Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption.

Epithelia permit selective and regulated flux from apical to basolateral surfaces by transcellular passage through cells or paracellular flux between cells. Tight junctions constitute the barrier to paracellular conductance; however, little is known about the specific molecules that mediate paracellular permeabilities. Renal magnesium ion (Mg2+) resorption occurs predominantly through a paracellular conductance in the thick ascending limb of Henle (TAL). Here, positional cloning has identified a human gene, paracellin-1 (PCLN-1), mutations in which cause renal Mg2+ wasting. PCLN-1 is located in tight junctions of the TAL and is related to the claudin family of tight junction proteins. These findings provide insight into Mg2+ homeostasis, demonstrate the role of a tight junction protein in human disease, and identify an essential component of a selective paracellular conductance.

The influence of hyperparathyroidism on glucose metabolism in uremia.

We studied glucose metabolism in a group of adolescents and young adults with uremia using the hyperglycemic clamp technique. In eight adolescent patients, the glucose metabolic rate correlated negatively with PTH levels and positively with the glomerular filtration rate. Six patients, one adolescent and five adults on regular hemodialysis with severe hyperparathyroidism, had low glucose metabolic rates and reduced insulin sensitivity compared to normal subjects. After parathyroidectomy, the glucose metabolic rate improved by 47%; plasma insulin concentrations during hyperglycemia increased by 37%, and insulin sensitivity did not change significantly. Thus, correction of hyperparathyroidism was associated with normalization of glucose metabolic rates and increased insulin secretion, but insulin resistance did not change.

Evidence for disturbed regulation of calciotropic hormone metabolism in gitelman syndrome.

Little attention has been paid to interactions between circulating levels of calcium, PTH, and 1,25-dihydroxycholecalciferol [1,25(OH)2D] and bone mineral density in primary renal magnesium deficiency. Plasma and urinary electrolytes, and circulating levels of calciotropic hormones were studied in 13 untreated patients with primary renal tubular hypokalemic alkalosis with hypocalciuria and magnesium deficiency. The blood ionized calcium concentration was significantly lower in patients than in controls. Despite this fact, PTH and 1,25-(OH)2D levels were similar in both groups of subjects. The negative linear relationships between PTH and ionized calcium, which significantly differed between Gitelman patients and healthy subjects in terms of intercept; the negative relationship between ionized calcium and 1,25-(OH)2D, which was comparable in both groups; and the positive relationship between 1,25-(OH)2D and PTH, which was identical in both groups, point both to a blunted secretion of PTH induced by magnesium depletion and to the lack of interference of the latter with the activation of 1 alpha-hydroxylase by PTH. The similar bone mineral density at the lumbar spine by dual energy x-ray absorptiometry in 11 patients and 11 healthy subjects argues against chronically sustained negative calcium balance.

Hemophagocytic lymphohistiocytosis in a patient with deletion of 22q11.2.

We report on a new patient with deletion of 22q11 associated with hemophagocytic lymphohistiocytosis and a fatal outcome. She had minor facial anomalies and cardiac malformation corresponding to those described in del (22q11) syndrome, normal T and B cell function and NK activity; bone marrow aspiration showed active erythrophagocytosis. Our case in addition to two other children reported previously suggest that such a rare association between lymphocyte-macrophage activation and deletion of 22q11 may be more frequent than previously recognized.

Percutaneous treatment of gas-containing lumbar disc herniation. Report of two cases.

A limited number of cases have been reported in which gas-containing lumbar disc herniation caused compression of nerve roots. The authors describe two patients in whom computerized tomography scanning revealed a large intraspinal gas collection that appeared to be causing nerve root compression and that was successfully evacuated by percutaneous needle aspiration.

Genotype-phenotype correlations in normotensive patients with primary renal tubular hypokalemic metabolic alkalosis.

