Martha S. Nolte Kennedy MD

  • Clinical Professor, Department of Medicine
  • University of California, San Francisco

https://profiles.ucsf.edu/martha.noltekennedy

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In girls anxiety symptoms tight chest order cymbalta 20 mg visa, primary epispadias is characterized by a divided (bifid) clitoris, wide urethra, and bladder neck deficiency. Although some visible abnormality is invariably present from birth it may, nevertheless, remain undetected in girls until they are investigated for incontinence in later childhood. Likewise, distal epispadias in boys may be concealed by an intact foreskin and may not become apparent until the foreskin becomes retractile-or at the time of circumcision. In severe cases, cystoscopy reveals marked deficiency of the bladder neck muscle with the veru montanum located within the bladder and abnormal appearances of the trigone. However, the cystoscopic findings do not reliably predict the eventual prognosis for continence. Surgical repair In boys who are continent, the Cantwell-Ransley epispadias repair7 yields good results-although the penis may still appear relatively short. When epispadias is associated with incontinence, the Kelly operation is now the preferred option. Despite optimal reconstruction, however, it may be difficult to create continence and normal spontaneous voiding because of the dysplastic nature of the bladder neck and sphincter musculature. It is usually evident from birth as a fluid discharge (of urine) from the umbilicus. Rarely, a persistent blind-ending section of patent urachus which communicates with the bladder lumen can create a non-obstructive diverticulum, which is visualized as an incidental finding on a micturating cryptogram. In girls, the Kelly operation has a high success rate-both in terms of continence and correction of the bifid clitoris. The alternative approach consists of bladder neck reconstruction, cystoplasty, and a Mitrofanoff procedure. Urachal anomalies In early gestation the urinary tract communicates freely with the amniotic cavity via the urachus, which extends from the bladder to the umbilicus. The lumen of the urachus normally closes around the twelfth week leaving a non-patent fibrous cord-the median umbilical ligament. The commonest urachal anomaly (accounting for approximately 50% of cases) is a sinus in which a patent section of the residual urachus communicates with the umbilicus-but not with the bladder. Presentation is with umbilical discharge, persistent granulation tissue or pain, and localized tenderness. Investigation consists of ultrasound8 and contrast sinography (to determine the proximal extent of the sinus). Urachal cysts account for approximately one-third of cases and usually present with infection, the commonest organism being Staphylococcus aureus. Asymptomatic urachal cysts are sometimes identified incidentally during ultrasound imaging for unrelated indications.

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Penetrance lnaeases with each successive generation owing to the progressive expansion of a triplet repeat element (see text anxiety symptoms tinnitus buy cymbalta 60 mg mastercard. Expansion Is dependent on maternal Inheritance of the abnormal allele; thus, daughters of normal ttansmlttlng males (Indicated with aT In 11-4 are nonpenetrant. X-assoclated mental retardation syndrome triplet repeat the heavy anows show expansion of the triplet repeat, which Is thought to occur posteygotlcally after the premutatlon or full mutation Is transmitted through the female germllne. Daughters with the full mutation may not express the fragile X-assoclated mental retardation phenotype, depending on the proportion of cells In which the mutant allele happens to lie on the Inactive X chromosome. Affected females generally have either milder intellectual disability (when compared to affected males) or only subtle impairments of visuospatial ability, and the condition may not be evident or diagnosed until it is suspected after identification of an affected male relative. Vutually all affected males are born to females who are either affected or carry the premutatio:n, and the. The inheritance of fragile X-assodated mental retardation syndrome exhibits several unusual features and is often described in tenn. In particular, the likelihood that an individual carrying an abnormal chromosome will manifest clinical features depends on the nwnber ofgenerations through which the abnormal chromosome has been b:ansmitted and the sex of the transmitting parent. This is refle<:ted in low risk figures for brothers and sisters of transmitting males: 9% and 596, respectively, compared with 40% and 16% for their maternal grandsons and granddaughters. This latter observation, in which the penetrance or expressivity (or both) of a genetic disease seems to increase in successive generations, is sometimes referred to more generally as genetic anticlpation. Genetic anticipation in fragile X-associated mental retardation syndrome is caused by progressive expansion ofthe triplet repeat A similar phenomenon occurs in several neurodegenerative disorders such as Huntington disease and spinocerebellar ataxia (ie, grandchildren are affected more severely than grandparents). The neurodegenerative disorders are caused by production of abnonnal proteins; fragile X-associated mental retardation is caused by failure to produce a normal protein. Although the biochemical mechanisms are different, the underlying molecular causes of genetic anticipation are identical and involve progressive expansion of an unstable triplet repeat In addition to triplet repeat expansion, genetic anticipation can be caused by bias of ascertainment, which occurs when a mild or variably expressed condition first diagnosed in grandc. In contrast to genetic anticipation caused by expansion of a triplet repeat, anticipation caused by bias of ascertainment affects the apparent, rather than the actual, penetrance. In transmitting males and in unaffected carrier females, the number of repeats is usually between 70 and 100. Remarkably, alleles with fewer than 50 repeats are very stable and almost always transmitted without a change in repeat number. However, alleles with 55 or more repeats are unstable and often exhibit expansion after maternal transmission; these individuals are said to carry a premutation. In both cases, the mechanism is likely to be explained by somatic expansion of the premutation (see later discussion). The degree of expansion is related to the number of repeats; premutation alleles with a repeat number less than 60 rarely are amplified to a full mutation, but premutation alleles with a repeat number greater than 90 are usually amplified to a full mutation. The number of repeats in the full mutation-observed both in affected males and in affected females-is always greater than 200 but is generally heterogeneous, suggesting that once this threshold is reached, additional amplification occurs frequently in somatic cells.

