophy, marionette lines and a sad mouth arises from the mandible below the central and develop. The migration of fat down to the man- lateral incisors and inserts into the skin of the dible creates the jowls that may extend below the chin. The mandibular branch of the facial nerve passes just The ideal relationship in a patients face is one- anterior to the middle portion of the mandible third upper lip and two-thirds lower lip and into the midlateral zone. Patients with mandibular hypoplasia ap- the facial nerve has a variable course but its loca- pear to have a round face due to a short lower tion is normally at the angle of the mandible. On the profle tance between the mandible tip and the lip, thus examination, the face presents a convex appear- balancing the face. Fillers are also suitable as a ance, jowls, and obtuse mentocervical angle with pretreatment before surgery to give an idea of redundant skin. In Fillers may be placed in the central segment alone, some cases, avoiding extensive orthognathic sur- between the mental foramina and along the man- gery means giving fllers a try, while understand- dible body. When the central mentum and the ing their limitations and the number of sessions midlateral zone is augmented, there is a resulting involved to obtain a nice result. Fillers The classic mandibular retrognathia patient in the mandibular angle will either widen or elon- presents with a retruded mandible and convex gate the posterior mandibular angle, promoting a sof tissue profles. Tese patients are ideal of the mandible area associated with the nasola- candidates for fllers in these areas. Fillers will bial fold may promote an interesting result, espe- improve chin projection and promote a jawline cially among patients who do not desire a surgi- reshape. Some patients may need forward and cal procedure or do not have enough time to be downward projection; flling into the upper and submitted to it. A face-lif efect may be obtained lower part of the menton may increase the dis- (Fig. It is useful both as a single treatment or for surgi- cal planning Depending on the physical examination, pa- 5. If the In contrast to surgical procedures with implants, patient is older, the presence of jowls of mild de- there is no bone resorption, no fstula, no nerve gree can be improved with the injection of the damage, and rarely any extrusion or nodule for- triangle reaching from the mental foramen to the mation. This area may mal projection, even in patients with adequate not be easily expanded, and the mobility of the sof tissue. Mandibular and chin reshaping with skin at this site must be evaluated prior to start- fllers may only produce mild ecchymosis and ing corrective procedures. The short triangle of sof tissue is generally atrophic and duration of the result is a drawback of the use of this area may be flled because of its mobility. Tat is why patients must Retrograde injection is started by flling along be very well informed about it. Infammatory re- the frame, followed by a sof massage to smooth actions and infections are rare and can also be the surface.

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Clonazepam and felbamate sig- assessed by probe substrates midazolam depression symptoms 11 year old best buy prozac, caffeine anxiety 2 generic prozac 40 mg with amex, and digoxin depression experiments buy prozac online pills. Clin nificantly inhibit valproate metabolism and increase valproate Pharmacol Ther anxiety 40 year old woman prozac 40 mg lowest price. Bidirectional interaction of val- decrease of 25% to 40% in phenytoin serum concentrations proate and lamotrigine in healthy subjects depression of 1893 buy 20mg prozac fast delivery. Pharmacoepidemiologic investiga- tion of unchanged drug (35%) depression photos buy 40 mg prozac visa, metabolism via N-acetylation tion of a clonazepam-carbamazepine interaction by mixed effect modeling (15%), and reduction to 2-sulfamoyolacetylphenol (50%). Oral contraceptives induce study in healthy volunteers of the effect of carbamazepine and oxcar- lamotrigine metabolism: evidence from a double-blind, placebo-controlled bazepine on cyp3a4. Analysis of a clinically impor- mazepine on the pharmacokinetics of an oral contraceptive containing tant interaction between phenytoin and Shankhapushpi, an Ayurvedic norethindrone and ethinyl estradiol in healthy obese and nonobese female preparation. Increase in tiagabine serum and standard antiepileptic drugs in patients with epilepsy. Pharmacokinetic and metabolic inves- type on the steady-state concentration of N-desmethylclobazam. Brain tigation of topiramate disposition in healthy subjects in the absence and in Dev. Stiripentol in severe myoclonic clearance of valproic acid during intake of combined contraceptive steroids epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated in women with epilepsy. Time-course of interaction between carba- valproic acid and recurrence of epileptic seizures during chemotherapy in mazepine and clonazepam in normal man. Influence of phenytoin and pheno- after introduction of efavirenz in a bipolar patient. Lack of pharmacokinetic interaction concentration on lamotrigine pharmacokinetics in developmentally dis- between oxcarbazepine and lamotrigine. To develop a rational approach to the management of indi- viduals who present with an initial unprovoked seizure, it