Stabilization of acetylcholine receptors at the neuromuscular synapse: the role of the nerve.

The majority of acetylcholine receptors (AChRs) at innervated neuromuscular junctions (NMJs) are stable, with half-lives averaging about 11 days in rodent muscles. In addition to the stable AChRs, approximately 18% of AChRs at these innervated junctions are rapidly turned over (RTOs), with half lives of less than 24 h. We have postulated that RTOs may be precursors of stable AChRs, and that the motor nerve may influence their stabilization. This hypothesis was tested by: (i) labeling AChRs in mouse sternomastoid (SM) muscles with 125I-alpha-BuTx; (ii) denervating one SM muscle in each mouse, and (iii) following the fate of the labeled AChRs through a 5-day period when RTOs were either stabilized or degraded. The hypothesis predicts that denervation should preclude stabilization of RTOs, resulting in a deficit of stable AChRs in denervated muscles. The results showed a highly significant (P less than 0.002) deficit of stable AChRs in denervated as compared with innervated muscles. Control experiments excluded the possibility that this deficit could be attributed to independent accelerated degradation of either RTOs or pre-existing stable AChRs. The observed deficit was quantitatively consistent with the deficit predicted by a mathematical model based on interruption of stabilization following denervation. We conclude that: (i) the observed deficit after denervation of NMJs is due to failure of stabilization of pre-existing RTOs; (ii) RTOs at normally innervated NMJs are precursors of stable AChRs; (iii) stabilization occurs after the insertion of AChRs at NMJs, and (iv) motor nerves play a key role in stabilization of RTOs. The concept of receptor stabilization has important implications for understanding the biology of the neuromuscular junction and post-synaptic plasticity.

Transient gall bladder dilatation associated with hypokalaemia in a patient with Bartter syndrome.

A 5.5-month-old male infant with hypokalaemia and gall bladder dilatation is reported. The child was shown to have Bartter syndrome. After oral treatment with potassium and indomethacin, serum potassium levels became low normal and the gall bladder enlargement resolved. This entity should be included in the clinical spectrum of neuromuscular disturbances resulting from hypokalaemia and should be considered in a hypokalaemic infant with a right-sided abdominal mass.

The immune status of uraemic children/adolescents with chronic renal failure and renal replacement therapy.

In adults with chronic renal failure (CRF) and/or renal replacement therapy (RRT) various immunological abnormalities have been described, but few data are available for the paediatric age group. We performed basic in vitro immunological studies in 26 patients 10 months-19 years of age with advanced renal failure, 11 with CRF (creatinine clearance 16.8 +/- 5.2 ml/min per 1.73 m2), 15 on RRT with haemodialysis (HD; n = 9) and continuous ambulatory peritoneal dialysis (CAPD; n = 6) as well as in 16 healthy controls. None had clinical evidence of deranged immune function. No significant differences were found in the percentages of B- and T-cells, T-cell subsets CD3, CD4, CD8 and mitogenic responses to phytohaemagglutinin and concanavalin A (Con A) between RRT patients (HD = CAPD) and control children. Most parameters in CRF patients were also normal, although they had a low percentage of B-cells (12.1 +/- 4.1; RRT: 19.7 +/- 6.5; controls: 18.5 +/- 7.1; P less than 0.01), relatively low levels of serum immunoglobulin G (948.4 +/- 209.4 mg/dl; HD: 1374.7 +/- 235.2 mg/dl; P less than 0.01; CAPD: 966.3 +/- 430.2 mg/dl, NS) and a high normal response to Con A (34.3 +/- 13.6 cpm x 10(-3); RRT: 24.5 +/- 11.3 cpm x 10(-3); controls: 23.4 +/- 9.9 cpm x 10(-3), P less than 0.01). All these values were, however, well within the normal accepted range. These data indicate that children/adolescents with CRF and/or RRT have no significant basic in vitro immunological defects. This study did not test the functional immune status of the young uraemic patients.

