Vesico-ureteric reflux, urinary-tract infection, and renal damage in children.
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Child↗
Biomedical subjects
I Gordon
Publications and source records attributed to I Gordon.
Developmental and age-related alterations in rat brain presynaptic dopaminergic mechanisms.
Age-related changes in both pre- and post-synaptic components of dopamine neurons have been demonstrated in humans as well as in animals. Our study was designed to examine the effects of age on presynaptic DA neurons. To assess the developmental changes in rat striatal dopamine carrier, we used [3H]GBR 12935, which binds selectively to this transporter. In addition we monitored changes in amphetamine- and KCl-induced [3H]DA release from rat striatal slices. We were able to demonstrate age dependent changes in DA transporter density, which reached a peak at age 3 months. Amphetamine-induced released of stored DA was exactly reversed, with a nadir at age 3 months. We assumed that the combination of low DA transporter level with increased transporter-mediated DA release may have a major compensatory role with respect to the maintenance of dopaminergic transmission during normal development, aging and neuro-degenerative diseases.
Age Factors↗
[3H]GBR 12935 labels mainly the piperazine acceptor site in the rat prefrontal cortex.
The binding characteristics of [3H]GBR 12935, a ligand for the dopamine (DA) transporter, have been extensively investigated in the striatum. The present study was designed to characterize [3H]GBR 12935-binding to prefrontal cortex (PFC) in rats. This region receives a dense DA input from the ventral tegmental area and is suspected to play a major role in higher associative functions. We demonstrated high-affinity, saturable, mazindol-sensitive [3H]GBR 12935-binding in the rat PFC; however, in contrast to the striatum, such binding was inhibited by increasing concentrations of Na+. This fact, together with the irregular pattern of the association kinetics and the marked sensitivity of [3H]GBR 12935-binding to piperazine derivatives, indicates the possible presence of more than one [3H]GBR 12935-binding site in the PFC. Furthermore, it appears that [3H] 12935 in the rat PFC labels mainly 'the piperazine acceptor site' and not the DA transporter.
Animals↗
Long-term effects of amygdaloid kindling on striatal dopaminergic terminals.
The present study assessed the effects of kindling on striatal DA terminals. Kindled and control rats were tested for DA transporter density using [3H]GBR-12935 binding to striatal membranes and for amphetamine and KCl-induced [3H]DA release from striatal slices. Kindling decreased the maximal number of [3H]GBR-12935 binding sites in the dorsal striatum of rats sacrificed either 2 h or 4 weeks after the last seizure but had no effect on stimulated fractional [3H]DA release. These findings suggest a minor damage to DA terminals in the dorsal striatum. At the same postseizure time points, kindling augmented the hyperlocomotion associated with novel environment. Explanation of this effect requires in vivo measures of striatal DA functioning.
Amygdala↗
Cervical cytology reported as negative and risk of adenocarcinoma of the cervix: no strong evidence of benefit.
The relationship between negative cervical cytology reports and risk of adenocarcinoma of the cervix was evaluated in a case-control study of 113 cases and 452 controls. All cases and controls had received at least two negative cytology reports. There was no significant difference between the cases and controls in the number of negative cytology reports or in history of cervical abnormality; while a test for trend in the time since last negative cytology report was significant (P < 0.001), the estimated benefit was very modest. Although the estimates of relative protection were higher in women aged less than 35 years than in women aged 35-69 years, this difference was not statistically significant. These results suggest that cervical screening as practised in the 1970s and 1980s was much less effective in preventing adenocarcinoma than squamous carcinoma of the cervix.
Adenocarcinoma↗
Absolute 99Tcm-DMSA renal uptake in children: optimum time to scan.
Absolute renal uptake was measured at 2, 4 and 6 h in 27 patients in order to determine a more convenient time for uptake compared with the 6-h measurement proposed by other authors. Measurements made at 2 and 4 h would need to be increased by 20 and 6%, respectively, to convert to the value at 6 h. Measurements at 4 h are a reasonable compromise to achieve a high-count/low-background image in a reasonable time and to obtain a good estimate of the predicted 6 h uptake at a single scanning session. The percent renal uptake at 6 h, U(6), can be derived from the percent uptake measured at t hours after injection, U(t), using the following formula: U(6) = U(t) x CF(t), where CF(t) = 1.0 + 0.03 (6 - t) for 4 < or = t < or = 6.
Adolescent↗
Children with intractable focal epilepsy: ictal and interictal 99TcM HMPAO single photon emission computed tomography.
