Chronic renal failure in children.

Seventy-seven children with chronic renal failure were examined at one hospital in the province of Quebec between 1970 and 1975; this represents an incidence of 2.5 per million population per year. The entities responsible for chronic renal failure were urinary tract malformation (in 36%), chronic glomerulonephritis (in 22%), congenital renal parenchymal malformation (in 21%) and hereditary nephropathy (in 13%). The evolution of chronic renal failure in children with either vesicoureteral reflux or a posterior urethral valve seemed to be related more to the initial severity of the disease than to the age at the time of diagnosis. Hence any screening program designed to detect kidney disease in schoolchildren would not prevent chronic renal failure, since at that age renal parenchymal damage seems to be irreversible. The manner in which chronic glomerulonephritis evolved depended on whether the nephrotic syndrome was present and on the type of histologic lesion. Children with congenital renal hypoplasia or dysplasia often presented with seizures due to hypertensive encephalopathy without obvious symptoms or signs of pre-existing renal disease. Among patients with familial nephropathy many of those with cystinosis underwent successful renal transplantation early in life.     

Disruption of ROBO2 is associated with urinary tract anomalies and confers risk of vesicoureteral reflux

Congenital anomalies of the kidney and urinary tract (CAKUT) include vesicoureteral reflux (VUR). VUR is a complex, genetically heterogeneous developmental disorder characterized by the retrograde flow of urine from the bladder into the ureter and is associated with reflux nephropathy, the cause of 15% of end-stage renal disease in children and young adults. We investigated a man with a de novo translocation, 46,X,t(Y;3)(p11;p12)dn, who exhibits multiple congenital abnormalities, including severe bilateral VUR with ureterovesical junction defects. This translocation disrupts ROBO2, which encodes a transmembrane receptor for SLIT ligand, and produces dominant-negative ROBO2 proteins that abrogate SLIT-ROBO signaling in vitro. In addition, we identified two novel ROBO2 intracellular missense variants that segregate with CAKUT and VUR in two unrelated families. Adult heterozygous and mosaic mutant mice with reduced Robo2 gene dosage also exhibit striking CAKUT-VUR phenotypes. Collectively, these results implicate the SLIT-ROBO signaling pathway in the pathogenesis of a subset of human VUR.     

Opioid receptors: Some perspectives from early studies of their role in normal physiology,stress responsivity,and in specific addictive diseases

The early history of research on the possible existence of specific opioid receptors and on developing a new form of pharmacotherapy for the treatment of heroin addiction in New York City, from 1960–1973, along with the special relationships between two leading scientists conducting these research efforts, Dr. Eric Simon and Dr. Vincent P. Dole Jr., are presented in a historical perspective. The linkage of these early efforts and the subsequent identification and the elucidation of the effects of exogenous opiates acting at specific opiate receptors in human physiology, including some findings from perspective studies of heroin addicts at time of entry to and during methadone maintenance treatment, are presented in the context of the important clues which thereby were provided concerning the possible roles of the endogenous opioids in normal mammalian physiology. From many of these early clinical research findings and studies in animal models, the hypothesis that the endogenous opioids system may play an important role in stress responsivity was formulated along with the related hypothesis, first presented in the early 1970s, that an atypical responsivity to stress and stressors might be involved in the acquisition and persistence of, and relapse to specific addictive diseases, including heroin addiction, cocaine dependency and alcoholism. More recent studies of the possible involvement of the specific opioid receptors in these three addictive diseases—heroin addiction, cocaine addiction and alcoholism—from our laboratory are discussed in a historical perspective of the development of these ideas from the early research findings of not only Dr. Eric Simon, but his numerous colleagues in opioid research in the United States and throughout the world. Special issue dedicated to Dr. Eric J. Simon.     

