[Rheumatic joint disease in childhood and adolescence ]. / Rheumatische Gelenkerkrankungen im Kindes- und Jugendalter.

Rheumatic joint disease in childhood and adolescence is relatively rare. In the general population, 1 child with juvenile arthritis accounts for 100 adult patients with rheumatoid arthritis. At disease onset 50% of affected children are between 2 and 6 years of age. Symptoms are often subtle and pain is usually not the leading symptom. Early treatment of juvenile arthritis is essential in order to prevent long-term sequelae in affected children. Many children are introduced to a pediatric rheumatologist only with considerable delay. Therapy is based on NSAIDs, intra-articular steroid injections, and immunosuppressive drugs. In severe cases patients are treated with biologics. Physical and occupational therapy are important supportive measures in the treatment.

[Rheumatic joint disease in childhood and adolescence]. / Rheumatische Gelenkerkrankungen im Kindes- und Jugendalter.

Rheumatic joint disease in childhood and adolescence is relatively rare. In the general population, 1 child with juvenile arthritis accounts for 100 adult patients with rheumatoid arthritis. At disease onset 50% of affected children are between 2 and 6 years of age. Symptoms are often subtle and pain is usually not the leading symptom. Early treatment of juvenile arthritis is essential in order to prevent long-term sequelae in affected children. Many children are introduced to a pediatric rheumatologist only with considerable delay. Therapy is based on NSAIDs, intra-articular steroid injections, and immunosuppressive drugs. In severe cases patients are treated with biologics. Physical and occupational therapy are important supportive measures in the treatment.

Impact of uraemia on food efficiency and the pulsatile mode of growth hormone secretion in rats.

In view of the profound growth failure resulting from renal insufficiency and uraemia, the present studies were designed to specifically investigate food efficiency and the pattern of GH secretion under these conditions. Animals were made uraemic by 5/6 nephrectomy (Nx) and feeding a high-protein diet. Three groups of animals were studied: uraemic (Ur); sham-operated, fed ad libitum (Sh); and sham-operated pair-fed with the uraemics (PF). Food intake per 100 g body weight and food efficiency (g weight gained per g food consumed) were calculated. Fourteen days after 5/6 Nx, blood samples were taken via intra-atrial catheters at 10-min intervals over a period of 6 h. GH was measured in plasma by radioimmunoassay. GH pulsatility was analysed by multiple parameter deconvolution. The growth rate of Ur animals was significantly lower than that of Sh. The body weights of the Ur animals were also lower than PF due to an initial period of weight loss. Both Sh and PF animals showed the typical negative slope of food intake as body weight increased. In contrast, the Ur animals showed a positive slope of food intake. The lower rate of growth and the elevated food intake corresponded to a decreased food efficiency for the Ur group. Deconvolution analysis of pulsatile GH release demonstrated a significant increase in GH half-life in the Ur animals. The amplitude and mass of GH secretory pulses were decreased, whereas the number of detectable secretory bursts was increased. These changes were specific to uraemia with respect to half-life and number of pulses.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of the synthetic glucocorticoid, deflazacort, on body growth, pulsatile secretion of GH and thymolysis in the rat.

DESIGN: Deflazacort (DFZ) is a relatively new glucocorticoid that has been reported to exhibit fewer side-effects than other commonly used corticosteroids. The present study was designed to test the effects of DFZ on thymus gland involution (thymolysis), as compared with body growth and the secretory pattern of GH in the rat. Beginning at 38 days of age, male animals were treated for 8 consecutive days by s.c. injection of DFZ (0.15mg/day), cortisone (CORT) (5mg/day) or vehicle (control, CTRL). RESULTS: Both glucocorticoids had a similar thymolytic effect and caused growth failure, but the growth rate for the DFZ group was significantly higher than that of the CORT group. On day 46, pulsatile GH secretion was quantitated by blood sampling via an indwelling catheter at 10 min intervals for 6h. GH was assayed by RIA and analyzed by multiparameter deconvolution. CORT caused an increase in pulse frequency (5.8+/-0.4 (s.e.m.)) in comparison to DFZ (4.4+/-0. 4) and CTRL (3.8+/-0.3). Both glucocorticoids significantly shortened the interval between secretory bursts. In CTRL animals the interval between bursts was 69.3+/-4.5 min. In DFZ animals this was reduced to 58.5+/-7.1 min, and in CORT rats it was further reduced to 47.0+/-2.6 min. The mass of GH secreted per burst was reduced in CORT animals (52% of CTRL), while DFZ did not alter this parameter. A similar trend was observed for total GH production, with CORT causing a reduction and DFZ not affecting the secretion. CONCLUSION: Rats treated with glucocorticoid show a profound thymolytic effect, as well as important changes in growth. While CORT suppresses GH secretion and alters its pulsatile mode of release, DFZ causes a less significant alteration in the pattern of GH secretion and does not negatively affect the overall amount of GH secreted.

