Testicular function in males with infantile nephropathic cystinosis.

STUDY QUESTION: Do males with the rare lysosomal storage disease infantile nephropathic cystinosis (INC) have a chance of biological fatherhood? SUMMARY ANSWER: Cryostorage of semen could be an option for approximately 20% of young males with INC, with surgical sperm retrieval from the centre of the testes providing additional opportunities for fatherhood. WHAT IS KNOWN ALREADY: Biallelic mutations in the cystinosin (CTNS) gene in INC cause dysfunction in cystine transport across lysosomal membranes and cystine accumulation throughout the body. Spontaneous paternity in cystinosis has not been described, despite the availability of cysteamine treatment. Azoospermia has been diagnosed in small case series of males with INC. ART using ICSI requires few spermatozoa, either from semen or extracted surgically from the testes of azoospermic men. However, there is limited evidence to suggest this could be successful in INC. STUDY DESIGN, SIZE, DURATION: In this prospective cohort study performed between 2018 and 2019, we performed a cross-sectional investigation of 18 male patients with INC to delineate endocrine and spermatogenic testicular function. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum hormone levels, semen samples (according to World Health Organization 2010 standards), and testicular ultrasound images were analysed in 18 male patients aged 15.4-40.5 years. Surgical sperm extraction was performed in two, and their testicular biopsies were investigated by light and electron microscopy. Past adherence to cysteamine treatment was assessed from medical record information, using a composite scoring system. MAIN RESULTS AND THE ROLE OF CHANCE: Adherence to cysteamine treatment was high in most patients. Testicular volumes and testosterone levels were in the normal ranges, with the exception of two and three older patients, respectively. Serum LH levels were above the normal range in all subjects aged ≥20 years. FSH levels were elevated in all but four males: three with spermatozoa in semen and one adolescent. Inhibin B levels were shown to be lower in older men. Testicular ultrasound revealed signs of obstruction in 67% of patients. Reduced fructose and zinc seminal markers were found in 33%, including two patients with azoospermia who underwent successful surgical sperm retrieval. Histology identified fully preserved spermatogenesis in the centre of their testes, but also tubular atrophy and lysosomal overload in Sertoli and Leydig cells of the testicular periphery. LIMITATIONS, REASONS FOR CAUTION: Limitations of this study are the small number of assessed patients and the heterogeneity of their dysfunction in cystine transport across lysosomal membranes. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that testicular degeneration in cystinosis results from the lysosomal overload of Sertoli and Leydig cells of the testicular periphery, and that this can possibly be delayed, but not prevented, by good adherence to cysteamine treatment. Endocrine testicular function in INC may remain compensated until the fourth decade of life; however, azoospermia may occur during adolescence. Cryostorage of semen could be an option for approximately 20% of young males with INC, with surgical sperm retrieval providing additional opportunities for biological fatherhood. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Cystinosis Foundation Germany. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: n/a.

Phosphate wasting disorders in adults.

A cause of hypophosphatemia is phosphate wasting disorders. Knowledge concerning mechanisms involved in phosphate wasting disorders has greatly increased in the last decade by the identification of phosphatonins, among them FGF-23. FGF-23 is a primarily bone derived factor decreasing renal tubular reabsorption of phosphate and the synthesis of calcitriol. Currently, pharmacological treatment of these disorders offers limited efficacy and is potentially associated to gastrointestinal, renal, and parathyroid complications; therefore, efforts have been directed toward newer pharmacological strategies that target the FGF-23 pathway. This review focuses on phosphate metabolism, its main regulators, and phosphate wasting disorders in adults, highlighting the main issues related to diagnosis and current and new potential treatments.

Glycaemic variability in paediatric patients with type 1 diabetes on continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI): a cross-sectional cohort study.