The earliest cases of human immunodeficiency virus type 1 group M in Congo-Kinshasa, Rwanda and Burundi and the origin of acquired immune deficiency syndrome

The early cases of acquired immune deficiency syndrome and human immunodeficiency virus type 1 (HIV-1) infection in the 1960s and 1970s in Congo-Kinshasa (Zaire), Rwanda and Burundi are reviewed. These countries appear to be the source of the HIV-1 group M epidemic, which then spread outwards to neighbouring Tanzania and Uganda in the east, and Congo-Brazzaville in the west. Further spread to Haiti and onwards to the USA can be explained by the hundreds of single men from Haiti who participated in the UNESCO educational programme in the Congo between 1960 and 1975.     

An experimental model of ascending pyelonephritis due toCandida albicans in rats

We developed a new experimental model of ascendingCandida pyelonephritis in female rats with leukopenia and vesicoureteral reflux. Rats were treated transperitoneally with cyclophosphamide (200 mg/kg) to induce leukopenia 3 days before and transurethrally with diluted acetic acid solution to induce vesicoureteral reflux 1 day before inoculation ofCandida albicans strain, ATCC 10259 (containing 10⁷ cells). Microscopy revealed acute pyelonephritis in whichCandida cells invaded from the fornix and/or papilla into the medulla within 3 days after inoculation. Between 7 and 28 days after inoculation, chronic pyelonephritis reached the cortex. The incidence of pyelonephritis increased gradually and was approximately 80% after 7 days.Candida colony counts of bladder urine specimens obtained by direct puncture were significantly greater in rats with pyelonephritis extending into the parenchyma than in those with pyelonephritis located along the pelvis (p<0.01). These results suggest that this rat model shows the characteristic feature of ascending pyelonephritis due toC. albicans and that the severity ofCandida pyelonephritis can be estimated fromCandida counts of bladder urine.     

Climatic regime shifts and decadal-scale variability in calanoid copepod populations off southern California

Decadal‐scale climatic regimes and the shifts between them have important impacts on marine ecosystems. Climatic regime shifts have been observed or hypothesized in the North Pacific basin in 1976–77 and 1989. This paper examines long‐term (1951–99) trends in calanoid copepod populations off southern California, and the evidence for responses to regime shifts. Most of the species of calanoid copepod that were analysed underwent one or more step changes during the 49 years covered by the study. All but one of these changes occurred in five periods: the late 1950s, late 1960s, mid‐1970s, early 1980s and around 1990. The late 1960s changes are considered to be artifacts of an increase in sampling depth. Strong El Niño conditions affected California waters during the late 1950s and early 1980s. The step changes of the mid‐1970s and late 1980s to early 1990s may have been responses to regime shifts or other climatic events. 28% of the species and subspecies responded to the 1976–77 event, all increasing in abundance. Another 28% of the copepod categories underwent step changes around 1990, most decreasing. Evidence for regime shifts in the hydrographic variables that were examined is mixed. The 10‐m temperature increased in the mid‐1970s. Abrupt changes in variables around 1990 were short‐lived. However, the population responses around 1990 and to the El Niños of the late 1950s and early 1980s indicate that some species of calanoid copepods may respond on longer time scales to environmental conditions that persist only a few years.     

Congenital malformations in Japanese macaques (Macaca fuscata) at Takasakiyama

From the late 1960s to the early 1970s, many congenitally malformed infants were born into provisioned Japanese macaque troops. Although the exact cause of this problem was not determined, the occurrence of malformations decreased thereafter. We examined possible factors such as total population size, number of adult females, birth rate, and volume of provisioned food. Agrichemicals attached to provisioned food are suspected as the main cause, as other factors were found to have no influence. Many more malformations were seen in males compared with females, in feet compared with hands, and in the fourth compared with other digits. We confirmed that the frequency of congenital malformation was high during the 1960s through to the mid-1970s when increased levels of provisioned food were given and that the incidence of congenital malformations was also elevated among wild macaques during this time.     

