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Deputy Director, University of Kansas School of Medicine

If better management is sought, the development, assessment and diffusion of applicable technologies that increase the production of food per unit of water, without Wetlands 95 Box 7. The methodologies are integrated and incorporate biodiversity, economics and livelihoods approaches. The toolkit was put into practice in two demonstration sites: the Stung Treng Ramsar site in Cambodia and Mtanza-Msona village in Tanzania (Allen and Springate-Baginski, 2008). Following initial preparation and orientation activities, notably clarifying the management objectives of stakeholders, the integrated wetland assessment fieldwork was completed, and integrated reports on the livelihood, biodiversity and economic values of the areas were prepared. Information obtained in the Stung Treng Ramsar site was included in the management and zoning plan for this site, towards supporting pro-poor wetland conservation and sustainable use to the benefit of local livelihoods and biodiversity. Data obtained from the second demonstration site helped local communities to understand the importance of wetland resources in their livelihoods. The main output of the project was An Integrated Wetland Assessment Toolkit: A Guide to Good Practice (Springate-Baginski et al. This guide provides a set of integrated assessment methods that combine and investigate the links between biodiversity, economics and livelihoods, with a particular focus on strengthening pro-poor approaches to wetland management. It aims to assist in overcoming the current methodological and information gaps in wetland planning, to factor wetland values into conservation and development decision making and management planning, and to assist in identifying areas of potential conflicting priorities. The toolkit is expected to be of use to wetland site managers, conservation and development planners, and researchers from both natural and social science disciplines. The studies in Cambodia and Tanzania brought experts from social, ecological and economic backgrounds to work together. It was not easy to convince them of the value of the work in each of the other two disciplines. For example, it was challenging, but ultimately successful, to convince the social scientists of the value of biodiversity assessment; vice versa, it was challenging to find good models and tools as examples of integrated work (Allen and Springate-Baginski, 2008). Though such technologies have already been identified and are available, the majority of countries have failed to promote them and to penalize more damaging practices, and less developed countries lack the financial resources to improve their capacity to adopt such approaches (Millennium Ecosystem Assessment, 2005). However, certain strategies can be adopted in order to realign policies on agriculture and wetlands (Peden et al. Adopt supporting strategies that maintain and improve wetland ecosystem services so that a broader range of stakeholders, including the rural poor, receive the benefits. Assess water use by the surrounding agroecosystems and adapt its use to be in harmony with a sustainable supply, using trade-off analyses. Improve land and water management techniques after a comprehensive evaluation of the social and ecological products and services supported by the wetlands for women and men. Provide alternate livestock drinking sites away from sensitive wetland areas, not only for the benefit of the wetlands, but also as a means to reduce animal health risks. The wetland farmers, 90% of whom are women, are among the poorest of the country and depend on these freshwater ecosystems as their only source of food. However, their farming practices, passed from generation to generation, are causing increased erosion, increased desiccation, poor soil fertility and low productivity. The project aims to promote awareness of the value of goods and services of the Sand River wetlands in providing livelihood security to poor rural communities, and to develop good agricultural practices among wetland farmers and harvesters in the Sand River Basin. The project started by evaluating the nature and intensity of farming practices in the wetlands; detailed and rapid appraisals on 60 plots were completed using interviews, field assessments and documentary photographs. The appraisals confirmed erosion, desiccation and poor soil fertility as the main negative outcomes from farming practices. Because wetland farmers relied very much on the wetlands for their livelihoods, it was assumed that they understood their value, but this was shown not to be true, and getting farmers to change their practices and think about long-term management of the wetlands was a challenge. Based on this information, all 60 farmers were grouped according to shared issues, and were engaged in a series of workshops and field visits, whereby they were introduced to basic wetland concepts, conservation tillage methods and good wetland practices.