OBJECTIVE: This cross-sectional observational cohort study was designed to investigate i) whether glycaemic variability in paediatric patients with type 1 diabetes is lower in those using an insulin pump (CSII) compared with those using multiple daily insulin injections (MDI) and ii) whether urinary F2 -isoprostanes and/or urinary prostaglandin F2 excretion as surrogate marker of oxidative stress and cyclooxygenase activity are associated with glycaemic variability. METHODS: 48 paediatric patients with type 1 diabetes (22 using an insulin pump) underwent an ambulatory 3-day continuous glucose monitoring. All patients continued with normal daily activities and collected urine for two consecutive 24 h periods. The glucose pentagon was used to calculate the glycaemic risk parameter. RESULTS: Insulin requirements, HDL-cholesterol, the mean of glycaemic excursions (P < 0·01) and the standard deviation of mean glucose concentration (P < 0·05) were significantly lower in patients with CSII compared with those using MDI. By contrast, averaged HbA1c during the last twelve months as well as at the time of sensor insertion did not differ significantly between both groups. Summarizing characteristic parameter of acute and long-term metabolic control into the glucose pentagon revealed a significantly lower glycaemic risk parameter in CSI patients compared with both, healthy subjects and patients using MDI (P < 0·05). CONCLUSIONS: Paediatric patients with type 1 diabetes using an insulin pump presented with lower glycaemic variability and a concomitantly lower glycaemic risk parameter compared with those using MDII. Whether these findings translate into a lower risk of diabetes associated cardiovascular complications remains to be elucidated.

Three-year growth hormone treatment in short children with X-linked hypophosphatemic rickets: effects on linear growth and body disproportion.

CONTEXT: Children with X-linked hypophosphatemic rickets (XLH) are prone to progressive disproportionate stunting despite oral phosphate and vitamin D treatment. OBJECTIVE: Our objective was to analyze the effects of GH treatment on stature and lengths of linear body segments in short children with XLH. DESIGN, SETTINGS, AND PATIENTS: A 3-yr randomized controlled open-label GH study in short prepubertal children with XLH (n = 16) on phosphate and calcitriol treatment was conducted. A cohort of XLH patients (n = 76) on conservative treatment served as an XLH reference population. MAIN OUTCOME MEASURES: Changes in SD scores (SDS) of stature and linear body segments, i.e. sitting height, leg and arm length, and sitting height index (i.e. ratio between sitting height and stature) were the main outcome measures. RESULTS: XLH patients presented at time of enrollment with significant impairments of stature (-3.3 SDS) and linear body segments compared with healthy children. Leg length (-3.8 SDS) was most impaired, whereas sitting height (-1.7 SDS) was best preserved. The markedly elevated mean sitting height index (+3.3 SDS) reflected severe body disproportion. GH resulted in a sustained increase in linear growth (stature, +1.1 SDS; sitting height, +1.3 SDS; leg length, +0.8 SDS; arm length, +1.1 SDS; each P < 0.05 vs. baseline), whereas no significant changes were observed in controls. Mean height SDS at 3 yr did not significantly differ between groups. Sitting height index remained stable in both the GH-treated patients and in study controls but increased further in the XLH-reference population. CONCLUSIONS: The 3-yr GH treatment improved linear growth without progression of body disproportion in short children with XLH.

Bone cell biology and pediatric renal osteodystrophy.

Patients with chronic kidney disease (CKD) show a broad spectrum of clinical symptoms intimately related to the disturbed mineral and bone metabolism and summarized as CKD-mineral-bone disorder (CKD-MBD). Whereas in adults an impaired bone metabolism translates mainly into an increased risk of fractures, in pediatric CKD patients rickets, skeletal deformations, and severe growth failure are additional and severe clinical findings. Further-more, an elevated Ca x P ion product, secondary hyperparathyroidism (sHPT) as well as concomitant calcitriol medication have been linked to ectopic (vascular) calcification, in which is strongly associated with the dramatically high cardiovascular morbidity and mortality even in pediatric CKD patients. Thus, in these patients the impaired mineral metabolism is the link between skeletal and cardiovascular disease. In other words, the complex interplay between kidney, skeleton, parathyroid gland, the intestine and the cardiovasculature is severely disturbed in CKD. This review summarizes the recent findings in our understanding of bone cell biology and alterations of mineral metabolism in children with CKD.

Differential effects of short-term growth hormone therapy on the cardiovascular risk profile in patients with chronic kidney disease: a pilot study.