Skin and mucosal lesions associated with cyclosporin A therapy: report of a case.

A 16-year-old boy developed bullous lesions on fingers, ears, tongue, and buccal mucosa as well as cauliflower-like growths on the epiglottis and vocal cords 1 1/2 years after a second renal transplantation and exposure to sunlight while receiving cyclosporin A (CsA). Withdrawal of CsA was followed by complete resolution of skin and mucosal lesions. A predisposition for adverse reactions to CsA is suggested, as additional side effects of CsA therapy were also present.

Vaccination against hepatitis B in children and adolescent patients on dialysis.

Twenty-one children and adolescent patients, 2-19 years of age, on renal replacement therapy were immunised at monthly intervals with three doses of 20 micrograms hepatitis B vaccine (Heptavax B, Merck Sharp & Dohme). In the absence of seroconversion, vaccination was continued with monthly doses of 40 micrograms hepatitis B vaccine until antibody to hepatitis B surface antigen became positive. The rate of seroconversion increased from 33.3% (7 of 21) to 76.1% (16 of 21) and 85.6% (18 of 21) with three, four and five vaccine injections respectively. Three patients had no immune response despite six to seven vaccine dosages; they had previously received immunosuppressive therapy. Antibody titres measured 1 year after seroconversion were found to be within the protective range (85-2500 mIU/ml). These results show that the impaired immune response to hepatitis B vaccination in young dialysis patients can be overcome by increasing the number of injections and the dose of the vaccine. Protective antibody titres are maintained for at least 1 year after vaccination. Immunosuppressive therapy may interfere with the vaccine response.

Immunoregulation with levamisole in children with frequently relapsing steroid responsive nephrotic syndrome.

The immunological and clinical effects of levamisole were studied in 10 children with frequently relapsing steroid responsive nephrotic syndrome (SRNS). The efficacy of the drug was tested during remission of the disease with all patients on alternate day steroid therapy. The lymphocyte proliferative response to phytohemagglutinin (PHA), concanavalin-A (Con-A) and pokeweed mitogen (PWM) were normal. The Con-A induced suppressor T-lymphocyte activity of 7 patients was low before treatment with levamisole 8 +/- 3.7% and increased to normal values during therapy 34 +/- 6%; p less than 0.001 (control 32 +/- 5%). In these 7 children prednisolone dosage could be decreased significantly or discontinued altogether (44.1 +/- 5.3%). Patients without immunoregulatory abnormalities did not respond to levamisole. In 3 out of 4 children tested the percentage of OKT8+ cells rose during levamisole therapy from 19.7 +/- 2.1 to 37 +/- 2.3 (p less than 0.001), thus correcting the elevated pre-treatment OKT4+/OKT8+ ratio from 3.1 +/- 0.2 to 1.5 +/- 0.2; p less than 0.001 (control 1.47 +/- 0.2). These data support the hypothesis that abnormal immunoregulation may play a role in the pathogenesis of SRNS. Treatment with levamisole can be useful in some patients with the frequently relapsing form of the disease.

Recurrence of oxalate deposition in a renal transplant during ciclosporin A therapy.

A 14.5-year-old boy with end-stage renal failure due to familial primary hyperoxaluria underwent cadaver donor renal transplantation. The graft function was stable for a period of 22 months, while he was on conventional immunosuppressive therapy (prednisolone and azathioprine) and additional oral pyridoxine, phosphorus, and magnesium supplementation. When ciclosporin A was introduced instead of azathioprine, the blood levels of oxalate rose, and oxalate deposition in the renal tubuli became evident. These observations suggest that ciclosporin A interferes with oxalate metabolism and, therefore, should be given with utmost caution in patients with primary hyperoxaluria.

Cerebral atrophy and nephropathic cystinosis.

The management of end stage renal failure in cystinotic children is correlated with a longer survival, sometimes complicated with neurological abnormalities. Cranial computed tomography was performed in 10 patients and showed a significant atrophy; the pathogenesis of this damage remains unclear.