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Risk of cancer incidence before the age of 15 years after exposure to ionising radiation from computed tomography: results from a German cohort study 0503 anxiety and mood disorders quiz cheap 20 mg cymbalta with visa. Radiation risks from medical X-ray examinations as a function of age and sex of the patient. Estimation of Effective Dose in Diagnostic Radiology from Entrance Surface Dose and Dose-Area Product Measurements, 1994. Freeman Ultrasound physics Greyscale ultrasound Ultrasound creates an image using short duration pulses of high frequency sound waves generated by electrically stimulating a piezoelectric crystal in a hand-held ultrasound transducer. The pressure wave generated is transmitted to the patient using a coupling gel between the transducer and skin surface. Returning echoes hit the same crystal and the vibrations induced are reconverted to an electrical signal which is then processed to create the image. If the interface is close to perpendicular with the ultrasound beam (more than 60 degrees) the reflected echo will return to the transducer and be detected; its strength determines the brightness of the interface on the display. At soft tissue/air or soft tissue/bone interfaces the difference in acoustic impedance is so great that almost all the sound is reflected and none left to image deeper structures; the inability of ultrasound to penetrate gas-filled organs (such as bowel or lung) and bone can cause difficulty in obtaining a diagnostic ultrasound study. Other echoes are derived from tiny tissue structures that are similar in size to the ultrasound wavelength; rather than reflect the ultrasound beam these cause it to be scattered in all directions. This phenomenon is of particular importance in generating a Doppler signal from moving red blood cells. Ultrasound is assumed to have a constant velocity in soft tissue (about 1,540 m/ s); therefore the time interval between transmission of the ultrasound pulse and reception of the returning echo can be used to calculate the distance of the reflecting interface from the transducer. The crystals within the transducer are fired sequentially and the returning reflected and backscattered echoes analysed for their strength and delay. This information is used to construct a real-time two-dimensional image, referred to as the greyscale or B (brightness)-mode. Higher frequency sound produces images of higher resolution, but the sound is attenuated more quickly and so tissue penetration is reduced. Selecting the appropriate transducer is therefore a trade-off between image quality and depth penetration. Resolution is optimized by ensuring that the focus of the beam is adjusted to the level of the region of interest. Harmonic imaging and spatial compounding are techniques that are now routinely employed by most manufacturers to produce images with less artefact and greater resolution or clarity. Doppler ultrasound the Doppler effect is the change in frequency that occurs when a sound source or detector are moving relative to one another.