Chronic kidney disease (CKD) is highly associated with an increased cardiovascular morbidity and mortality and is also a state of growth hormone (GH) resistance. We examined the impact of a short-term treatment with rhGH on circulating markers of cardiovascular risk in nonmalnourished CKD patients in a single-center, nonrandomized pilot study. Patients with stable CKD Stage 3 - 5 and age- and sex-matched healthy controls (n = 15 each) received a 7-day treatment with rhGH (1.33 mg/m2 body surface area per day, approximately 30 microg/kg). Prior to onset of rhGH therapy, at the end of the treatment period and at the end of a 7-day wash-out period blood was drawn to assess changes in circulating markers of cardiovascular risk. At time of enrollment CKD patients showed elevated serum concentrations of phosphate, calcium x phosphate product, PTH, fibroblast growth factor-23 (FGF-23), triglycerides, leptin and homocysteine compared to controls. In patients and controls rhGH treatment induced an increase in circulating insulin-like growth factor I (IGF-I), and the molar ratio of IGF-I/IGF binding protein 3 as well as an elevation of glucose, insulin, and triglycerides, whereas serum urea was decreased. In CKD patients, rhGH treatment raised concentrations of leptin, whereas LDL-cholesterol, homocysteine, phosphate, and 25-hydroxyvitamin D were significantly reduced. In controls, but not in CKD patients, rhGH raised 1,25-dihydroxy-vitamin D3 serum levels, which were even more elevated at the end of the wash-out period. In conclusion, short-term treatment with rhGH in CKD patients affects not only insulin and glucose metabolism but also affects serum lipid profile, i.e., LDL-cholesterol, leptin and homocysteine. Long-term trials are required to evaluate the impact of rhGH on cardiovascular morbidity and mortality.

PCB concentrations in lake trout (Salvelinus namaycush) are correlated to habitat use and lake characteristics.

This study considers the importance of lake trout habitat as a factor determining persistent organochlorine (OC) concentration. Lake trout is a stenothermal, cold water species and sensitive to hypoxia. Thus, factors such as lake depth, thermal stratification, and phosphorus enrichment may determine not only which lakes can support lake trout but may also influence among-lake variability in lake trout population characteristics including bioaccumulation of OCs. A survey of 23 lakes spanning much of the natural latitudinal distribution of lake trout provided a range of lake trout habitat to test the hypothesis that lake trout with greater access to littoral habitat for feeding will have lower concentrations of OCs than lake trout that are more restricted to pelagic habitat. Using the delta13C stable isotope signature in lake trout as an indicator of influence of benthic littoral feeding, we found a negative correlation between lipid-corrected delta13C and sigmaPCB concentrations supporting the hypothesis that increasing accessto littoral habitat results in lower OCs in lake trout. The prominence of mixotrophic phytoplankton in lakes with more contaminated lake trout indicated the pelagic microbial food web may exacerbate the biomagnification of OCs when lake trout are restricted to pelagic feeding. A model that predicted sigmaPCB in lake trout based on lake area and latitude (used as proximate variables for proportion of littoral versus pelagic habitat and accessibility to littoral habitat respectively) explained 73% of the variability in sigmaPCBs in lake trout in the 23 lakes surveyed.

Growth hormone treatment in short children with chronic kidney disease.

UNLABELLED: Growth hormone (GH) has been used for treatment of impaired growth in children with chronic kidney disease (CKD) for nearly 17 years. Controlled and open-label studies have shown that GH is highly effective in improving growth velocity and adult height. The growth response is negatively correlated with age and height at start and time spent on dialysis treatment; it is positively correlated with dose and duration of treatment and the primary renal disease (renal hypodysplasia). In children with renal transplants, corticosteroid treatment is an additional factor negatively influencing spontaneous growth rates. However, GH treatment is able to compensate corticosteroid-induced growth failure. GH treatment improved final height by 0.5-1.7 standard deviation score (SDS) in various studies, whereas the control group lost about 0.5 SDS in comparable time intervals. These variable results are explained in part by the factors mentioned above. The adverse events are comparable to those in non-CKD children treated with GH. CONCLUSION: GH treatment is safe and highly effective in improving growth and final height of short children with all stages of CKD. The highest treatment success is obtained if treatment is started at an early age and with relatively well-preserved residual renal function and continued until final height.

The metabolic fate of doubly stable isotope labelled heat-killed Lactobacillus johnsonii in humans.

