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Biomedical subjects

P Cuckow

Publications and source records attributed to P Cuckow.

9 recordsLinked to original sources

Ca2+ regulation in detrusor smooth muscle from ovine fetal bladder after in utero bladder outflow obstruction.

PURPOSE: We characterized intracellular Ca(2+) regulation in fetal bladders following outflow obstruction by examining the Ca(2+) response to agonists in smooth muscle cells. MATERIALS AND METHODS: Severe bladder outflow obstruction was induced in male fetal sheep by placing a urethral ring and urachal ligation midway through gestation at 75 days. Fetuses were examined 30 days after surgery. Intracellular Ca(2+) in single smooth muscle cells isolated from the bladder wall was measured with epifluorescence microscopy using fura-2(AM) during exposure to agonists, such as carbachol and adenosine triphosphate, and to other activators, such as caffeine and KCl. RESULTS: Detrusor smooth muscle cells from obstructed bladders had resting intracellular Ca(2+) similar to that in sham operated controls. The maximal response to carbachol was decreased following obstruction (p <0.05). Construction of dose-response curves also demonstrated higher EC(50) (p <0.05). However, these changes were not mirrored by caffeine evoked Ca(2+) release, which was not significantly different between the obstruction group and sham operated controls. Kinetic analysis of carbachol transients further revealed an attenuated maximal rate of increase in obstructed bladders (p <0.01). The magnitude of intracellular Ca(2+) to purinergic neurotransmitter adenosine triphosphate was also found to be smaller in cells from obstructed bladders (p <0.05), although transmembrane influx by high K depolarization was not significantly affected. CONCLUSIONS: Muscarinic and purinergic pathways were down-regulated in fetal detrusor muscle following outflow obstruction. These major functional receptors appeared to be more susceptible to obstruction than other Ca(2+) regulators. Their impairment may contribute to the compromised contractile function seen in in utero bladder outflow obstruction.

Animals↗

Ca2+ regulation in detrusor smooth muscle from developing fetal sheep bladders.

Sheep fetus is a useful model to study in utero bladder outflow obstruction but little is known about cell physiology of fetal bladders. To remedy this defect we have characterised intracellular Ca(2+) regulation in fetal sheep myocytes of different developmental ages. Fetal detrusor myocytes had a similar resting [Ca(2+)](i) to adult cells and exhibited transient [Ca(2+)](i) increases in response to carbachol, ATP, high-K, caffeine and low-Na. The carbachol transients were abolished by atropine and caffeine; the ATP response was blocked by alpha,beta-methylene ATP; high-K-evoked [Ca(2+)](i) rises were antagonised by verapamil. The maximal responses to carbachol, high-K, caffeine and low-Na in fetal cells were similar to those of adult counterparts, whilst the ATP response was smaller (p < 0.05). These variables were largely similar between the three gestational groups with the exception of ATP-induced response between early fetal and adult bladders (p < 0.05). Dose-response curves to carbachol demonstrated an increase of potency between mid-gestation and early adulthood (p < 0.05). These data show that muscarinic receptors coupled to intracellular Ca(2+) release, P2X receptor-linked Ca(2+) entry, depolarisation-induced Ca(2+) rise via L-type Ca(2+) channels, Na(+)/Ca(2+) exchange and functional intracellular Ca(2+) stores are all operational in fetal bladder myocytes. Whilst most of Ca(2+) regulators are substantially developed and occur at an early fetal age, a further functional maturation for cholinergic sensitivity and purinergic efficacy continues throughout to adulthood.

Adenosine Triphosphate↗

Renal primitive neuroectodermal tumor in childhood with intracardiac extension.

Primary primitive neuroectodermal tumors of the kidney are exceptionally rare and usually affect children and young adults. We report the first pediatric case of renal primitive neuroectodermal tumor presenting with tumor extension along the inferior vena cava to the right ventricle. This case highlights that when considering a renal tumor with significant intravascular extension in the pediatric age group, although the most likely diagnosis remains Wilms tumor, other rare entities may also demonstrate similar clinical and imaging features.

Child, Preschool↗

The management of paediatric urolithiasis.

OBJECTIVE: To evaluate the efficacy and safety of the management of paediatric urolithiasis by extracorporeal shock wave lithotripsy (ESWL), endoscopic ureterolithotomy, percutaneous nephrolithotomy (PCNL) and open nephrolithotomy. PATIENTS AND METHODS: In a 3-year period (1997-1999), 59 children were treated for urolithiasis and underwent a total of 79 procedures. Thirty-two ESWL sessions were performed in 23 children (mean age 7.4 years, median 6.0). PCNL was undertaken in 30 renal units in 25 children (mean age 6.4 years, median 4.0). Eight patients (mean age 7.8 years, median 5) underwent 17 ureteroscopic procedures, six of which involved the use of a holmium laser. Three children with staghorn calculi underwent open nephrolithotomy under conditions of renal ischaemia and hypothermia. RESULTS: Of the 23 children treated using ESWL, 21 (91%) became stone-free; 17 underwent one ESWL session (74%), three had two sessions and three (13%) had three sessions. All eight patients who underwent ureteroscopy became stone-free. Four patients in whom the stone could not be reached by ureteroscopy initially had a JJ stent inserted, and the stone and stent subsequently removed. Stones were cleared using PCNL in 27 of 30 renal units (90%); three patients who had residual stone fragments were rendered stone-free by ESWL. Two of three children undergoing open nephrolithotomy were stone-free after surgery and the remaining one rendered stone-free with ESWL. Metabolic evaluation showed that 25 of 45 children (55%) had a urinary infection, eight (18%) had hyperoxaluria, three (7%) had hypercalciuria, two (4%) had cystinuria, and no identifiable cause was found in seven (16%). Treatment by a single modality rendered 52 of the 59 children (88%) stone-free; when the different modalities were combined, 57 of 59 patients (97%) were cleared of their stones. CONCLUSIONS: Technological advances in ESWL, ureteroscopy and PCNL have had a significant effect on the management of urolithiasis in children, allowing a safe and successful outcome. The comprehensive care of children with urolithiasis should include a full metabolic evaluation. Anatomical anomalies contribute to the complexity of many cases, necessitating a close liaison between adult and paediatric urologists, nephrologists and radiologists to optimize stone management in children.

Adolescent↗