Fourteen children with intractable complex partial seizures underwent ictal and interictal 99TcM HMPAO single photon emission computed tomography (SPECT) scans. Abnormalities concordant with clinical and/or EEG localisation were present in 13 of 14 ictal and/or interictal scans. Focal hyperperfusion was seen at the seizure focus on ictal scans and focal hypoperfusion was seen on interictal scans. The timing of the injection in relation to the start of the seizure was crucial for reliable localisation. While recognisable patterns of regional cerebral blood flow (rCBF) were seen on either interictal or ictal scans, marked changes in the patterns of rCBF between the ictal study and interictal study provided the most reliable information about seizure localisation. Using both ictal and interictal studies, 99TcM HMPAO SPECT may provide data about both the seizure origin and its relationship to structurally abnormal regions of the brain.
Adolescent↗
The effect of repeated amphetamine treatment on striatal DA transporter and rotation in rats.
The effect of repeated amphetamine treatment on the involvement of the striatal DA transporters in rotation behavior was tested in rats. Repeated amphetamine treatment had no effect on [3H]DA uptake or [3H]GBR-12935 binding density. However, unlike the naive rats who rotated away from the striatum with a lower density of DA transporters, rats sensitized to amphetamine rotated toward the striatum with a lower density of DA transporters. These findings imply that repeated amphetamine augments the subcortical involvement in behavioral output.
Animals↗
Cost to industry of illnesses related to alcohol and smoking. A study of Telecom Australia employees.
OBJECTIVE: To estimate the direct cost to industry of absenteeism attributable to drinking alcohol and smoking. DESIGN: Review of sick leave and superannuation data in the staff records of Telecom Australia (nearly 80,000 staff) for the financial year 1991-92 to identify illnesses related to alcohol or smoking. Costs were calculated by reference to tables of aetiological fractions, which statistically attribute a proportion of an illness to alcohol or smoking. MAIN OUTCOME MEASURE: The cost of employee absences attributable to alcohol or smoking expressed in the value of the person's daily salary. RESULTS: Illness attributable to smoking or alcohol accounted for 25% of sick leave. The estimated costs were $5,500,000 for alcohol and $16,500,000 for smoking. The total cost of $22,000,000 averages $275 per employee per year. If this cost is extrapolated to the rest of the Australian workforce, the total would exceed $2,000,000,000 a year. CONCLUSION: Limitations in the data mean that our results are likely to be underestimates. The direct costs to industry of ill health caused by alcohol and smoking are substantial and warrant preventive and rehabilitative programs.
Absenteeism↗
Effect of renal maturation on the clearance of technetium-99m mercaptoacetyltriglycine.
To investigate the effect of growth and maturation on the global kidney clearance of technetium-99m mercaptoacetyltriglycine (99mTc-MAG3), we investigated 509 children who attended for 99mTc-MAG3 renography in our department. In order to estimate the normal maturation of the kidney, only children who were classified as "normal" using diagnostic criteria were included in this study (n = 109). Kidney clearance was calculated using a gamma camera technique and a 20-min blood sample. There was a progressive increase in the clearance of 99mTc-MAG3 throughout childhood and into adolescence (mean clearance value below 2 month was 31.4 ml/min, mean clearance value above 12 years was 287 ml/min). When clearance was normalised to body surface area (BSA) a different pattern was seen, with a progressive increase from 3 weeks of age (mean value < 0.2 years: 208 ml/min/1.73 m2) to a plateau at the end of the first year of life (mean value > 2 years: 303 ml/min/1.73 m2). Maturation of the kidney as defined by the normalised clearance of 99mTc-MAG3 is therefore complete by the end of the 1st year of life, after which any change in non-corrected clearance values may be attributed to growth. To investigate the appropriate normalisation factor for 99mTc-MAG3 clearance in children, clearance values were compared to height, weight and BSA. The relationships were described using a linear model; the correlation coefficients demonstrated that BSA has the highest strength of relationship with 99mTc-MAG3 clearance. Body surface area may be used over 1 year of age to normalise the clearance values of 99mTc-MAG3.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[3H]GBR 12935 binding to human platelet membranes is sensitive to piperazine derivatives but not to dopamine uptake inhibitors.