Effects of deflazacort and cortisone on body growth, thymus weight and gene expression of growth-related proteins in the rat.

Deflazacort is an oxazoline derivative of cortisone with presumably less serious side effects, but its effects on growth factors are unknown. The present experiments in Long Evans rats were carried out to investigate how deflazacort administration affected the growing rat, especially in relation to hepatic insulin-like growth factor I (IGF-I) and growth hormone receptor (GHR) messenger ribonucleic acid (mRNA). Four groups of animals were used: those treated with cortisone, with two different doses of deflazacort and with vehicle. Subcutaneous injections were given daily for 8 days. Thymus weight was reduced in all treated groups, with a comparable magnitude of reduction in the groups treated with cortisone and the higher dose of deflazacort (DF1). Daily weight gain was reduced significantly after cortisone treatment, but less so in the DF1 rats. Liver IFG-I and GHR mRNA were lower in the cortisone and deflazacort than in controls. However, GHR mRNA was reduced significantly only by cortisone and not by DF1. We conclude that growth failure is less severe in the DF1 rats compared to cortisone rats, which corresponds to the reduction in hepatic GHR mRNA.

Growth hormone and insulin-like growth factor in non-uremic acidosis and uremic acidosis.

Growth retardation is a cardinal feature of children with renal tubular acidosis. This is reversible by correcting the non-uremic acidosis with alkali therapy. Sodium bicarbonate solutions or citrate solutions have been used for this purpose. However, the odious taste of these medications almost invariably causes medical noncompliance. The persistent and often profound metabolic acidosis from medical noncompliance, precipitates hypercalciuria and hypocitraturia, and increases the risk of nephrocalcinosis. The mechanism of the growth retardation in renal tubular acidosis is thought to be related to a blunting of anterior pituitary growth hormone secretion. In experimental metabolic acidosis, the growth hormone secretory pulse areas are reduced. Just as importantly, hepatic growth hormone receptor expression and IGF-I mRNA were blunted in metabolic acidosis. In uremia, growth retardation is secondary to a host of factors including metabolic acidosis, renal osteodystrophy, and the side effects of treatment such as corticosteroids, which compound the growth retardation. Growth hormone secretion by individual pituitary cells was stimulated by corticosteroids but, paradoxically, the total number of somatotropes was suppressed. In uremia, the secretion of growth hormone was not different from controls at any level of growth-hormone-releasing hormone challenges. Hepatic IGF-I mRNA was markedly reduced in uremic rats. Growth hormone receptor expression was significantly reduced in uremic acidotic rats. The growth hormone and IGF-I expression on the growth plate of the long bone of uremic rats was reduced. IGF-I immunoreactivity was present in both the hypertrophic and proliferative zones. The lack of growth of the proliferative zones suggested growth hormone and IGF-I resistance in uremic chondrocytes.

Anti-proliferative effects of deflazacort on Nb2 cells as quantitated by formazan production.