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Intra-arterial infusion of 5-fluorouracil for recurrent adenocarcinoma of bladder anxiety 9 year old buy 60mg cymbalta visa. Prospective trial of ifosfamide, paclitaxel, and cisplatin in patients with advanced non-transitional cell carcinoma of the urothelial tract. Surgical and chemotherapeutic options for urachal carcinoma: report of ten cases and literature review. Secondary neoplasms of the bladder are histological mimics of nontransitional cell primary tumours: clinicopathological and histological features of 282 cases. Value of a panel of antibodies to identify the primary origin of adenocarcinomas presenting as bladder carcinoma. Immunohistochemical distinction between primary adenocarcinoma of the bladder and secondary colorectal adenocarcinoma. Deletedin-colon-cancer protein expression in patients with adenocarcinoma of the urinary tract and a history of colorectal cancer. Standing the test of time: long-term outcome of reconstruction of the exstrophy bladder. Secondary malignancies in different forms of urinary diversion using isolated gut. Transitional cell carcinoma of the bladder following augmentation cystoplasty for the neuropathic bladder. Glandular lesions of the urinary bladder:clinical significance and differential diagnosis. Robotic assisted laparoscopic partial cystectomy and urachal resection for urachal adenocarcinoma. Advanced carcinoma of bladder: treatment using hypogastric artery infusion with 5-fluorouracil, either as a single agent or in combination with 54. It is estimated that about 7,200 new cases of tumour of the renal pelvis or ureter occur each year in the European Union. However, since first described in the 1950s the difference of incidence has decreased dramatically. More recently, Chinese herb nephropathy has been described in patients exposed to a Chinese herbal product containing Aristolochia fangchi. Aristolochia fangchi, as well as Aristolochia clematis (a plant endemic to the Balkans) contains aristolochic acid, which is described as a carcinogen responsible of a genetic mutation. The role of arsenic in the carcinogenesis is probably not sufficient to explain the higher incidence on this Asian island. Phenacetin was widely used as an analgesic for 40 years but has been abandoned since the 1980s when its role as a carcinogen for the upper urinary tract was demonstrated. Age Most recent series report an average age of occurrence of 70 years; with incidence increasing with age.

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The luminal subgroup was associated with a more inflamed environment than the basal subtype anxiety 30002 cheap cymbalta 30mg with mastercard. The luminal subtype was also found to have high Teffector cells and low stromal gene expression. Further work on the biology of immune response to checkpoint inhibits is clearly a priority. Atezolizumab showed encouraging durable response rates, survival, and tolerability, supporting its therapeutic use in untreated metastatic urothelial cancer. The adverse event profile for pembrolizumab was consistent with previous experience with other similar agents. Preliminary analysis of the first 100 patients enrolled in the trial were presented. Thirty patients had this level of expression, of whom 11 (37%) responded to treatment. The median duration of response had not yet been reached and treatment was well tolerated. Pembrolizumab has substantial activity with a favourable safety profile as first-line therapy in cisplatin-ineligible patients with metastatic bladder cancer. The biomarker cut point requires validation in the full study population, but appears to identify patients most likely to respond to pembrolizumab. Immunotherapy is rapidly redefining our treatment approach for patients that are ineligible for cisplatin-based chemotherapy. Other agents such as durvalumab and tremelimumab are being evaluated in bladder cancer. The trial has three arms: chemotherapy versus single-agent durvalumab, versus a combination of durvalumab and tremelimumab. A better understanding of the molecular biology of bladder cancer will undoubtedly influence the selection of new therapeutic modalities. Several signalling pathways are activated in bladder urothelial carcinoma, but no targeted therapy, either alone or in combination with conventional cytotoxic chemotherapy, has been shown to significantly improve treatment outcomes. Whether or not this approach to therapy will lead to better results must still be determined. The future of metastatic urothelial carcinoma treatment lies in the ability to deliver personalized therapy. This area remains an active research field today and participation in clinical trial needs to be prioritized. Comparative effectiveness of cisplatinbased and carboplatin-based chemotherapy for treatment of advanced urothelial carcinoma.