It remains controversial whether blood platelet can be used as a peripheral model for the central presynaptic dopaminergic neurons. We investigated the existence of dopamine transport complex in human blood platelet membranes using the selective dopamine uptake inhibitor [3H]GBR 12935 as a radioligand. In contrast to [3H]GBR 12935 binding to rat striatal dopamine carrier site, the high affinity [3H]GBR 12935 binding to platelet membranes was insensitive to mazindol and other dopamine uptake inhibitors. Piperazine derivatives including GBR 12909 were found to be potent inhibitors of [3H]GBR 12935 binding to platelet membranes. [3H]GBR 12935, piperazine derivative-sensitive binding to platelet membranes was inhibited by increasing sodium concentration. Kinetic experiments revealed that both association and dissociation rates of [3H]GBR 12935 binding were slower to platelet membranes than to striatal membranes. These results indicate that [3H]GBR 12935 binding to platelet membranes is different from the binding of this ligand to the dopamine uptake complex and seems to label a "piperazine acceptor" site which was previously demonstrated in brain and liver membranes.
Animals↗
Successful in vivo immunolocalization of Langerhans cell histiocytosis with use of a monoclonal antibody, NA1/34.
The antibody NA1/34 is a murine monoclonal antibody directed against the CD1a surface antigen expressed on normal Langerhans cells, cortical thymocytes, and on lesional cells in Langerhans cell histiocytosis (LCH). Our hypothesis was that NA1/34 would localize sites of disease activity in patients with multisystem LCH. To test this hypothesis, indium 111-labeled NA1/34 was administered to five patients with multisystem LCH and serial gamma scans were obtained for up to 120 hours. Serial serum samples were obtained from one patient for analysis of anti-mouse Ig antibody and NA1/34 levels. Direct and indirect immunofluorescence staining for CD1a and NA1/34 were performed on a tissue biopsy specimen from one patient after administration of the antibody. The 1- and 4-hour scans showed distribution of antibody in the blood pool, but in later scans localization of the antibody was noted in areas of known disease activity in all five patients. Bony lesions, previously seen on skeletal radiographs, were especially well identified. Serum kinetics studies showed clearance of the antibody from the blood pool within 12 hours of administration. Direct binding of NA1/34 to lesional cells was demonstrated by direct immunofluorescence. The only adverse effect was urticaria in one patient. We conclude that NA1/34 localizes disease activity in vivo in bones of patients with LCH with minimal toxic effects. An evaluation of its role in determining disease extent ("staging") and in treatment is now needed.
Adult↗
Improving the accuracy of 99Tcm-mercaptoacetyltriglycine clearance by using two blood samples instead of one? Paediatric Task Group of the EANM.
From a database of 133 patients (98 children and 35 adults) who underwent multiple blood sampling for 99Tcm-mercaptoacetyltriglycine (MAG3) clearance, we determined simplified algorithms allowing the estimation of clearance. A one-compartment model with two blood samples was applied. The best choices for the adult population were the 12 and 90 min blood samples, giving a standard error of the estimate (S.E.E.) of less than 10 ml min-1 1.73 m-2; for the children, the 10 and 80 min blood samples gave a S.E.E. of 20 ml min-1 1.73 m-2; for both the adults and the children, the 10 and 70 min blood samples gave the best results with, however, a S.E.E. of 19 ml min-1 1.73 m-2. The use of such a combined algorithm will therefore result in a degradation of the results in adults, suggesting that a separate algorithm for each group is preferable. We compared the accuracy of the two blood sample method to the one blood sample method based on previously published algorithms for children and adults, respectively. The S.E.E. was significantly lower, in adults as well as in children, using the empirical two blood sample method. This two blood sample method seems potentially useful for routine practice in adult patients. The advantages of using such a method in children is balanced by the practical problems inherent in the need to take a second blood sample during the first 10 min, at a time when the plasma activity is rapidly decreasing.
Adult↗
Mercapto-acetyltriglycine (MAG 3) renography and indirect radionuclide cystography in posterior urethral valves.