Prolactin and other lactogenic hormones are mitogenic for the rat T-cell lymphoma line, Nb2. Glucocorticoids have antiproliferative effects on these cells. A limiting feature of experiments utilizing the Nb2 line is their labor-intensive nature. We therefore adapted the commonly used MTT dye proliferation assay for the Nb2 cell line. While rPRL, hPRL, oPRL, hGH, bPL, and to a lesser extent bPRL stimulated the Nb2 cells, hormones without lactogenic activity, rGH and oGH did not. Human serum and rat sera from animals bearing a PRL-secreting tumor stimulated the Nb2 cells in parallel to standards. Glucocorticoids had anti-proliferative effects on Nb2 cells in the presence of half-maximal or maximal PRL doses, as measured by the MTT proliferation assay. It has been claimed that an oxazoline steroid, deflazacort, has anti-inflammatory effects in clinical studies with fewer of the deleterious side-effects common to glucocorticoids. We therefore compared the in vitro anti-proliferative effects of deflazacort with other glucocorticoids. Deflazacort's negative effect on Nb2 cell proliferation was similar to that of cortisol and prednisolone and less than that of dexamethasone. We conclude that the MTT proliferation assay can be used to study both mitogenic and anti-proliferative substances in Nb2 cells. In addition we found that deflazacort acts similarly in vitro to other glucocorticoids.

Perturbations in potassium balance.

Hyperkalemia and hypokalemia are commonly encountered in medical practice. Differential diagnosis and therapeutic approaches have been presented to provide an informed choice for the practicing physician.

Continuous peritoneal dialysis in children.

During the period from June 1985 to December 1991, 48 children were treated with continuous peritoneal dialysis (CPD) in our centre because of acute renal failure. The median age was 1.8 years (range 0.01-17.1). The most common diagnoses were: hemolytic uremic syndrome (n = 22), anuria after cardiac surgery (n = 7), and septicemia with multiorgan failure (n = 7). Kidney function recovered in 35 (73%); 13 (27%) died of their original disease. One further patient with HUS recovered from dialysis but died of cerebral complications shortly afterwards. One patient remained anuric and requires renal replacement therapy. Hyperkalemia, when present initially, and uremia could be controlled adequately in all cases. However, ultrafiltration posed problems when cardiac output was low. Peritonitis occurred in 11 patients; in 8 children the Tenckhoff catheter had to be revised because of leakage (5), flow problems (2), or bowel perforation (1). CPD proved to be an excellent method to treat acute renal failure in children of all age groups. The rate of complications was acceptable.

Implementation of a program model to develop specialty staff resource nurses in genetics.

A CNS program to develop staff resource nurses in the specialty area of genetics was implemented. The purpose of the program was to provide staff nurses with necessary knowledge and skills to improve identification of and services for clients with genetic conditions. Twenty-eight staff nurses completed the program, which consisted of a 2-day workshop, a 3-month preceptorship, and regularly scheduled continuing education meetings. Pre- and postworkshop test scores indicated a significant gain in nurses' knowledge of genetic concepts and resources. Resource nurses' interventions with genetic clients increased 3 and 6 months after the workshop. Staff nurse-to-CNS referral of genetic clients continued to increase 3 and 6 months after the workshop. The described program can be used as a model by CNSs in other settings and specialty areas.

Clearance and removal of oxalate in children on intensified dialysis for primary hyperoxaluria type 1.

Patients with end-stage renal failure owing to primary hyperoxaluria type 1 (PH1) receive dialysis while waiting for transplantation. So far, dialysis has not been shown to overcome the problem of ongoing oxalate production and deposition at extrarenal sites. We report on six children with PH1 who had to be dialyzed for a median period of 2.5 years while awaiting liver transplantation. Aiming at preventing oxalate tissue accretion, oxalate mass transfer was studied and dialysis intensified accordingly. Mean plasma oxalate concentration was between 51 and 137 micromol/l. In three of the six patients with a urinary output between 630 and 3140 ml, urinary removal of oxalate was between 5.6 and 12.4 mmol/week/1.73 m2. Hemodialysis (HD) in five of the six patients demonstrated a mean oxalate dialysance between 158 and 444 l/week/1.73 m2. Peritoneal dialysis (PD) in two of the six patients showed mean oxalate clearances of 66 and 103 l/week/1.73 m2. One patient received HD and PD. By adding all modes of elimination, a mean total oxalate mass between 10.1 and 24.1 mmol/week/1.73 m2 was removed. Dialysis is still necessary as a temporary therapy for a number of patients with PH1. Dialysis should be instituted pre-emptively and maximally exploited by intensified HD/PD treatment protocols, without, however, cutting back urinary output.

Anuria during pneumoperitoneum in infants and children: a prospective study.