The role of Tamm-Horsfall protein in the pathogenesis of reflux nephropathy and chronic pyelonephritis

Recurrent bacterial infection of the kidney was previously thought to be responsible for the renal scarring typical of chronic pyelonephritis until recent studies suggested that recurrent bacteriuria rarely produces chronic pyelonephritis in the absence of obstructive uropathy. In contrast, the association between vesicoureteral reflux (VUR) and chronic pyelonephritis has been observed frequently in the absence of urinary infection. Although the mechanism by which VUR injures the kidney has not been defined, recent observations have suggested that some component of urine might serve as an antigenic determinant involved in the immunopathogenesis of renal scarring in VUR. Therefore, the present studies investigated the immunopathogenic role of Tamm-Horsfall protein (THP) in (1) a rabbit model of tubulointerstitial nephritis; (2) a swine model of reflux nephropathy; and (3) patients with recurrent nephrolithiasis. The antigenic similarities between THP and uropathic bacteria were also studied. Our observations indicate that autoimmune responses to THP may occur after exposure to THP by intravenous challenge in rabbits, by urinary reflux in pigs, and in recurrent nephrolithiasis in man. Also, extracts of uropathic coliforms competitively inhibit the binding of human THP to its antibody. These studies suggest that autoimmune responses to THP may be the pathogenetic mechanism by which these factors, including bacteriuria, contribute to "chronic pyelonephritis."     

Hand‐held,clinical dual mode ultrasound ‐ photoacoustic imaging of rat urinary bladder and its applications

Urinary bladder imaging is critical to diagnose urinary tract disorders, and bladder cancer. There is a great need for safe, non‐invasive, and sensitive imaging technique which enables bladder imaging. Photoacoustic imaging is a rapidly growing imaging technique for various biological applications. It can be combined with clinical ultrasound imaging system for hand‐held, dual modal ultrasound‐photoacoustic real‐time imaging. Structural (bladder wall) and functional (accretion of nanoparticles) bladder imaging is shown here with combined ultrasound and photoacoustic imaging in rats. Photoacoustic images of bladder wall is shown using black ink as the contrast agent. Chicken tissues were stacked on the abdomen of the animal to demonstrate the feasibility of photoacoustic imaging till a depth of 2 cm. Also, the feasibility of photoacoustic imaging for a common bladder disorder, vesicoureteral reflux is studied using urinary tract mimicking phantom. It is also shown that a clinical ultrasound system can be used for photoacoustic imaging of non‐invasive clearance study of gold nanorods from circulation by monitoring the gradual accumulation of the gold nanorods in the bladder. The time taken for accumulation of nanorods in the bladder can be used as an indicator of the clearance rate of the nanoparticle circulation from the body.      

Expansion pathways of the exotic common reed (Phragmites australis): a historical and genetic analysis

Using 779 herbarium and modern specimens, we reconstructed the spread of the common reed ( Phragmites australis ) in Quebec, Canada, where large-scale invasion of this plant species has been reported since the 1960s. All specimens were genetically differentiated using molecular tools to identify the genotype (native or exotic). The exotic genotype (haplotype M) has been present in Quebec as early as 1916, but it was rare prior to the 1970s and was almost exclusively restricted to the shores of the St. Lawrence River. The exotic genotype spread inland only after the beginning of the 1970s. In less than 20 years, a complete shift occurred, from the dominance of native genotypes to the dominance of the exotic genotype. Today, more than 95% of common reed colonies found in Quebec are dominated by the haplotype M. It is especially abundant along roads, but colonies present in marshes are also dominated by the exotic genotype. This study provides evidence that, in Quebec, the development of the highway network in the 1960s and 1970s strongly contributed to the inland expansion of the exotic genotype. Moreover, it shows the usefulness of molecular techniques for reconstructing the spread of an invader. Without the use of molecular tools, the reconstruction of invasions of exotic taxa would be impossible because of the lack of clear phenotypic differences between genotypes.     

Retrospective study of children with renal scarring associated with reflux and urinary infection.