OBJECTIVE: In this study, heat-killed Lactobacillus johnsonii (La1), doubly labelled with (13)C and (15)N (hk-dlLa1), was used to follow the metabolic fate after oral administration in humans. DESIGN: Experimental study. SETTING: University of Rostock, Children's Hospital, Research Laboratory. SUBJECTS: Ten healthy adults aged 23-26 years. INTERVENTION: The subjects received 74.6 mg/kg body weight hk-dlLa1 and 10 g alpha-D-raffinose together with breakfast. A sample of venous blood was taken after 2 h. Expired air samples were taken over 14 h, whereas urine and faeces were collected over a period of 48 h. (13)C- and (15)N-enrichments were measured by isotope ratio mass spectrometry. Hydrogen concentrations were measured by electrochemical detection. RESULTS: The orocaecal transit time (OCTT) was reached after 3.4 h. After 2 h, (13)C- and (15)N-enrichment of fibrinogen amounted to 2 and 25 p.p.m. excess, respectively. The (13)CO(2)-exhalation amounted to 9.2% of the ingested dose. The urinary excretion of (13)C and (15)N was 2.1 and 10.4% of the ingested dose, respectively, whereas the faecal excretion was 47.9 and 43.7% of the ingested dose, respectively. CONCLUSIONS: In comparison to OCTT of 3.4 h, both stable isotopes appear after 30 min in breath and urine, indicating that hk-dlLa1 is rapidly digested in the small bowel before reaching the caecum. This is confirmed by (13)C-and (15)N-enrichments of blood plasma fractions. The ingestion of hk-dlLa1 led to a (13)C- and (15)N-excretion of 59.2 and 54.1% of the ingested dose, respectively, of both stable isotopes.

Uremia-related vascular calcification: more than apatite deposition.

In the present study, we characterized and compared the mineral phase deposited in the aortic wall of two different frequently used chronic renal failure rat models of vascular calcification. Vascular calcification was induced in rats by either a 4-week adenine treatment followed by a 10-week high-phosphate diet or 5/6 nephrectomy followed by 6 weeks of 0.25 microg/kg/day calcitriol treatment and a high-phosphate diet. Multi-element mapping for calcium and phosphate together with mineral identification was performed on several regions of aortic sections by means of synchrotron X-ray-mu-fluorescence and diffraction. Bulk calcium and magnesium content of the aorta was assessed using flame atomic absorption spectrometry. Based on the diffraction data the Von Kossa-positive precipitate in the aortic regions (N=38) could be classified into three groups: (1) amorphous precipitate (absence of any diffraction peak pattern, N=12); (2) apatite (N=16); (3) a combination of apatite and magnesium-containing whitlockite (N=10). The occurrence of these precipitates differed significantly between the two models. Furthermore, the combination of apatite and whitlockite was exclusively found in the calcitriol-treated animals. These data indicate that in adenine/phosphate-induced uremia-related vascular calcification, apatite is the main component of the mineral phase. The presence of magnesium-containing whitlockite found in addition to apatite in the vitamin D-treated rats, has to be seen in view of the well-known vitamin D-stimulated gastrointestinal absorption of magnesium.

"Periodic fever" without fever: two cases of non-febrile TRAPS with mutations in the TNFRSF1A gene presenting with episodes of inflammation or monosymptomatic amyloidosis.

BACKGROUND: Tumour necrosis factor (TNF) receptor associated periodic syndrome (TRAPS) is caused by dominant mutations in the TNFRSF1A gene. In typical cases TRAPS begins early in childhood and is characterised by high and remittent fever over a period of 1-4 weeks or longer, accompanied by systemic and local inflammation. CASE REPORTS: Patient 1 presented with recurrent episodes of weakness, migrating myalgias, arthralgias, exanthema, and chest pain lasting for 1-4 weeks, but without any fever over an initial period of 4 years at least. Diagnosis of TRAPS was confirmed by the heterozygous mutation Y20H in TNFRSF1A. Patient 2, a 23 year old woman never had any symptoms indicative of TRAPS. Genetic evaluation of all members of her family with a TRAPS index patient disclosed the T50M mutation in TNFRSF1A. A medical check up showed proteinuria, and renal biopsy disclosed AA amyloidosis. CONCLUSIONS: TRAPS associated mutations can induce considerable inflammation that is not necessarily accompanied by fever. Even monosymptomatic severe amyloidosis can occur in these patients. Genetic counselling and appropriate management to prevent or mitigate amyloidosis may be necessary.