is necessary to have some understanding of the natural history Etiology and prognosis of the disorder in this setting. The remainder will already have a history of symptomatic seizures are those without an immediate cause prior events at the time of presentation. It is the group who but with an identifiable prior brain injury or the presence of a presents with a single seizure that is most relevant to this dis- static encephalopathy such as mental retardation or cerebral cussion. Cryptogenic seizures are those occurring in other- epilepsy, a first unprovoked seizure is defined as a seizure or wise normal individuals with no clear etiology. Until recently, flurry of seizures all occurring within 24 hours in a person cryptogenic seizures were also called idiopathic. In the new older than 1 month of age with no prior history of unpro- classification, idiopathic is reserved for seizures occurring in voked seizures (3). Higher recurrence symptomatic first seizure have higher risk of recurrence than risks are, with one exception (19), reported from studies that those with a cryptogenic first seizure. A meta-analysis of the included subjects who already had recurrent seizures at the studies published up to 1990 found that the relative risk of time of identification and who were, thus, more properly con- recurrence following a remote symptomatic first seizure was sidered to have newly diagnosed epilepsy. Comparable findings are rence risk reported in the different studies, the time course of reported in more recent studies (13,15,21). This is because, the association is not just because nocturnal seizures tend to by definition, to meet the criteria for an idiopathic first occur in certain epilepsy syndromes. Studies of recurrence risk follow- seizure occurred during sleep compared with a 30% risk for ing a first seizure in childhood have uniformly reported that those whose initial seizure occurred while awake (13). From a therapeu- reason, the American Academy of Neurologys recently pub- tic point of view, the implication of a seizure during sleep is lished guideline on the evaluation of children with a first unclear. Hauser and colleagues (8) found that 407 children (38 cryptogenic/idiopathic, 10 remote sympto- generalized spike-and-wave patterns are predictive of recur- matic) presented with status epilepticus (duration longer than rence but not focal spikes. However, if a recurrence did adults as well (5), although which electroencephalographic occur, it was likely to be prolonged (13,29). Of the 24 children patterns besides generalized spike and wave are important with an initial episode of status who experienced a seizure remains unclear (5,9,10,18). In adults, there is a suggestion that a pro- longed first seizure, particularly in remote symptomatic cases, is associated with a higher risk of recurrence (10). Sleep State at Time of First Seizure In adults, seizures that occur at night are associated with a Number of Seizures in 24 Hours higher recurrence risk than those that occur in the daytime (11). Interestingly, prospective studies in both children (13) and adults (30) have Chapter 43: Initiation and Discontinuation of Antiepileptic Drugs 529 found no difference in recurrence risks in patients who present ciated with a differential risk of further seizures once a second with a cluster of seizures in 1 day compared with those who seizure occurs (14). This is not an uncommon event the issue of treatment following a second seizure in children is and occurs in about 25% of cases. Many of these children demiological definition of a cluster as being a single event and have idiopathic self-limited epilepsy syndromes, such as do not suggest an increased risk of further seizures. In addition, the frequency of seizures in this group is low, with only 25% of children who had 2 seizures Treatment Following a First Seizure experiencing 10 or more seizures over a 10-year period (14). Two well-designed prospective studies which part of a benign self-limited syndrome, as well as the fre- randomized subjects to treatment or placebo following a first quency of the seizures and the relative risks and benefits of unprovoked seizure found that treatment reduced the recur- treatment. Exceptionally low the data from randomized clinical trials are increasingly in recurrence rates of 8% to 12% were reported in studies that favor of not routinely treating after a single seizure even in limited subject entry to neurologically normal children with adults. In the past, it was thought that adult-onset epilepsy had a Two studies in adults (9) and children (14) examined what far less favorable prognosis for remission than childhood- happens after a second seizure. In adults, the recurrence risk onset epilepsy, and that withdrawal of medications was after a second seizure is 70%, leading Hauser and coworkers rarely feasible in this population. Four the recurrence risk following a second seizure is also approxi- years after onset, the majority of adults with new-onset mately 70%. Those with a remote symptomatic etiology and seizures will be at least 2 years seizure-free (46,47). Many those whose second seizure occurs within 6 months of the first adults self-discontinue their medications and are still have a higher recurrence risk (14). However, after 2 years, the subsequent reported recurrence risks of less than 20%. These relapse