Hematuria is often the first symptom, but it often occurs late, after invasion of the renal vein or widespread metastases, frequently to lung, bone, or brain. At about the eighth week of development a cloacal membrane forms within the cloaca and separates the cloaca into a dorsal rectum and a ventral urogenital sinus. Initially the urinary bladder is continuous with the allantois, which constricts and forms the thick, fibrous urachus. The urachus in turn becomes attenuated, but still remains attached to the bladder dome and forms the median umbilical ligament in the adult. Incom- Urinary System Answers 381 plete attenuation of the urachus (persistent urachus) can lead to formation of a urachal cyst, urachal sinus, or urachal fistula. The end attached to the bladder can remain and form a bladder diverticulum, while the central portion can remain and form a urachal cyst. Urachal sinuses and fistulas still connect the umbilicus to the urinary bladder, and therefore urine can leak at the site of the umbilicus. Normally, mesodermal tissue grows onto the cloacal membrane to form the muscles of the lower abdominal wall. This leads to persistence of the cloacal membrane, which can become quite thin and rupture. This in turn causes the posterior bladder mucosa to evert through this defect in the anterior abdominal wall. This condition is called exstrophy and is associated with recurrent urinary infections and epispadias in males. There is also an increased incidence of neoplastic transformation, most commonly adenocarcinoma. An omphalocele refers to protrusion of the intestines through an unclosed umbilical ring. This abnormality results from incomplete internalization of the intestines during fetal growth. Instead, viscera herniate through a defect in the anterior abdominal wall just lateral to the umbilicus. The organism may take up residence in the prostate, producing chronic and active prostatitis. Prostatic hypertrophy, epididymitis, orchitis, and renal stones may cause urinary symptoms but also produce other signs and symptoms that distinguish them from nonspecific urethritis. Acute cystitis histologically reveals stromal edema and an infiltrate of neutrophils. In most cases cystitis is secondary to infections of the bladder, usually by coliform bacteria. Cystitis occurs more commonly in females and is associated with sexual intercourse, pregnancy, and instrumentation. Hemorrhage may also be present (hemorrhagic cystitis) and is usually the result of radiation injury, chemotherapy, or an adenovirus infection. In particular, there is disagreement as to whether papillary lesions may be benign (papillomas). Pathologists do agree, however, on the existence of a rare type of benign lesion called an inverted papilloma, which is characterized by nodular mucosal lesions that histologically have an endophytic growth pattern. Malignant neoplasms of the bladder may be transitional cell carcinomas, which are by far the most common type of tumor of the urinary bladder; squamous cell carcinomas, which produce keratin; or adenocarcinomas, which form glandular structures. In contrast, squamous cell carcinomas of the urinary bladder are quite rare except in Egypt and other areas of the Middle East, where they are associated with schistosomiasis. Similarly, adenocarcinomas of the urinary bladder are quite rare, except that they may be associated with urachal epithelial remnants located in the dome of the bladder, glandular metaplasia, or cystitis glandularis. Urethral opening on the dorsal surface of the penis due to faulty positioning of the genital tubercle c. Urethral opening on the superior surface of the penis due to failure of downgrowth of mesoderm over the anterior bladder. Urethral opening on the ventral surface of the penis due to failure of the urethral folds to close 355. An uncircumcised 49-year-old male presents with the sudden onset of severe pain in the distal portion of his penis.

A constellation of premenstrual moliminal symptoms such as bloating, breast tenderness, and food cravings often occur several days before menses in ovulatory cycles, but their absence cannot be used as evidence of anovulation. Methods that can be used to determine whether ovulation is likely include a serum progesterone level >5 ng/mL 7 days before expected menses, an increase in basal body temperature of >0. Ultrasound can be used to detect the growth of the fluid-filled antrum of the developing follicle and to assess endometrial proliferation in response to increasing estradiol levels in the follicular phase, as well as the characteristic echogenicity of the secretory endometrium of the luteal phase. The triggers for adrenarche remain unknown but may involve increase in body mass index as well as in utero and neonatal factors. Menarche is also preceded by breast development (thelarche), which is exquisitely sensitive to the very low levels of estrogens that result from peripheral conversion of adrenal androgens and the low levels of estrogen secreted from the ovary early in pubertal maturation. Breast development precedes the appearance of pubic and axillary hair in 60% of girls. There has been a gradual decline in the age of menarche over the past century, attributed in large part to improvement in nutrition, and there is a relationship between adiposity and earlier sexual maturation in girls. Both adrenarche and breast development occur 1 year earlier in African-American compared with Caucasian girls, although the timing of menarche differs by only 6 months between these ethnic groups. The growth spurt is generally less pronounced in girls than in boys, with a peak growth velocity of 7 cm/year. Linear growth is ultimately limited by closure of epiphyses in the long bones as a result of prolonged exposure to estrogen. However, there are differences in the timing of normal puberty and differences in the relative frequency of specific disorders in girls compared with boys. Precocious Puberty Traditionally, precocious puberty has been defined as the development of secondary sexual characteristics before the age of 8 in girls based on data from Marshall and Tanner in British girls studied in the 1960s. More recent studies led to recommendations that girls be evaluated for precocious puberty if breast development or pubic hair were present at <7 years of age for Caucasian girls or <6 years for African-American girls. Precocious puberty is most often centrally mediated (Table 10-2), resulting from early activation of the hypothalamic-pituitary-ovarian axis. In girls, centrally mediated precocious puberty is idiopathic in 85% of cases; however, neurogenic causes must also be considered. Management of peripheral precocious puberty involves treating the underlying disorder (Table 10-2) and limiting the effects of gonadal steroids using aromatase inhibitors, inhibitors of steroidogenesis, and estrogen receptor blockers. It is important to be aware that central precocious puberty can also develop in girls whose precocity was initially peripherally mediated, as in McCune-Albright syndrome and congenital adrenal hyperplasia. For example, premature breast development may occur in girls before the age of 2 years, with no further progression and without significant advancement in bone age, androgen production, or compromised height. Premature adrenarche can also occur in the absence of progressive pubertal development, but it must be distinguished from late-onset congenital adrenal hyperplasia and androgen-secreting tumors, in which case it may be termed heterosexual precocity. The diagnostic considerations are very similar to those for primary amenorrhea (Chap. Between 25 and 40% of delayed puberty in girls is of ovarian origin, with Turner syndrome constituting a majority of such patients. Functional hypogonadotropic hypogonadism encompasses diverse etiologies such as systemic illnesses, including celiac disease and chronic renal disease, and endocrinopathies, such as diabetes and hypothyroidism. In addition, girls appear to be particularly susceptible to the adverse effects of abnormalities in energy balance that result from exercise, dieting, and/or eating disorders. Together, these reversible conditions account for 25% of delayed puberty in girls. Congenital hypogonadotropic hypogonadism in girls or boys can be caused by mutations in several different genes or combinations of genes (Chap. Family studies suggest that genes identified in association with absent puberty may cause delayed puberty and that there may be a genetic susceptibility to environmental stresses such as diet and exercise. Although neuroanatomic causes of delayed puberty are considerably less common in girls than in boys, it is always important to rule these out in the setting of hypogonadotropic hypogonadism. In a study of 5574 English and American women who ultimately conceived, pregnancy occurred in 50% within 3 months, 72% within 6 months, and 85% within 12 months. The infertility rate has remained relatively stable over the past 30 years, although the proportion of couples without children has risen, reflecting a trend to delay childbearing.