Among the different forms of hereditary renal tubulopathies associated with hypokalemia, metabolic alkalosis and normotension, two main types of disorders have been identified: Gitelman disease, which appears to be a homogeneous post-Henle's loop disorder, and Bartter syndrome, a heterogeneous Henle loop disorder. A specific gene has been found responsible for Gitelman disease, encoding the thiazide-sensitive Na-Cl cotransporter (TSC) of the distal convoluted tubule. From a phenotypic point of view the characteristic findings of this disease are hypocalciuria, hypomagnesemia and tetanic crises appearing during childhood or later. Many subjects are asymptomatic. At least three different genes have been shown to be responsible for Bartter syndrome, characterized by mutations in the proteins encoding respectively the bumetanide-sensitive Na-K-2Cl cotransporter, the inwardly-rectifying renal potassium channel and a renal chloride channel, all protein transports located in the ascending limb of Henle's loop. Mutations in the first two transport proteins have been demonstrated in patients with the hypercalciuric forms of Bartter syndrome associated with nephrocalcinosis (respectively Bartter syndrome type I and II), who were often born after pregnancies complicated by polyhydramnios and premature delivery. Mutations in the gene encoding a renal chloride channel were recently recognized in patients with a Henle tubular defect not associated with nephrocalcinosis (Bartter syndrome type III). Most of the latter group of patients were normo-hypercalciuric and presented dehydration and life-threatening hypotension in the first year of life. However, these three genes do not explain all the patients with Bartter syndrome which unlike Gitelman disease, appears to be a very heterogeneous disorder. Clearance studies, especially if done during furosemide and/or hydrochlorothiazide administration, have been helpful in identifying the site of tubular involvement. Considering both phenotypic and genotypic data, we propose a clinical-pathophysiological and molecular approach to diagnose the different tubulopathies associated with hypokalemic metabolic alkalosis.

Ex novo episodes of acute glomerulonephritis and Guillain-Barré syndrome: a case report.

A nine-year-old girl had several ex novo episodes of acute glomerulonephritis with clinical evidence of rapid progression in two of them. Guillain-Barré syndrome was diagnosed 10 days after the second episode of acute glomerulonephritis. Two renal biopsies (performed at about a four-year interval) gave morphological evidence of new episodes of acute glomerulonephritis. To our knowledge this is the first report of an association between ex novo episodes of acute glomerulonephritis and Guillain-Barré syndrome.

Intraplatelet serotonin (I5HT) in children with the hemolytic uremic syndrome.

I5HT levels were investigated in 14 children with Hemolytic Uremic Syndrome (HUS). Low levels of I5HT were demonstrated in all the children studied during the early phase of the disease, indicating reversible platelet aggregation and recirculation of degranulated platelets. Three months after the onset of HUS, only 2 children with a pathological picture of cortical necrosis and a mild degree of chronic renal failure had low I5HT levels. On the contrary, normal I5HT levels were present in the other children completely recovered from HUS and with a renal biopsy picture of thrombotic microangiopathy with predominant glomerular involvement. We conclude that normal values of I5HT, after the acute stage of HUS, are a good index of complete recovery from the disease. Further observations are required to assess the prognostic value of low I5HT levels in children with chronic renal failure secondary to HUS.

Mineral metabolism during a hemofiltration session in children.

We studied the effects of one session of hemofiltration on the mineral metabolism in a group of uremic children. We observed an increase of calcemia, accompanied by positive calcium balance, and a decrease of plasma phosphate and PTH-MM. No substantial loss of plasma 25-OH D was found. It is concluded that hemofiltration has a positive effect on calcemia and is very effective in removing phosphate, but it acts only temporarily on PTH removal. An adequate calcium concentration must be provided in the substitution fluid.

[Radiotherapy of brain tumors in childhood]. / Radioterapia dei tumori cerebrali nell'infanzia.

External radiotherapy with high energy photons in children's brain tumors improves results of surgical treatment according to their histology. Radiotherapy treatment is a decisive factor in survival time and quality of life. Undifferentiated tumors with high radiosensitivity are treated when radiotherapy is the only means for recovery; tumors presenting histologically low malignancy in which effective radiotherapy treatment is uncertain and the risk of radiotherapy damage is the predominant factor. Radiotherapists who treat children's brains which in many cases are not yet totally myelinized , must have good technical ability. Literature and personal experience show that in medulloblastomas irradiation of the entire central nervous system associated with chemotherapy gives a survival time of 5 years in 50% of the cases; in glioblastomas and anaplastic astrocytomas, fortunately rare in children, results are poor; in brainstem tumors the association of the extracranial shunt to radiotherapy has improved results of survival time at 5 years to 50%. A good quality of life is frequent and radiological effects are rare. It is clear that radiotherapy has reached its maximum. Progress is still to be made thanks to discoveries of more effective radiosensitizer or radioprotector compounds.

Fever phobia among Italian caregivers: a survey in a pediatric emergency department.

AIM: The aim of this study was to compare caregivers' knowledge and management of fever in an Italian Pediatric Emergency Department and to determine whether caregivers of a single child or those whose child had a history of chronic illness report greater symptoms of "fever phobia". METHODS: A questionnaire was used to survey caregivers of children who visited pediatric emergency department. of the Milano-Bicocca University Medical Center at San Gerardo Hospital, Monza, Italy. The study was carried out in winter, from December 2012 to January 2013. RESULTS: A total of 98 responses were analyzed. Italian caregivers measure fever at longer intervals and fewer of them wake their children to administer antipyretics. Forty-five percent of caregivers either do not give evidence-based treatment, or do administer drugs more frequently than recommended. No differences emerge between caregivers of a single child or multiple children. Caregivers in the chronic illness group do consider lower temperatures to possibly cause complications, although they state they are less concerned about possible complications resulting from it. Furthermore this subgroup tends to use pediatric emergency units more frequently. CONCLUSION: Caregivers aggressively administer antipyretics or take the child to the Pediatric Emergency Department in case of fever. Having an only child is not clearly associated with fever phobia. History of chronic illness calls for consideration in further studies to explore it as a trigger factor to fever phobia.