OBJECTIVE--To review the histories of children with bilateral renal scarring and severe vesicoureteric reflux to determine whether an improvement in early management might reduce the risk of scarring. DESIGN--Retrospective study of medical records and discussion with parents. SETTING--Outpatient departments of two teaching hospitals. PATIENTS--52 children aged 1-12 years participating in a randomised comparison of medical and surgical management. All had a history of symptomatic urinary tract infection. Two thirds presented with fever and two with hypertension or renal failure. In only one out of 32 children examined by antenatal ultrasonography was an abnormality suspected. RESULTS--There was delay in diagnosis or appropriate imaging or effective treatment of urinary infection in 50 of the 52 children. In 41 there was delay in diagnosis; there was delay in treating a confirmed infection in 45; no antibacterial prophylaxis was prescribed before imaging in 28; and investigation of the urinary tract was delayed in 33. The severity of scarring was significantly related to delay in diagnosis (chi 2 for trend 7.43, P = 0.01). Four children of mothers known to have reflux nephropathy were not investigated until they developed urinary tract infection. CONCLUSIONS--Efforts to reduce the incidence and severity of renal scarring should be directed towards rapid diagnosis and effective early management of urinary tract infection in infancy and childhood. Siblings and offspring of known patients with severe reflux nephropathy should be investigated for reflux.     

Historical population size of the harbour seal,Phoca vitulina,in the Delta area,SW Netherlands

Seals in the Dutch Delta area have been subject to hunting pressure for centuries, promoted by a bounty system which generated a sort of hunting statistics. Hunting mortality is used to estimate historical population size. Based on ranges for most likely net recruitment rates, corresponding population trajectories are back calculated from an assessed population size of 350 seals in 1960. It is concluded that the size of the harbour seal population in the Delta area in 1900 will have been close to 11 500 animals. Significant loss of habitat has occurred due to closing off parts of the larger estuaries and the enlargement of the entrance to the harbour of Rotterdam in the 1960s and early 1970s. It is estimated that about 4000 harbour seals could inhabit the remaining Delta area under tidal influence. This outcome, based on retrospective population analysis, will be an important reference in defining management objectives for the recovery of the harbour seal population in the Delta area, which amounted to 18 seals in 1992.     

Diseases causing end-stage renal failure in New South Wales.

The nature of the original renal disease was determined in 403 consecutive cases of end-stage renal failure, in 317 of which the clinical diagnosis was corroborated by histological examination of the kidney. Five diseases accounted for 20 or more cases--glomerulonephritis (31% of the total), analgesic nephropathy (29%), primary vesicoureteral reflux (8%), essential hypertension (6%), and polycystic kidneys (5%). In only four cases did renal failure result from chronic pyelonephritis without a demonstrable primary cause. Greater use of micturating cystography and cystoscopy and routine urine testing for salicylate are advocated for earlier diagnosis of the major causes of "pyelonephritis". The incidence of end-stage renal failure in people aged 15-55 in New South Wales was estimated to be at least 34 new cases per million of total population each year.     

Urinary tract infections in children. An update.

Urinary tract infection is a common and frequently recurring condition in children. The susceptibility of the host, the presence of urinary tract abnormalities, and the virulence of the urinary pathogens are of primary importance in the development of the infection. Renal parenchymal scarring, hypertension, and renal insufficiency are well-established complications of the infection in children. To reduce the risk of renal damage, diagnosis and treatment must be prompt. The diagnosis demands radiologic evaluation of the urinary tract in all boys, all children younger than 5 years, all patients with voiding dysfunction, and school-aged girls with recurrent infection to identify those patients with vesicoureteral reflux, obstruction, or other urinary tract abnormalities. Both voiding cystourethrography and renal ultrasonography are the initial examinations to use to determine the next appropriate study. Children with vesicoureteral reflux or with recurrent urinary tract infections should receive prophylactic antibiotic therapy and should be observed closely to prevent renal scarring.     