Pulmonary calcifications in children on dialysis.

Pulmonary calcifications are known to occur in patients with chronic renal failure. Recently, scintigrams with bone-seeking radionuclides have been used to detect subclinical pulmonary calcium deposits. We studied 18 children on maintenance dialysis without evidence of pulmonary calcification on chest X-ray. Four children (22.2%) had a positive technetium 99m hydroxymethylene diphosphate scan (group 1), and 14 children had a negative scan (group 2). Mean serum aluminum levels were 2.68 +/- 0.30 mumol/l (mean +/- SD) in group 1 as compared to 1.66 +/- 0.72 in group 2 (p less than 0.01). No significant difference was found between the groups with respect to serum levels of calcium, phosphorus, bicarbonate, magnesium and the calcium-phosphorus product as well as parathyroid hormone and vitamin D levels. The patients with pulmonary calcifications were on dialysis a significantly longer time than those of group 2 (62 +/- 15 versus 35.7 +/- 23 months; p less than 0.01). These data show that pulmonary calcification occurs with high frequency in children undergoing long-term dialysis. They seem to be related to high serum aluminum levels. We propose that pulmonary scintigrams with bone-seeking radionuclides be used routinely for the diagnosis and follow-up of uremic pulmonary calcification.

Modification of peritoneal ultrafiltration capacity in children undergoing peritoneal dialysis.

Eleven children (7 girls and 4 boys) 2 1/2 to 17 years and 8 months of age were treated with CAPD for periods ranging from 6 to 31 months. All children were treated with commercially available dialysate solutions containing lactate. Peritoneal ultrafiltration capacity (PUFC) decreased progressively in all children without accompanying decrease in peritoneal urea and creatinine clearances. Five children developed membrane failure with negative ultrafiltration. One episode of peritonitis occurred in one of these 5 children and in 4 of them only 1.5% glucose solutions had been used. After an initial period (ranging from 14 to 31 months) of CAPD, 2 children were treated with Intermittent Ambulatory Peritoneal Dialysis (IAPD) and two others with Intermittent Cycling Peritoneal Dialysis (ICPD). In these 4 children, PUFC increased within one month from -3.75 ml/kg/day to + 5 ml/kg/day. By providing a shorter dwell time, IAPD and ICPD may allow a reduction in net inward transport of glucose, the maintenance of osmolar gradient and preservation of ultrafiltration capacity. Furthermore, periods of rest may allow some recovery from the progressive deterioration of the peritoneum resulting from long-term irrigation of the peritoneal cavity. These results indicate that IAPD and CPD may be superior to CAPD to maintain the ultrafiltration capacity of the peritoneum.

Treatment of idiopathic nephrotic syndrome with levamisole.

Thirty children with frequently relapsing idiopathic nephrotic syndrome (INS) were treated with levamisole (2.5 mg/kg BW) twice a week for a mean period of 9.9 months. A beneficial effect was observed in 16 children in whom corticosteroids could be significantly decreased without relapse. Levamisole was ineffective in 14 patients. There was no difference between the two groups in the duration of INS, the number of relapses and the duration of treatment with levamisole. The mean age at onset of INS was higher in the group of patients where levamisole was effective (5.8 years versus 2.8 years). In 7 patients who responded to levamisole neutrophils decreased below 4 X 10(9)/l. Transient granulocytopenia was observed in 3. It is concluded that levamisole may be effective in frequently relapsing INS with minimal side effects.

Excretory urography and cystourethrography in the evaluation of children with urinary tract infection.

One hundred and ninety-one children with a first episode of urinary tract infection (UTI) underwent intravenous pyelography (IVP) and voiding cystourethrography (VCU). Only three children (1.5%) had positive findings in the IVP that were of prognostic significance and were confined to that particular investigation alone. In contrast, 97 (50.7%) of the VCUs showed anatomical abnormalities. Vesico-ureteral reflux (VUR) of varying grades was diagnosed in 77 children (40.3%). These findings stress the importance of radiological investigation of the urinary tract after the first incidence of UTI, but suggest that IVP will give information of therapeutic and/or prognostic value in a small number of cases.