[Rickets. Diagnosis and therapy]. / Rachitis. Diagnostik und Therapie.

Rickets is caused by deficient mineralization at the level of growth plate and is usually due to a decreased serum calcium/phosphate product. Although the diagnosis of rickets can usually be suspected on the basis of a clinical examination (bone deformities in legs, impaired growth), radiological examination and detailed biochemical work-up are necessary to elucidate the etiology of the underlying disease. It is important to differentiate between calcipenic/vitamin deficient and phosphopenic rickets. The former is due to vitamin D deficiency, and the ultimate cause of this usually lies in altered vitamin D supply; however, impaired synthesis of or resistance to the actions of vitamin D can also be a cause. Phosphopenic rickets is usually related to impaired phosphate reabsorption in the proximal renal tubule. Both calcipenic and phosphopenic rickets can be acquired or hereditary in origin.

1,25(OH)2D3 and dihydrotestosterone interact to regulate proliferation and differentiation of epiphyseal chondrocytes.

Growth plate chondrocytes are affected by 1,25(OH)2D3 and androgens, which may critically interact to regulate proliferation and differentiation during the male pubertal growth spurt. We investigated possible interactions of 1,25(OH)2D3 and the non-aromatizable androgen dihydrotestosterone (DHT) in primary chondrocyte cultures from young male rats. DHT and 1,25(OH)2D3 independently stimulated DNA synthesis and cell proliferation in a dose-dependent manner with maximally effective doses of [10(-8) M] and [10(-12) M], respectively. Both DHT and 1,25(OH)2D3 stimulated the expression and release of IGF-I, and the proliferative effects of each hormone were prevented by an IGF-I antibody. DHT and 1,25(OH)2D3 increased messenger RNAs (mRNAs) of their cognate receptors and of IGF-I receptor mRNA (IGF-I-R). 1,25(OH)2D3 also stimulated mRNA of the androgen receptor (AR), whereas DHT did not affect mRNA of the vitamin-D receptor (VDR). Coincubation with both steroid hormones did not stimulate receptor mRNAs more than either hormone alone. The proliferative effects of DHT and 1,25(OH)2D3 were completely inhibited by simultaneous incubation with both hormones, despite potentiation of IGF-I synthesis. In contrast, both hormones synergistically stimulated cell differentiation as judged by alkaline phosphatase activity, collagen X mRNA, and matrix calcification in long-term experiments. We conclude that DHT and 1,25(OH)2D3 interact with respect to chondrocyte proliferation and cell differentiation. The proliferative effects of both hormones are mediated by local IGF-I synthesis. Simultaneous coincubation with both hormones blunts the proliferative effect exerted by either hormone alone, in favor of a more marked stimulation of cell differentiation.

Does recombinant growth hormone improve adult height in children with chronic renal failure?

During the past decade, the safety and efficacy of long-term treatment with recombinant human growth hormone (rhGH) in children with chronic renal failure before and after renal transplantation has been established. This article reviews the increasing evidence that rhGH treatment also results in a significant improvement of adult height in patients with childhood-onset chronic renal failure. The eventual height benefit of extended rhGH treatment appears to be 1.0 to 1.5 standard deviations on average. Whereas prepubertal rhGH treatment has a beneficial effect on final height, the efficacy of rhGH during puberty is less evident. The cumulative duration of rhGH treatment was found to be the most important positive, and the duration of dialysis treatment periods a negative predictor of rhGH efficacy, stressing the importance of prolonged rhGH treatment starting early in the course of chronic renal failure.

Analysis of cognitive and motor functioning during pubertal development: a new approach.

We investigated cognitive-motor abilities in 303 (156 female) school children from Zagreb, Croatia, in the age span 10 to 14 years using a newly developed chronometrical reactionmeter system (CRD). The following tests were applied: CRD-311 (simple visual discrimination of signal location), CRD-324 (short-term memory actualisation), CRD-21 (simple convergent visual orientation), and CRD-11 (arithmetically conceptualised/operationalised convergent thinking). In both gender a statistically significant age related improvement of the performance for time related parameters (minimum time of test item solving (MT), total ballast (TB), and total time of test solving (TT) was observed. In contrast, the number of errors (NE), which was the only non-time related parameter tested, did not significantly change with age. Significant differences between boys and girls were observed for the time related parameters TB and MT. TB was significantly lower in girls, whereas boys tended to be faster in MT measurements. In TT as a composed measure of the mentioned parameters, no major differences were observed. We conclude that the CRD system is a new useful tool for investigating the complexity of cognitive-motor abilities in children. Our cross-sectional study demonstrated that the time-related parameters were significantly affected by age and gender during puberty.