Fertility change in Costa Rica 1960-84: analysis of retrospective lifetime reproductive histories

Lifetime reproductive histories of a 1984-85 nationally representative sample of 870 women aged 25-59 years provided data to describe the evolution of fertility, contraception, breast-feeding, and natural fecundability in Costa Rica between 1960 and 1984. The contraceptive prevalence rate increased from 23% in 1965 to 58% in 1975 and 66% in 1984. Duration of breast-feeding was stable during the 1960s, decreased in the early 1970s, and increased after about 1976. Fecundability among women who did not practise contraception was lower than expected and declined between 1960 and 1975, probably because of selection effects. Despite a high consistency between estimations from the reproductive histories and other sources of data, some suggestion of omissions of short periods of contraceptive use in the distant past was detected. The survey may have reduced recall errors by using a calendar that summarizes major life events together. The analysis demonstrated the feasibility and usefulness of asking for lifetime reproductive histories in fertility surveys in developing countries.     

Official Hunting Patterns, and Trends in the Proportions of Sika (

Records of official deer control operations in the Kaweka Range between 1958 and 1988 have been used to describe the pattern of official hunting, to indicate changes in hunting efficiency, and to show trends in the proportions of sika and red deer in sympatric populations. The pattern of hunting largely reflected wild animal control priorities, and to some extent the resources available. Whereas hunting effort was concentrated in Block 1 (of three) during the 1960s to protect catchment values, changes in the rationale for wild animal control and the efforts of commercial and recreational hunters in the more accessible areas led to a more even spread of the hunting effort from the early 1970s. Hunting efficiency also varied between the three h unting blocks, probably reflecting differences in the ease with which particular habitats could be hunted. A decline in hunting efficiency over the study period was interpreted as an overall decrease in the density of the deer population. The proportion of sika among the deer shot in the Kaweka Range has increased steadily from about 10-20% in the early 1960s to 70% in 1987-88. A competitive advantage over red deer because of their different digestive physiology is suggested as the main reason. The most rapid increases in the proportion of sika were associated with two Peaks in commercial venison and live-capture operations that concentrated on red deer, indicating that commercial hunting has also been a factor. It is likely that sika will continue icreasing in proportion to red deer in areas already inhabited. In addition, sika will probably continue to disperse into new areas as they competitively displace red deer.     

Purinergic signalling: Its unpopular beginning, its acceptance and its exciting future

Adenosine 5'-triphosphate (ATP) was identified in 1970 as the transmitter responsible for non-adrenergic, non-cholinergic neurotransmission in the gut and bladder and the term 'purinergic' was coined. Purinergic cotransmission was proposed in 1976 and ATP is now recognized as a cotransmitter in all nerves in the peripheral and central nervous systems. P1 (adenosine) and P2 (ATP) receptors were distinguished in 1978. Cloning of these receptors in the early 1990s was a turning point in the acceptance of the purinergic signalling hypothesis. There are both short-term purinergic signalling in neurotransmission, neuromodulation and secretion and long-term (trophic) purinergic signalling of cell proliferation, differentiation and death in development and regeneration. Much is known about the mechanisms of ATP release and its breakdown by ectonucleotidases. Recently, there has been emphasis on purinergic pathophysiology, including neurodegenerative and neuropsychiatric disorders. Purinergic therapeutic strategies are being developed for treatment of gut, kidney, bladder, lung, skeletal and reproductive system disorders, pain and cancer.     

Changes in the timing of births in Melbourne, Australia

2 10-year marriage cohorts from 2 surveys of married women in Melbourne were compared on their timing of the 1st and 2nd births. The results showed that women who were married in the early 1970s were much more likely to delay their first birth until about the 3rd or 4th year of marriage compared with women who married in the 1960s. This tendency to delay the 1st birth was probably aided by effective contraception, as it coincided with widespread use of the oral contraceptive. There was no difference in the timing of the 2nd birth in relation th the 1st birth between the 2 marriage cohorts. Women who delayed childbearing also preferred smaller families. Indeed, the increase in the % of women delaying childbearing appears to be synonymous with the trend toward the two-child family. Altough the number of married women in the labor force increased significantly from the early to the later cohort, a desire to work was not usually cited as the reason for delaying childbearing. Rather, economic reasons were most frequently mentioned for delaying childbearing.