Recent findings concerning the genetic basis of parathyroid carcinoma (distinct from that of benign adenomas) indicate the need, in these kindreds, for family screening. The former, by definition, can lead to uncontrolled cellular growth and function by activation (gain-of-function mutation) of a single allele of the responsible gene, whereas the latter requires loss of function of both allelic copies. Biallelic loss of function of a tumor-suppressor gene is usually characterized by a germ-line defect (all cells) and an additional somatic deletion/mutation in the excised tumor. Inheritance of one mutated allele in this hereditary syndrome, followed by loss of the other allele via somatic cell mutation, leads to monoclonal expansion and tumor development. Consistent with the Knudson hypothesis for two-step neoplasia in certain inherited cancer syndromes, the earlier onset of hyperparathyroidism in the hereditary syndromes reflects the need for only one mutational event to trigger the monoclonal outgrowth. In the monoclonal tumor (benign tumor), a somatic event, here partial chromosomal deletion, removes the remaining normal gene from a cell. In nonhereditary tumors, two successive somatic mutations must occur, a process that takes a longer time. By either pathway, the cell, deprived of growth-regulating influence from this gene, has unregulated growth and becomes a tumor. An important contribution from studies on the genetic origin of parathyroid carcinoma has been the realization that the mutations involve a different pathway than that involved with the benign gland enlargements. The Rb gene, a tumor-suppressor gene located on chromosome 13q14, was initially associated with retinoblastoma but has since been implicated in other neoplasias, including parathyroid carcinoma. Early studies implicated allelic deletions of the Rb gene in many parathyroid carcinomas and decreased or absent expression of the Rb protein. However, because there are often large deletions in chromosome 13 that include many genes in addition to the Rb locus (with similar findings in some pituitary carcinomas), it remains possible that other tumor-suppressor genes on chromosome 13 may be playing a role in parathyroid carcinoma. Of special importance was the discovery that, in some sporadic parathyroid cancers, germ-line mutations have been found; this, in turn, has led to careful investigation of the families of these patients and a new clinical indication for genetic testing in this setting. Hypercalcemia occurring in family members (who are also found to have the germ-line mutations) can lead to the finding, at parathyroid surgery, of premalignant parathyroid tumors. Deletions in the Rb gene locus may play an additional role in pathogenesis of parathyroid cancer, as well as other still uncharacterized genetic defects. In some parathyroid adenomas, activation of a protooncogene has been identified. Signs and Symptoms Half or more of patients with hyperparathyroidism are asymptomatic. In series in which patients are followed without operation, as many as 80% are classified as without symptoms. Manifestations of hyperparathyroidism involve primarily the kidneys and the skeletal system. With earlier detection, renal complications occur in <20% of patients in many large series. In occasional patients, repeated episodes of nephrolithiasis or the formation of large calculi may lead to urinary tract obstruction, infection, and loss of renal function. X-ray changes include resorption of the phalangeal tufts and replacement of the usually sharp cortical outline of the bone in the digits by an irregular outline (subperiosteal resorption). In recent years, osteitis fibrosa cystica has been very rare in primary hyperparathyroidism, probably due to the earlier detection of the disease. With the use of multiple markers of bone turnover, such as formation indices (bone-specific alkaline phosphatase, osteocalcin, and type I procollagen peptides) and bone resorption indices (including hydroxypyridinium collagen cross-links and telopeptides of type I collagen), increased skeletal turnover is detected in essentially all patients with established hyperparathyroidism. Similarly, bone density in the extremities can be quantified by densitometry of the hip or of the distal radius at a site chosen to be primarily cortical. After an initial loss of bone mass in patients with mild asymptomatic hyperparathyroidism, a new equilibrium may be reached, with bone density and biochemical manifestations of the disease remaining relatively unchanged.