OBJECTIVE: To assess dynamic isotope renography with 99mTc-labelled mercapto-acetyltriglycine (MAG 3) in conjunction with indirect radionucleide cystography (IRC) in the follow-up of boys with posterior urethral valves. PATIENTS AND METHODS: Fifty-one boys (95 renal units; mean age = 89 months, range 65-118) with previously treated posterior urethral vales underwent MAG 3 renography followed by IRC. Glomerular filtration rate (GFR) was estimated from the plasma clearance of 51Cr-ethylenediamine tetra-acetic acid following single intravenous injection. Renographic parameters noted were renal function based on the quality of renal visualization and background activity as well as renal drainage and the appearance of isotope in ureter and bladder. Following the dynamic 20 min MAG 3 renogram the child was allowed to leave the department and to return when he wished to void. IRC was then performed. Diuretics were not administered. RESULTS: Initial drainage from 30 kidneys was normal, in 36 drainage was delayed and in 25 drainage did not occur during the renogram phase. In four kidneys function was so poor as to preclude assessment. After the IRC, drainage was noted in 17 of 25 units which had not drained during the renogram, six units did not drain and in two drainage was equivocal due to the presence of vesico-ureteric reflux. The quality of the scan was good or very good in 42 patients (mean GFR = 92 ml/min/1.73 m2 SA) and moderate or poor in nine patients (median GFR = 20 ml/min/1.73 m2 SA) (P < 0.001). A residual urine was noted following micturition in 35 boys; this was due to incomplete bladder emptying in 14 and to immediate secondary refilling from dilated upper tracts in the remainder. CONCLUSION: IRC in conjunction with traditional dynamic renography using MAG 3 provides valuable additional information about upper tract drainage. The necessity for diuresis renography is obviated in the majority of patients. IRC also allows an excellent non-invasive, physiological assessment of both upper and lower urinary tract function which is superior to conventional single examination techniques. We recommend the use of MAG 3 with IRC in the routine follow-up of boys with posterior urethral valves.
Child↗
CD1 antibody immunolocalisation in Langerhans' cell histiocytosis.
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Antibodies, Monoclonal↗
Effect of posture on regional ventilation in children.
Little information has been published concerning the pattern of regional ventilation in children, yet many differences in lung and chest wall mechanics in childhood, supported by clinical observation, have led to the hypothesis that the pattern of regional ventilation seen in children may not be the same as in adults. Forty-three children and 16 adult volunteers underwent Krypton (Kr) 81m radionuclide ventilation lung scans in the supine and right and left decubitus postures. In children aged 2-10 years mean fractional ventilation to the right lung (VfR) was 46.1%. This fell to 36% when dependent and rose to 56.1% in the uppermost position. Redistribution of ventilation away from the dependent towards the uppermost lung was seen in all children. In children aged 10-18 years VfR was 57.2% (supine), 48.0% (dependent), and 62.9% (uppermost). An identical pattern was seen in children with normal or abnormal pulmonary function tests (peak expiratory flow rate, and FEV1: FVC ratio). In subjects over 18 years of age a different pattern was seen: mean VfR was 52.4% (supine), rising to 53.4% (dependent), and falling to 48.9% (uppermost). Postural redistribution of ventilation, as assessed by Kr81m ventilation imaging, changes late in the second decade of life. This will have clinical consequences in the management of children with unilateral lung disease.
Adolescent↗
Urinary endothelin (ET1) in complete ureteric obstruction in the miniature pig.
Segmental renal scarring occurs in experimental obstructive uropathy in the multipapillary porcine kidney, and segmental abnormalities in renal perfusion are likely to be responsible. This preliminary study examines the urinary excretion of the potent locally active vasoconstrictor endothelin 1 (ET 1) in a pig model of renal obstruction and subsequent relief. Significant urinary excretion of ET 1 from the postobstructive kidney was found to occur after longstanding obstruction. Preglomerular arteriolar stenosis may be the cause of the renal ischaemia in obstruction that is at first reversible but later becomes irreversible if the stimulus persists. ET 1 may be implicated in the pathogenesis of this injury.
Animals↗
Vesico-ureteric reflux in the damaged non-scarred kidney.
Renal damage without scarring is a rare manifestation of reflux nephropathy, and is infrequently reported in the literature. A retrospective review of a large series of patients with urinary tract disorders at the hospital for Sick Children, Great Ormond Street, identified 12 patients with vesico-ureteric reflux (VUR) with no evidence of scarring but with renal damage as assessed using technetium 99m dimercaptosuccinic acid (99mTc-DMSA) scan. There were 9 simplex kidneys, the differential function was between 33% and 43% (mean 38%). On follow-up to date (mean 6.7 years) all kidneys show stable differential function with neither improvement nor deterioration. Only 8 children had a urinary tract infection. Renal damage without evidence of a focal scar associated with VUR may be a manifestation of growth arrest possibly due to glomerular damage. The sensitivity of 99mTc-DMSA may reveal the permanent nature of the renal damage.
Child↗