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The AT.LANTUS trial recently demonstrated the efficacy and safety of insulin glargine initiation and maintenance using two different treatment algorithms in poorly controlled type 2 diabetes mellitus (T2DM). This sub-analysis investigated glycemic control and safety in 686 patients switching from premixed insulin (premix) with or without (+/-OADs) to once-daily glargine (+/-OADs/prandial insulin). A 24-week, multinational (n=59), multicenter (n=611), randomized study comparing two algorithms (Algorithm 1: clinic-driven titration; Algorithm 2: patient-driven titration) in four glargine+/-OADs treatment groups: alone, once- (OD), twice- (BD) or >twice- (>BD) daily prandial insulin. After switching to the glargine regimen, HbA(1c) levels significantly improved in the overall group (9.0+/-1.3 to 8.0+/-1.2%; p<0.001) and in all subgroups; fasting blood glucose levels also improved in all subgroups (overall: 167.1+/-50.0 to 106.9+/-27.2 mg/dL [9.3+/-2.8 to 5.9+/-1.5 mmol/L]; p<0.001). The incidence of severe hypoglycemia was also low in all four subgroups (< or =1.7%). Patients with T2DM switching from premix+/-OADs to glargine+/-OADs had significant reductions in glycemic control with a low incidence of severe hypoglycemia. The addition of prandial (OD, BD or >BD) insulin was associated with further improvements in glycemic control. These data provide support for the stepwise introduction of prandial insulin to a more physiologic basal-bolus regimen, which is under investigation.

This study assessed the incidence of severe hypoglycaemia with two insulin glargine titration algorithms: Algorithm 1 (increments of at least 10%, but not exceeding 4U) versus Algorithm 2 (1-6U increments). In this multicenter (n=409), multinational (n=54), open-label, 24-week randomized trial in 2442 subjects with sub-optimally controlled Type 1 diabetes (T1DM), mean prior insulin therapy duration was 14.6+/-10.3 years. The incidence of severe hypoglycaemia was similar with Algorithms 1 and 2 (16.6events/100 patient-years versus 14.4events/100 patient-years). There were similar rates of both symptomatic and nocturnal hypoglycaemia. HbA(1c) and fasting blood glucose (FBG) decreased significantly (baseline to endpoint; p<0.001), and comparably with Algorithms 1 and 2 (HbA(1c): -0.64% versus -0.72%; FBG: -57mg/dL versus -59mg/dL). Mean basal insulin dose increased with both algorithms (+5.7U versus +5.9U). In a diverse population with longstanding T1DM, transfer from any insulin regimen, including basal-bolus or premixed insulin to an insulin glargine-based regimen resulted in significant improvements in glycaemic control, with low rates of severe hypoglycaemia, irrespective of the titration algorithm used.

Objective: This study investigated the effect of insulin glargine (LANTUS) versus NPH insulin on metabolic control and safety in Asian patients with Type 2 diabetes, inadequately controlled on oral hypoglycemic agents (OHAs)., Study Design and Methods: In this open-label, randomized, parallel, multinational, 24-week, non-inferiority study, 443 patients received either once-daily insulin glargine (n=220) or NPH insulin (n=223) at bedtime, plus glimepiride (Amaryl)., Results: Baseline characteristics were similar between the two groups. HbA(1c) levels decreased in the insulin glargine and NPH groups over the study period in the per-protocol (PP; -1.10% versus 0.92%) and full-analysis (FA; -0.99% versus -0.77%) populations. In the PP population, the difference between adjusted means (predefined equivalence region >-0.4%) was 0.19% (90% confidence interval [CI]: 0.02, 0.36), demonstrating non-inferiority between the two treatments. In a superiority analysis (FA population), the difference between adjusted mean changes in the two groups was 0.22% (95% CI: 0.02, 0.42), demonstrating the superiority of insulin glargine (p=0.0319). Moreover, the number of hypoglycemic episodes was significantly lower with insulin glargine versus NPH insulin (p<0.004), particularly severe (p<0.03) and nocturnal (p<0.001). Daily insulin dose increased from 9.6+/-1.5 to 32.1+/-17.6 U in the insulin glargine group and from 9.8+/-1.9 to 32.8+/-18.9 U in the NPH insulin group., Conclusion: These results confirm earlier reports that insulin glargine provides superior glycemic control with less hypoglycemia and demonstrates that these benefits are consistent between different ethnicities.

Background/aims: In patients with cirrhosis, decreased renal water excretion is a common complication. Niravoline (RU51599), a kappa-opioid receptor agonist, has been shown to induce an aquaretic response. The aim of this study was to evaluate the aquaretic effect and tolerance of niravoline in patients with cirrhosis., Methods: Biochemical tests and hemodynamic values were determined before and 1, 2, 3 and 24 h after niravoline administration at doses ranging from 0.5 to 2 mg iv in 18 patients with cirrhosis., Results: Diuresis significantly increased in the first hour from 64+/-9 to 146+/-31 ml/h, and returned to basal values after 3 h. Free water clearance also significantly increased, reaching the positive range at 1 h. Plasma osmolality significantly decreased at 2 h (from 290+/-4 to 286+/-4 mOsm/kg). Plasma sodium concentrations increased significantly at 3 h (from 133+/-1 to 134+/-1 mEq/l). Heart rate and arterial pressure did not change. The highest doses (1.5 mg or 2 mg) induced personality disorders and mild confusion within 2 h. These effects reversed completely within 8 h., Conclusion: This study shows that niravoline administration induces an aquaretic response and is well tolerated, at moderate doses, in patients with cirrhosis. Thus, moderate doses of niravoline may be useful for treating patients with cirrhosis and water retention.