Kinetics of furosemide in children with chronic renal failure undergoing regular haemodialysis.

Furosemide was measured by gas-liquid chromatography in blood and dialysis fluid from 7 children with chronic renal failure, undergoing regular haemodialysis. It was administered chronically, in two or three daily doses (4.2-9.4mg/kg). Two children received 1 mg/kg intravenously for determination of the pharmacokinetics. The half-life was longer than in adults and in anephric patients on haemodialysis. Systemic and renal clearance were also much lower. Plasma protein binding in 2 out of 6 cases was reduced as compared to normal adults. The data do not suggest any need to modify the present dosage schedule despite the 4-5 fold increase in the half-life of furosemide. The contribution of haemodialysis to drug clearance was minimal, and accounted for less than 10% of the total clearance.

Seizures and transient blindness following intravenous pulse methylprednisolone in children with primary glomerulonephritis.

Two children, 1 with idiopathic nephrotic syndrome and 1 with endo-extracapillary glomerulonephritis, presented an episode of seizures and transient blindness at different times after i.v. pulse methylprednisolone (IVPMP) treatment. Neurological manifestations in patient 1 could be due to hypertension secondary to IVPMP, while the pathogenesis of such manifestations remained difficult to clarify in patient 2. The severity of uremia in patient 2 could be one of the conditions that, in association with the abrupt changes obtained with IVPMP, predispose to neurological manifestations. Careful clinical and biochemical monitoring seems necessary in children with primary glomerulonephritis, other than those transplanted, after IVPMP, and factors predisposing to neurologic sequelae should be further defined.

Renal tubular function in children and adolescents with Gitelman's syndrome, the hypocalciuric variant of Bartter's syndrome.

Renal tubular function was studied in 14 patients with Gitelman's syndrome and 14 control subjects. Apart from the biochemical hallmarks of Gitelman's syndrome, namely alkalaemia, hyperbicarbonataemia, hypokalaemia, hypomagnesaemia (with increased magnesium over creatinine ratio), increased urinary chloride over creatinine ratio, and low urinary calcium over creatinine, the patients were found to have hyperproteinaemia, hypochloraemia, high total plasma calcium concentration, reduced plasma ionized calcium concentration, and high urinary sodium excretion. A statistically significant negative linear relationship between plasma magnesium concentration and magnesium excretion corrected for glomerular filtration was observed in patients. The fractional calcium clearance and the urinary excretion of calcium corrected for glomerular filtration was significantly decreased in patients. In patients the urinary osmolality after overnight water deprivation ranged from 526 to 1067 mmol/kg. Glucosuria and aminoaciduria were similar in patients and controls. The results of the study demonstrate the renal origin of hypomagnesaemia and hypocalciuria in Gitelman's syndrome. The failure to demonstrate hyperaminoaciduria, hyperglucosuria, hyperphosphaturia, hyperuricosuria, and severely impaired urinary concentrating ability provide evidence for a defect residing in the distal convoluted tubule.

Growth evaluation in children with acute renal failure of unknown etiology.

We performed a retrospective study on 47 children over 1 year of age with severe acute renal failure (ARF) treated with hemodialysis (HD) at our Center from 1978 to 1986 in order to evaluate the diagnostic and prognostic value of growth indexes at hospital admission as a criterion to distinguish cases of ARF without previous chronic renal failure (CRF) from cases in which CRF was not previously diagnosed. The age of the patients ranged from 17 months to 13 years. The cause of ARF was identified in 41 children; 5 of them remained on HD for different reasons (hemolytic uremic syndrome with arteriolar involvement in 3 cases; renal vein thrombosis in 1; endoextracapillary glomerulonephritis in 1). No apparent cause of ARF was found in the other 6 children who remained on chronic HD. A careful history showed that these 6 children had had uremic symptoms for many years. When height was expressed as height standard deviation score (HSDS), the 6 children with ARF of unknown etiology showed significantly lower HSDS values compared with the other 41 children in whom a cause of ARF was diagnosed (p less than 0.001). In conclusion, growth failure in children requiring HD for ARF of unknown etiology is an important criterion that suggests a previously undiagnosed CRF and thus consequently a negative long-term prognosis.