Long-term treatment with growth hormone in short children with nephropathic cystinosis.

OBJECTIVE: The objective was to assess the efficacy and safety of growth hormone (GH) treatment in severely growth retarded children with nephropathic cystinosis during conservative treatment and during renal replacement therapy. STUDY DESIGN: The design was an open-labeled prospective trial with a run-in period of 1 year. RESULTS: A total of 74 children with cystinosis (age 3.0 to 18 years) were treated with GH over a mean period of 3.1 years (range 1 to 10 years); 52 patients were receiving conservative treatment (mean age 7.1 years), 7 were receiving dialysis (12.5 years), and 15 had received a renal transplant (14.8 years). The mean standardized height (SD score) was -4.0 in the conservative treatment group, -4.4 in the dialysis group, and -4.9 in the renal transplant group. During the first treatment year, height velocity doubled in the conservative treatment group, increased by 80% in the dialysis group, and increased by 45% in renal transplant group. Within 3 years the height SD score increased by +1.6 (P <.001) in prepubertal patients receiving conservative treatment, and percentile parallel growth was maintained thereafter. These effects of GH were less expressed in peripubertal patients receiving renal replacement therapy. No major side effects were observed. CONCLUSION: Long-term GH treatment is safe and effective in young children with nephropathic cystinosis. GH treatment should be started early in the course of the disease if adequate nutrition and cysteamine treatment do not prevent growth retardation.

Effect of growth hormone treatment on the adult height of children with chronic renal failure. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

BACKGROUND: Growth hormone treatment stimulates growth in short children with chronic renal failure. However, the extent to which this therapy increases final adult height is not known. METHODS: We followed 38 initially prepubertal children with chronic renal failure treated with growth hormone for a mean of 5.3 years until they reached their final adult height. The mean (+/-SD) age at the start of treatment was 10.4+/-2.2 years, the mean bone age was 7.1+/-2.3 years, and the mean height was 3.1+/-1.2 SD below normal. Fifty matched children with chronic renal failure who were not treated with growth hormone served as controls. RESULTS: The children treated with growth hormone had sustained catch-up growth, whereas the control children had progressive growth failure. The mean final height of the growth hormone-treated children was 165 cm for boys and 156 cm for girls. The mean final adult height of the growth hormone-treated children was 1.6+/-1.2 SD below normal, which was 1.4 SD above their standardized height at base line (P< 0.001). In contrast, the final height of the untreated children (2.1+/-1.2 SD below normal) was 0.6 SD below their standardized height at base line (P<0.001). Although prepubertal bone maturation was accelerated in growth hormone-treated children, treatment was not associated with a shortening of the pubertal growth spurt. The total height gain was positively associated with the initial target-height deficit and the duration of growth hormone therapy and was negatively associated with the percentage of the observation period spent receiving dialysis treatment. CONCLUSIONS: Long-term growth hormone treatment of children with chronic renal failure induces persistent catch-up growth, and the majority of patients achieve normal adult height.

Message from the president: sexuality issues 2010.

PIP: This article offers 10 predictions concerning American sexuality in the next decade. About 50% of US teenagers will experience sexual intercourse in 2010. Young virgins participating in the abstinence-only-until-marriage program will experience a modest delay of 3-6 months in having sexual intercourse. In the year 2002, the US Congress will reauthorize this program. With puberty, pregnancy, HIV, and sexually transmitted disease prevention as their major focus, school-based sexuality education programs will be more prevalent, less controversial, and integrated into other topics. Moreover, people of all ages will increasingly refer to the Internet for information about sexuality issues. Facts about midlife and sexuality will increase as the baby boom generation gets old. Medical abortion and emergency contraception will change debates on abortion. A number of religious denominations will split over the issue of sexual orientation by 2002. While HIV/AIDS will wane in the US and Europe, other countries of the world will increasingly be destroyed by the epidemic. Finally, people in the next decade and beyond will continue to define sexuality in the context of relationships, intimacy, and pleasure.^ieng