rates must also be con- epilepsy with a relative risk of approximately 1. Interestingly, in a 30-year follow-up study of 178 is a result of the higher risk of recurrence in adolescent-onset patients with epilepsy, there was a slightly higher recurrence seizures (51,73). Two reports showed no differences in recur- two groups were not randomized and were, therefore, not rence risks between children and adults (55,80). In one study, 38% of the subjects had childhood onset but this was defined Clinically, it is important to identify subgroups with better or as onset before 15 years of age (55). Several studies in less favorable prognoses for maintaining seizure remission off children have reported that an age of onset older than 10 or medications. Studies of childhood-onset epilepsy that included adolescents have reported low recurrence risk Etiology and Neurologic Status (50,51,53,59,67,73,74,76,78). Studies of adolescents and adults that have primarily included adolescent-onset cases Patients with remote symptomatic epilepsy associated with a have reported recurrence rates similar to those seen in adults prior neurologic insult, congenital malformation, motor hand- (51,55,65,80). One retrospective study limited to adolescents icap, brain tumor, mental retardation, progressive metabolic with adolescent-onset seizures reported a recurrence rate of disease, trauma, or stroke are less likely to attain complete 49% (71). In one study of similar in studies of both children and adults and is indepen- 264 children and adolescents, the cumulative recurrence risk 2 dent of the absolute recurrence risk. Many occur as the years following withdrawal of medications was 26% in the medications are being tapered. At least half the recurrences cryptogenic group and 42% in the neurologically abnormal occur within 6 months of medication withdrawal, 60% to group (P 0. One series in severity of mental retardation was an additional prognostic adults reported that 68% of relapses were during drug with- factor within this group. A recent study of the prognosis of epilepsy in rences do occur, they are uncommon (63,73,82). There is no children with cerebral palsy and epilepsy (56) found that the secondary peak in recurrence risk years after discontinuing majority of these children did not achieve remission. The type of cerebral palsy was associated with a differen- who are candidates for medication withdrawal but are main- tial risk of recurrence. Annegers and coworkers (41) found a mean did not find such an association either had very few (74) relapse risk of 1. Certain electroencephalographic patterns are markers higher remission rates in the younger group (41,44,84). Studies that include large num- able prognosis for remaining in remission following drug bers of children with remote symptomatic epilepsy have found withdrawal (25,39,86,90). In one study that examined this question (73), the number of adult studies that have examined this issue 73% of the children with age of onset older than 12 years and is relatively small. However, several other adult studies reported age of onset between 2 and 12 years (P 0. These data recurrence in children with cryptogenic epilepsy, but not in are consistent with the findings of Huttenlocher and cowork- those with remote symptomatic epilepsy. The probability of attain- ing remission and of maintaining remission after medication Epilepsy syndromes are known to be associated with a differen- withdrawal is more a function of the age of onset and the dura- tial prognosis for remission (24,25,91). Syndromes such as tion of the seizure disorder, without a special role for puberty. Results of actual studies in chil- ment and has a high relapse rate when medications are with- dren and adults, however, are conflicting. Interestingly, electroencephalographic abnormality, not just a frankly while specific idiopathic syndromes and the various other gen- epileptiform one, was associated with an increased risk of eralized epilepsy syndromes have different prognoses, the vari- relapse. Unfortunately, there is a paucity of such informa- was associated with a very high risk of recurrence (74). It is clear that future studies will focus on terns, such as irregular generalized spike-and-wave pattern, epilepsy syndrome as a major predictor of long-term prognosis were associated with an increased recurrence risk following and management, both at the time of diagnosis and when in medication withdrawal (42,88). While the recurrence risks in these Other Risk Factors studies are somewhat higher than in studies that used a longer seizure-free interval, they do suggest that, in selected popula- Other risk factors, such as duration of epilepsy, number of tions, a shorter seizure-free interval may be sufficient. Long-term outcomes are not adversely Duration of epilepsy and number of seizures are closely affected by early discontinuation (72). A long duration of epilepsy increases the risk of recurrence, although the magnitude of the effect is small (63,64). Many clinicians have used slow tapering schedules tors will rarely be important (43,47,48). Beyond that, there is much heated debate primarily (barbiturates, phenytoin, carbamazepine, valproate, and etho- based on mythology. The serum drug level does not seem to have a great clinical trial has provided solid data on this issue (75). Available studies show