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Physical examination should include abdominal palpation combined with palpation and visual examination of the lower spine to look for possible stigmata of occult spinal dysraphism anxiety symptoms light sensitivity order cymbalta 60 mg with visa. Its use is therefore largely limited to follow up rather than initial investigation. From their experience, Lytzen and associates11 concluded that use of the guidelines was not appropriate for children experiencing their first episode of pyelonephritis. Where possible, this investigation should be deferred for four to six months in order to distinguish between acute, reversible changes and established renal scarring. A practical approach to investigation this is largely determined by the age of the child and the severity and nature of the urinary tract infection. Mechanismms of uropathogenic Escherichia coli persistence and eradication from the urinary tract. Circumcision for the prevention of urinary tract infection in boys: A systematic review of clinical trials and observation studies. Short compared with standard duration of antibiotic treatment for urinary tract infection: a systematic review of randomised controlled trials. Risk assessment of renal cortical scarring with urinary tract infection by clinical features and ultrasonography. Renal sonography is not a reliable screening examination for vesicoureteral reflux. Impact of a more restrictive approach to urinary tract imaging after febrile urinary tract infection. Conclusion the greater risk of renal damage in infants and young children coupled with the higher yield of abnormal findings in this age group justifies a more intensive approach to investigation. Any benefit in identifying the small percentage with underlying urological abnormalities must be balanced by the importance of minimizing the burden of unnecessary, invasive investigations in healthy children. Thomas Aetiology the anatomy of the normal ureterovesical junction creates a valve mechanism preventing the retrograde flow of urine at physiological bladder pressures. Reflux-related renal damage (reflux nephropathy) Experimental studies have demonstrated the importance of intrarenal reflux in promoting the transmission of organisms from the collecting system into the renal parenchyma. Abnormal papillae are located mainly in the upper and lower poles of the kidney, which are the areas at greatest risk of developing focal pyelonephritic scarring. Although renal dysplasia can be diagnosed with some confidence on imaging in the newborn period it can prove difficult, if not impossible to accurately differentiate between infective and congenital mechanisms of renal damage once a kidney has been exposed to severe or recurrent pyelonephritis. The risk of infective renal scarring is greatest in infancy and experimental evidence suggests that this risk is maximal after first major episode of pyelonephritis. This is particularly important in males in view of the possible presence of outflow obstruction.

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Auscultation of the rub is best heard using the diaphragm of the stethoscope with the patient leaning forward while exhaling (which brings the pericardium closer to the chest wall and stethoscope) anxiety symptoms depersonalization buy discount cymbalta 20 mg. In its full form, the rub consists of three components, corresponding to the phases of greatest cardiac movement: ventricular contraction, ventricular relaxation, and atrial contraction. Diagnostic Studies the presence of pleuritic, positional chest pain and the characteristic pericardia! However, certain laboratory studies are helpful to confirm the diagnosis and to assess for impending complications. Blood studies typically reveal signs of acute inflammation, including an increased white blood cell count (usually a mild lymphocytosis in acute viral/idiopathic pericarditis) and Diseases of the Pericardium 339::v:, ~~ ~ ~ t~. Some patients with acute pericarditis also demonstrate elevated serum cardiac biomarkers. Additional studies that may be useful in individual cases to define the cause of pericarditis include (1 purified protein derivative skin test for tuberculosis, (2) serologic tests (antinuclear antibodies and rheumatoid factor to screen for connective tissue diseases, and (3) a careful search for malignancy, especially of the lung and breast (physical examination supplemented by chest radiography and mammography. Treatment Idiopathic or viral pericarditis is a self-limited disease that usually runs its course in 1 to 3 weeks. Management consists of rest, to reduce the interaction of the inflamed pericardia! Colchicine, a drug with anti-inflammatory properties usually used to treat gout, may be useful as an additional agent in acute pericarditis. The forms of pericarditis related to Ml are treated in a similar fashion, with rest and aspirin. Other nonsteroidal anti-inflammatory agents are often avoided immediately following an Ml because of experimental evidence linking them to delayed healing of the infarct. Purulent pericarditis requires more aggressive treatment, including catheter drainage of the pericardium and intensive antibiotic therapy. Pericarditis in the setting of uremia often resolves following intensive dialysis. A larger volume of fluid may accumulate in association with any of the forms of acute pericarditis previously described. In addition, noninflammatory serous effusions may result from conditions of (I increased capillary permeability e. Chylous effusions may occur in the presence of lymphatic obstruction of pericardia! Notice that the initial portion of the curve is nearly flat, indicating that at the low volumes normally present within the pericardium, a small increase in volume leads to only a small rise in pressure. At that point, even a minor increase in volume can translate into an enormous compressive force on the heart. Schematfc representation of the wlume-pressure relattonshfp of normal perlcan:llum.