INTRODUCTION: Transient oliguria during laparoscopic surgery is a known phenomenon. Currently, no data on the impact of pneumoperitoneum on renal function in children are available. PATIENTS AND METHODS: Thirty children with normal kidney function, who underwent laparoscopic surgery, were included in a prospective study. A transurethral catheter was placed to measure urine output during and 6 hours after operation. Renal blood flow (resistive index) was evaluated by Doppler ultrasound of a segmental renal artery before surgery, every 15 minutes during laparoscopy, and after 24 hours. Blood and urine samples were studied before and 24 hours after surgery. Hemodynamic parameters were monitored continuously during standardized anesthesia, including a standardized intravenous infusion regimen. RESULTS: Urine output decreased within 45 minutes of pneumoperitoneum in all patients. Of 8 children younger than 1 year, 7 (88%) developed anuria vs 3 of 22 (14%) children aged 1 to 15 years (P < .001). Nine children 1 year and older (32%) developed oliguria. There was a significant recovering in the mean urine output until 5 to 6 hours after pneumoperitoneum in both age groups. No significant alterations of the renal blood flow (resistive index) and the serum and urine levels of cystatin C, creatinine, and urea nitrogen were evident until 24 hours postoperatively. The volume of infusion during pneumoperitoneum did not correlate with urine output. CONCLUSION: Pneumoperitoneum leads to anuria in most children younger than 1 year and to oliguria in about one third of older children. This is a completely reversible phenomenon. Urine output should not be taken into consideration for calculating intravenous fluid administration during pneumoperitoneum in children.

Primary hyperoxaluria type I.

Primary hyperoxaluria type I is a metabolic disorder caused by the deficiency of the peroxisomal alanine:glyoxylate aminotransferase. The disease is inherited as an autosomal recessive trait. The clinical course is outlined based on data from 330 published cases. Diagnostic cornerstones are clinical parameters, urinary excretion of oxalate and glycolate, and the determination of enzyme activity in liver tissue. Principles of conservative treatment, e.g. volume load and pyridoxine substitution, are described as well as experience with different modes of dialysis and transplantation. Kidney transplantation is associated with a high rate of recurrence of the original disease despite excellent management resulting in many instances in early graft loss. Liver transplantation offers the possibility to correct the metabolic defect and to prevent the progression of crystal deposition in the body.

The purification and properties of human lens glutathione reductase.

A very simple and rapid method for the purification of human lens glutathione reductase has been developed. The method involves only two steps--affinity chromatography on 2',5'-ADP-Sepharose 4B and gel filtration on Sephacryl S-200. With whole lenses, the purification achieved is over 18000-fold and 80% of the activity in the tissue homogenate is recovered as an enzyme with a specific activity of 218 IU/mg-1. Glutathione reductase was purified from the nucleus and cortex of type I cataractous human lenses and the properties of the two enzymes were compared. No differences could be detected between these enzymes in their specific activities, molecular weights, pH-activity profiles, heat labilities, reactivity towards various substrates and kinetic parameters (Vmax and Km) for glutathione, NADPH2 and NADH2. Therefore, it was concluded that specific alterations in the properties of nuclear glutathione reductase were not responsible for the decreased ability of the lens nucleus to protect itself against oxidative insults. Several different glutathione reductase preparations were examined for their ability to cleave mixed disulphides of lens proteins and glutathione. Only crude tissue extracts (wheat germ and whole lens) were able to cleave the mixed disulphides: no activity was observed with purified lens or yeast glutathione reductases. Therefore, it was concluded that glutathione reductase does not cleave mixed disulphides.

Writing Amish culture into genes: biological reductionism in a study of manic depression.

Critical realism is used to explore the problem of reductionism in a classic (the Amish Study) and widely-cited study of manic depression. Along with related ideas drawn from the works of R.C. Lewontin, Arthur Kleinman, and Byron Good, it is shown that natural and social scientists deploy atomistic and holistic reductionism; this, in turn, leads to the construction of artificially 'closed systems' through the control of variables or exogenous forces. The psychiatric genetic studies of the Amish were predicated on the assumption that Amish society is homogeneous and unchanging and, therefore, closed. We conclude by arguing that interactions between behaviors and genes, where they exist, take place only within open systems, characterized by multiple mechanisms-social and biological-that together co-determine any event. To move forward, it is argued, behavior and gene research requires recognition and resolution of the philosophical conundrums that accompany reductionism.