little or no correlation being discontinued after a 2-year or longer seizure-free inter- between drug level prior to discontinuation and seizure recur- val. There were no differences in recurrence risk at 2 years rence and outcome (74), or a very modest effect (59). Seizure type has also not been consistently associated with this well-designed study should finally settle this long-standing recurrence risk, except that children with multiple seizure controversy, although specific drugs, such as barbiturates and types have a poorer prognosis (63,64). Note that specific seizure types may be surrogate rence risk at 2 years, but may delay the recurrence and, thus, markers for epilepsy syndromes with a more favorable or less tends to prolong the period of uncertainty. At this time, it is not clear that any spe- short taper period is particularly important in adolescents and cific seizure type is associated with an increased risk of recur- adults if we advise them to stop driving for 6 months to a year rence following discontinuation of medication. The prognosis for long-term remission appears to be primarily a function of the underlying epilepsy Antiepileptic Drugs syndrome. Five sustained an injury as a result of the initial recurrence, the issue of whether and for how long patients who are including four with lacerations and one with a broken arm. Several retrospective serious injuries in patients with epilepsy discuss patients with studies in adults report that approximately 60% of patients intractable epilepsy who experience injuries such as burns in with medically refractory epilepsy who become seizure-free the context of frequent seizures (106,107). Generally, the risks Furthermore, the risk of status epilepticus in this population is of medication withdrawal in this population appear similar to low and essentially limited to those who have had it before those seen in those with remote symptomatic epilepsy in (13,29). While status epilepticus is frequently reported in remission on medications (51,73). It, therefore, appears rea- patients with epilepsy who are noncompliant (108,109), the sonable to consider medication withdrawal in patients who occurrence of status epilepticus in patients who are withdrawn are seizure-free following resective surgery (95,98,101). The optimal cern that, in addition to the potential for injury, the conse- timing for medication withdrawal in this population is not quences of a seizure include a worse long-term prognosis, and clear. This view is largely based on Gowers state- procedure, why to wait more than a short seizure-free inter- ment that The tendency of the disease is toward self-perpetu- val, such as 6 months or a year, before attempting withdrawal ation; each attack facilitates the occurrence of the next by in this population (98). The potential consequences of the seizure recurrence stigma of seizures is also much more a concern in adolescents include both direct consequences and psychosocial impact. There is no convincing evidence that a brief seizure causes brain damage (34,40,104,105).

Cognitive behavioral therapy and physical exercise for climacteric symptoms in breast cancer patients experiencing treatment-induced menopause: design of a multicenter trial anxiety 6 months buy prozac 10 mg otc. Use of levonorgestrel-releasing intrauterine system in the prevention and treatment of endometrial hyperplasia kindling depression definition buy prozac in india. Hormone replacement therapy after breast cancer: 10 year follow up of the Stockholm randomised trial mood disorder related to general medical condition 20mg prozac with visa. Effect of oral administration of dydrogestrone versus vaginal administration of natural micronized progesterone on the secretory transformation of endometrium and luteal endocrine profile in patients with premature ovarian failure: a proof of concept depression live chat 10mg prozac fast delivery. Standardized multidisciplinary evaluation yields significant previously undiagnosed morbidity in adult women with Turner syndrome depression symptoms questions order prozac 20mg online. Risk of stroke in healthy postmenopausal women during and after hormone therapy: a meta-analysis depression organizations order prozac canada. Sex steroids to maintain cognitive function in women after the menopause: a meta-analyses of treatment trials. Age at natural menopause and all-cause mortality: a 37-year follow-up of 19,731 Norwegian women. Age at natural menopause and total mortality and mortality from ischemic heart disease: the Adventist Health Study. Testosterone concentrations, using different assays, in different types of ovarian insufficiency: a systematic review and meta-analysis. A randomized trial of the effect of testosterone and estrogen on verbal fluency, verbal memory, and spatial ability in healthy postmenopausal women. Estrogen and androgen hormone therapy and well-being in surgically postmenopausal women. Alcohol consumption and breast cancer recurrence and survival among women with early-stage breast cancer: the life after cancer epidemiology study. Wide distribution of the serum dehydroepiandrosterone and sex steroid levels in postmenopausal women: role of the ovary Cardiovascular effects of physiological and standard sex steroid replacement regimens in premature ovarian failure. Factors associated with bone density in young women with karyotypically normal spontaneous premature ovarian failure. Hormonal contraception and risk of venous thromboembolism: national follow-up study. Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database of Systematic Reviews 2004from MacNaughton J, Banah M, McCloud P, Hee J, Burger H. Age related changes in follicle stimulating hormone, luteinizing hormone, oestradiol and immunoreactive inhibin in women of reproductive age. Hormone therapy and cardiovascular disease: a systematic review and meta-analysis. Metabolic effects of oral versus transdermal estrogen in growth hormone-treated girls with turner syndrome. Ambulatory arterial stiffness index in Turner syndrome: the impact of sex hormone replacement therapy. Postmenopausal hormone replacement therapy and cardiovascular disease: the value of transdermal estradiol and micronized progesterone. Menopausal symptoms in young survivors of breast cancer: a growing problem without an ideal solution. Physiological sex steroid replacement in premature ovarian failure: randomized crossover trial of effect on uterine volume, endometrial thickness and blood flow, compared with a standard regimen. Dyspareunia and lubrication in premature ovarian failure using hormonal therapy and vaginal health. A comparison of 25 mg and 50 mg oestradiol implants in the control of climacteric symptoms following hysterectomy and bilateral salpingo-oophorectomy. Comparing the effects of intrauterine progestin system and oral progestin on health-related quality of life and Kupperman index in hormone replacement therapy. Premenopausal ovariectomy-related bone loss: a randomized, double-blind, one-year trial of conjugated estrogen or medroxyprogesterone acetate. Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study. Hormone replacement therapy and the risk of venous thromboembolism: a population-based study. Transition to young adulthood in Ullrich-Turner syndrome: neurodevelopmental changes. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. Association between hormone replacement therapy and subsequent arterial and venous vascular events: a meta- analysis. Are the progestins responsible for breast cancer risk during hormone therapy in the postmenopause Natural vaginal progesterone is associated with minimal psychological side effects: a preliminary study. Simultaneous measurement of serum testosterone and dihydrotestosterone by liquid chromatography-tandem mass spectrometry. Endocrine activity of the postmenopausal ovary: the effects of pituitary down-regulation and oophorectomy. Breast density in women with premature ovarian failure or postmenopausal women using hormone therapy: analytical cross-sectional study. Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe. Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. Comparison of transdermal to oral estradiol administration on hormonal and hepatic parameters in women with premature ovarian failure. Mortality and cancer incidence in persons with numerical sex chromosome abnormalities: a cohort study. Combined estrogen and testosterone use and risk of breast cancer in postmenopausal women. Bleeding profiles and effects on the endometrium for women using a novel combination of transdermal oestradiol and natural progesterone cream as part of a continuous combined hormone replacement regime. The effect of long-term oestradiol implantation on bone mineral density in postmenopausal women who have undergone hysterectomy and bilateral oophorectomy. Oncofertility and preservation of reproductive capacity in children and young adults. A new clinical option for hormone replacement therapy in women with secondary amenorrhea: effects of cyclic administration of progesterone from the sustained-release vaginal gel Crinone (4% and 8%) on endometrial morphologic features and withdrawal bleeding. Comparison of oral estrogens and estrogens plus androgen on bone mineral density, menopausal symptoms, and lipid-lipoprotein profiles in surgical menopause. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Evaluation of high-dose estrogen and high-dose estrogen plus methyltestosterone treatment on cognitive task performance in postmenopausal women. Zuckerman-Levin N, Frolova-Bishara T, Militianu D, Levin M, Aharon-Peretz J, Hochberg Z. Most girls show a progressive ovarian failure and need estrogen treatment for complete breast development and withdrawal bleeding. Lower estrogen doses may stimulate growth, but higher estrogen doses cause acceleration of bone maturation and result in decreased adult height (Ross, et al. It is important to educate the patient that estrogen replacement is usually required until the time of normal menopause to maintain feminization and prevent osteoporosis (Bondy and Turner Syndrome Study Group, 2007). Therefore, the continuum of care through childhood and adolescence into adulthood is mandatory. Because estrogens accelerate bone maturation, estrogen replacement has traditionally been delayed, often until 15 or 16 years of age, to allow additional time for linear growth with growth hormone therapy (Chernausek, et al. This approach can be considered for other causes of delayed or absent puberty when the condition is known from an early age. Multiple forms of estrogen are available; oral estrogens have been the most widely used. Similarly, the oral contraceptive pill is best avoided, because the synthetic