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The length and quality of the murmur are dictated by the systolic pressure gradient between the left ventricle and the relatively noncompliant left atrium anxiety natural supplements generic cymbalta 60 mg otc. For example, intravenous nitroprusside is a potent vasodilator that decreases arterial resistance, thereby augmenting forward flow and diminishing the regurgitant volume. In this way, cardiac output and pulmonary congestion may improve at least transiently. Surgical intervention consists of either mitral valve repair (reconstruction of the native valve as described below) or replacement, depending on the underlying cause and valve anatomy. Mitral valve repair is the preferred operative technique when feasible, and involves the reconstruction of parts of the valve responsible for the regurgitation. For example, a perforated leaflet may be patched with transplanted autologous pericardium, or ruptured chordae may be reattached to a papillary muscle. Mitral repair preserves native valve tissue, and eliminates many of the problems associated with artificial valves described later in the chapter. These rates are higher if concurrent coronary artery bypass grafting is performed. In general, mitral valve repair is more often appropriate for younger patients with myxomatous involvement of the mitral valve, and mitral replacement is more often undertaken in older patients with more extensive valve pathology. In this procedure, a catheter is advanced percutaneously from the femoral vein into the right side of the heart, then into the left atrium via a puncture through the interatrial septum (similar to mitral balloon valvuloplasty), and advanced into the left ventricle. A mechanical clip is then deployed, which grasps and tethers the anterior and posterior mitral leaflets together at one location and is left in place, reducing the size of the regurgitant orifice. Other names for this condition include floppy mitral valve, myxomatous mitral valve, and Barlow syndrome. Pathologically, the valve leaflets, particularly the posterior leaflet, are enlarged, and the normal dense collagen and elastin matrix of the valvular fibrosa is fragmented and replaced with loose myxomatous connective tissue. Additionally, in more severe lesions, elongated or ruptured chordae, annular enlargement, or thickened leaflets may be present. Occasionally, rupture of myxomatous chordae in this condition can cause sudden, severe regurgitation and pulmonary edema. Other potential complications include infective endocarditis, peripheral emboli owing to microthrombus formation on the redundant valve tissue, and atrial or ventricular arrhythmias. Degenerative disease of a trileaflet valve shares many pathologic features in common with atherosclerosis, as described below. Over time, valvular myofibroblasts differentiate into osteoblasts and deposit calcium hydroxyapatite crystals, resulting in leaflet thickening and stiffening.

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Marus, 28 years: Clinical Features Cardiac tamponade should be suspected in any patient with known pericarditis, pericardia! For example, reproductive decision malting in families at risk for osteogenesis imperfecta is influenced greatly by the relative likelihood of producing a child who will never walk and will require multiple orthopedic operations versus a child whose major problems will be a few long bone fractures and an increased risk of mixed sensorineural and conductive hearing loss in childhood and adulthood. It is here that the relationship between the patient and health care provider, and the role of medical professionals as community leaders advocating healthy lifestyles, remain of cardinal importance.

Aldo, 25 years: Follow-up guidelines after radical or partial nephrectomy for localized and locally advanced renal cell carcinoma. Penile preserving surgery and surgical strategies to maximize penile form and function in penile cancer: recommendations from the United Kingdom experience. Other means of reducing preload include administration of nitrates (often intravenously).

Aila, 29 years: However, pathologic changes in pericardial stiffness, or the accumulation of fluid within the pericardia! Because methylxanthines (caffeine, theophylline) competitively antagonize the adenosine receptor, higher doses of adenosine may be necessary in patients using those substances. Air-filled tissues, such as the lung, absorb few x-rays and expose the underlying film (or electronic recording sensor), causing it to appear black.

Berek, 65 years: For example, a prominent a wave is seen in tricuspid stenosis and right ventricular hypertrophy. Intravesical chemotherapy prophylaxis in primary superficial bladder cancer: a meta-analysis of 3703 patients from 11 randomized trials. The location and degree of abnormal systolic contraction and decreased systolic wall thickening indicate the extent of an infarction and implicate the responsible coronary artery.

Tamkosch, 43 years: Videourodynamics is an invasive investigation and the insertion of urinary and rectal catheters can cause considerable distress in children. Antihypertensive effectiveness is no greater than that of other drugs that inhibit the reninangiotensin-aldosterone axis and long-term effects on cardiovascular event rates are not yet known. The sarcomere is composed of alternating thin (actin) and thick (myosin) myofilaments.

Wilson, 21 years: They are used when maintenance of serum potassium levels is crucial and in states characterized by aldosterone excess. Human chorionic gonadotrophin treatment prior to microdissection testicular sperm extraction in non-obstructive azoospermia. The renal pelvis sometimes appears to be outside of the confines of the kidneys, where it often has a distended appearance (the extrarenal pelvis).

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References

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  • Travis W BE, Muller-Hermlink H, Harris C, eds. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. Lyon: IARC, 2004.
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  • Lancet JE, Uy GL, Cortes JE, et al. Final results of a phase III randomized trial of cpx-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol 2016;34(suppl):7000.