Natural history of an acute glomerulonephritis epidemic in children. An 11- to 12-year follow-up.

During an epidemic of poststreptococcal acute glomerulonephritis (PSAGN) in Israel during the second half of 1968, 155 children were hospitalized. All of them were initially followed up for 6 mo to 2 yr, during which period no evidence of continuing kidney damage was found. Fifty-five of the group were hospitalized over the next 2 to 10 yr for reasons unrelated to their original illness, at which time they also were found to be free of renal damage. Eighty children were examined 11 to 12 yr after the epidemic, and in them, too, urine examination, blood chemistry and blood pressure were within normal limits. It seems reasonable to conclude that the PSAGN of the 1968 epidemic was a benign disease with no lasting ill effects. Since most of the cases were associated with an M-55 skin Streptococcus and pyoderma, we suggest that glomerulonephritis due to pyoderma associated with this strain does not give rise to chronic renal disease.

Effects of sociodemographic and attitudinal factors on mother-initiated medication behavior for children.

Little is known about the therapies that people initiate for their health problems, and the available research on self-medication has focused primarily on adult populations. Only a few studies have specifically addressed mothers' independent use of medications for their children, and none has described such behavior in depth (for example, relating-perceived symptoms and conditions in the child or attempting to provide an explanation for mothers' decisions in these situations). A stratified systematic random sample of 100 mothers of children between 6 months and 12 years old was obtained at each of 3 pediatric ambulatory care clinics. Mothers were interviewed about their use of medications for their children, their concerns about their children's health, and their medication-related attitudes. The study results suggest that income and education are related to the types of medication and medical appliances mothers keep to treat the various health problems of their children. Mothers' perceptions of their children's potential susceptibility to health problems are related to possession of what they believe are relevant remedies for those problems (as well as to keeping a greater variety of medications on hand). Socioeconomic status appears to be one determinant of the number of different remedies (and especially the number of different medical appliances) that are purchased. Certain attitudes held by mothers about medications also play a role in explaining how great a variety of remedies are kept available for children in the event that they become ill, and these medication-related attitudes are highly correlated with socioeconomic status.

[Urolithiasis in Isreali children (author's transl)]. / la lithiase urinaire de l'enfant en Israël.

Sixty-eight children (ages ranging from 5 months to 16 years) with urolithiasis were treated between 1966 and 1979. There were 36 females (53%) and 32 males (47%). Sixteen children (24%) had associated urinary tract infection; 4 out of these (6%) presented with urinary tract malformation. Fifty-five calculi (89%) were found in the upper urinary tract (kidney and ureter); 24 of the chemically studied calculi (80%) were made of calcium salts. In 30 children, metabolic investigations were carried out, leading to the discovery of hypercalciuria in 17 (57%). In one patient, important vesico-ureteral reflux associated with urolithiasis led to renal failure.

Psychosocial and psychosomatic diagnoses in primary care of children.

In this study in seven primary care facilities the proportion of children recognized as having behavioral, educational, or social problems was much higher than generally assumed. Although there was great variability among the facilities, at least 5% and as many as 15% of children seen in one year were diagnosed as having these problems in all but the hospital teaching facilities. The prevalence was even higher among children from poor families. The variability among facilities was much less for psychosomatic problems, which were diagnosed in 8% to 10% of the children. For both psychosocial and psychosomatic types of problems, but especially for psychosocial ones, the proportion of visits with the diagnoses was much lower than the proportion of children with them, so that these problems engendered fewer visits for their management than might have been expected from their frequency in the population. However, available evidence suggests that individuals with unresolved psychosocial problems make more than their share of visits for other diagnoses. The findings of this study have implications for the content of educational programs for primary care practitioners, for the organization of primary care practice, and for the current debate over policy concerning reimbursement and benefit packages.