estrogen doses are too high and the typical synthetic progestin may interfere with optimal breast and uterine development (Bondy and Turner Syndrome Study Group, 2007). Furthermore, the oral contraceptive pill is conventionally taken with a pill-free week, resulting in 3 months of estrogen deficiency for each year of use. Oral ethinylestradiol and micronized estradiol have both been used for puberty induction. As oral ethinylestradiol is a synthetic estrogen that is not metabolized by the liver, it can be delivered at relatively low doses. Natural estrogens are metabolised in the liver and must be given either orally in higher doses (Leung, et al. Natural estrogens have less pronounced effects on coagulation factors, lipid profiles and blood pressure than synthetic estrogens (Lobo, 1987). Puberty is a relatively slow process and the replacement therapy in the induction process should mimic this (Hindmarsh, 2009). Although the appropriate starting dose has yet to be determined, estrogen replacement is usually begun at one-tenth to one-eighth of the adult replacement dose and then increased gradually over a period of 2 to 4 years (Divasta and Gordon, 2010). To allow for normal breast and uterine development, it seems advisable to delay the addition of progestin at least 2 years after starting estrogen or until breakthrough bleeding occurs (Bondy and Turner Syndrome Study Group, 2007; Fritz and Speroff, 2010). Based on these principles, suggested age-specific preparations and doses of estrogen substitution therapy in adolescence are listed in table 13. This table is only a guide and individual tailoring of dose and timing will be required. In cases of later diagnosis of pubertal failure and for those girls in whom growth is not a consideration, estrogens may be started at somewhat higher doses and escalated more rapidly (Davenport, 2008). The starting dose of E2 should be increased at 3-6 months interval over 2 years to adult dose. The starting dose and dose escalations are not evidence-based and should be individualised with monitoring of breast development since too rapid breast development may cause stretch marks and asymmetry. Uterine growth was significantly greater in the transdermal E2 group (Nabhan, et al. Four studies reported inconclusive results for uterine size after oral estrogen therapy. Three girls being followed longitudinally showed normal uterine growth and maturation to the adult configuration (Illig, et al. Metabolic actions Metabolic actions of oral versus transdermal estrogen in adolescents have been examined in 4 short-term randomized trials. No long-term studies were found comparing the effect of oral versus transdermal estrogen on bone health during adolescence. However, systemic administration of increasing doses estradiol, preferably by transdermal application, is the only form of therapy to achieve natural levels of estradiol in blood and mimic normal estradiol physiology in adolescence and adulthood (Ankarberg-Lindgren, et al. For regular withdrawal bleeding and normal breast and uterine development progestogen should be added at least 2 years after starting estrogen or when breakthrough bleeding occurs (Bondy and Turner Syndrome Study Group, 2007; Fritz and Speroff, 2010). In cases of later diagnosis of pubertal failure and for those girls in whom growth is not a consideration, estrogens may be started at somewhat higher doses and escalated more rapidly (Davenport, 2010). With increasing doses of oral and transdermal 17-estradiol normal breast and pubic hair development can be achieved (Cisternino, et al. With higher starting doses of E2 and/or more rapid dose escalation, breast development should be monitored for stretch marks and asymmetry. The extent of uterine development achievable with oral estrogens is uncertain (Paterson, et al. Short-term comparison of oral and transdermal estrogen showed a significant greater uterine growth with transdermal E2 (Nabhan, et al. No long-term studies compared the effect of oral versus transdermal estrogen on uterine growth and development, or more importantly obstetric outcomes. There is either no effect or comparable effects of oral or transdermal estrogen on body composition and several metabolic parameters in adolescents (Mauras, et al. The short-term effect of oral or transdermal 17-estradiol on bone accrual was comparable (Torres-Santiago, et al. Recommendations Puberty should be induced or progressed with 17-estradiol, starting with C low dose at the age of 12 with a gradual increase over 2 to 3 years. In cases of late diagnosis and for those girls in whom growth is not a D concern, a modified regimen of estradiol can be considered. Transdermal estradiol results in more physiological estrogen B levels and is therefore preferred. Nocturnal application of transdermal estradiol patches produces levels of estradiol that mimic those seen at the onset of spontaneous puberty in girls. Puberty induction in Turner syndrome: results of oestrogen treatment on development of secondary sexual characteristics, uterine dimensions and serum hormone levels. Growth hormone therapy of Turner syndrome: the impact of age of estrogen replacement on final height. Cisternino M, Nahoul K, Bozzola M, Grignani G, Perani G, Sampaolo P, Roger M, Severi F. Transdermal estradiol substitution therapy for the induction of puberty in female hypogonadism.