We noninvasively investigated the effects of a single 30-min i.v. infusion of a 2-mg dose of niravoline, a new selective kappa-opioid agonist, on systemic and regional (brachial artery) hemodynamics, on plasma levels of the main hormones regulating the cardiovascular system, on diuresis and on plasma and urinary osmolalities and electrolytes. This was a placebo-controlled, randomized, double-blind, crossover study performed in 12 healthy volunteers. Compared with placebo, niravoline induced a significant, early and potent diuresis, which peaked within 2 hr (urine output increased 2.4-fold) and lasted for 4 hr. Niravoline significantly decreased, between 0 and 2 hr, urine osmolality (-71%) and sodium (-38%) and potassium (-29%) excretion and significantly increased plasma osmolality and natremia, without changing kalemia. Niravoline induced a slight, but significant, increase in blood pressure (+8% at 0.5 hr), which disappeared within 2 hr. Because heart rate, stroke volume and cardiac output were not modified, this effect was due to an increase in total peripheral resistance (+22% at 0.5 hr). Niravoline did not modify brachial artery diameter and flow and corresponding vascular resistance. Niravoline tended to decrease plasma vasopressin levels and urinary excretion and significantly increased plasma levels of norepinephrine (+44% at 0.5 hr), active renin (+22% at 1.25 hr), aldosterone (+52% at 1.25 hr) and atrial natriuretic factor (+20% at 2 hr). We conclude that niravoline induces a potent aquaretic effect associated with antinatriuresis and antikaliuresis. These main effects are accompanied by a stimulation of the sympathetic and reninangiotensin systems and a slight and transient increase in blood pressure.

Background: Syringomyelia is rare in children aged less than 10 years, and bladder dysfunction is an unlikely first manifestation. This report describes a case of repeated episodes of acute urinary retention in a young girl revealing syringomyelia and Arnold-Chiari malformation., Case Report: A 2.5 year-old girl was admitted because she was suffering from acute urinary retention. Her poor appetite had been treated with cyproheptadine, a histamine type I blocking drug. Clinical investigation revealed no local cause for this bladder dysfunction except moderate spasticity of the legs. Cystography showed no vesicoureteral reflux. Because the episodes of urinary retention recurred each day, magnetic resonance imaging (MRI) was performed; this showed the typical features of syringomyelia extending from C5 to T11 plus Arnold-Chiari malformation. The cyproheptadine was discontinued and the urinary retention disappeared., Conclusion: Cyproheptadine may have revealed latent neurogenic bladder in this case, although urodynamic studies, performed 3 months later, detected no bladder dysfunction.

Background: Primary hyperparathyroidism is rare in children and adolescents. Bone changes may produce pain in the back or extremities, but this is rarely the first symptom of the disease., Case Report: A 13 year-old girl suffered from pain in the back and lower extremities. Progressive bilateral genu valgum appeared. One year later, she became lame because of the deformity. ECG showed cardiac arrhythmia with atrial extra systoles. The serum calcium concentrations were 3.36 and 3.8 mmol/l, phosphate 0.76 mmol/l and alkaline phosphatases 6,612 U/I (N: 90-300). Urinary excretion of calcium was 17 and 26 mg/kg/day and the renal tubular reabsorption of phosphate was 77%. Radiological studies revealed resorption of subperiosteal bone, best seen along the margins of the phalanges, demineralization of the skull vault, bilateral coxa vara and zones of calcification on knee metaphyses. The serum concentration of parathyroid hormone (PTH) was 1,066 pg/ml (N: 10-55) and that of 1-25(OH)2D3 was 125 ng/ml (N: 20-80). Ultrasonography showed a heterogeneous mass, 23 x 15 mm, suggesting a parathyroid adenoma. This adenoma was independent of the left inferior parathyroid. It was removed and the biochemical findings gradually returned to normal. Bone demineralization also disappeared and the knee deformities were surgically corrected 9 months later., Conclusions: Bone changes may occasionally cause severe pain, indicating demineralization and hypercalcemia: hyperparathyroidism is one cause of such changes.

Background: The production of recombinant erythropoietin, has made large quantities of pure protein available for clinical studies. Published reports have concentrated on patients with end-stage renal disease, who develop transfusion-dependent anemia., Material and Methods: A total of 58 children aged less than 18 years (mean age: 11.48 +/- 4.62 years) with end-stage renal disease (hereditary in 9, congenital in 21 and acquired in 28) treated between July 1987 and February 1990, were included in the study. The mean duration of dialysis (hemodialysis in 56, peritoneal dialysis in 2) at the onset of the study was 35 +/- 28 months. 3 children had undergone bilateral nephrectomy, and 2 were infected with HIV. 54 children were given a phosphate-binder, 10 were given iron and 20 were given folic acid supplements. During the 6 months preceding the study, 51 patients received at least one blood transfusion (40 received 1 to 4 and 11 received 5 to 9 transfusions of packed red blood cells). Recombinant human erythropoietin (rHu EPO) (40 units/kg) was given intravenously three times per week for at least 6 weeks, with the exception of the first 9 patients who were given 80-100 units/kg. When the hematocrit increased less than 0.5% per week (or 3% for 6 weeks), the dose of rHu EPO was increased in stages, without exceeding 200 units/kg/injection. When the hematocrit reached 30 to 35%, the dose of rHu EPO was decreased by half, then gradually adjusted to maintain the hematocrit within this range., Results: The mean value of reticulocytosis increased from 4.88 to 10.58% and the hematocrit increased from 19.34 to 29.95% during the study. The patients also reported that their appetites and general condition improved. The need for transfusion dramatically decreased after the first month of treatment. The main adverse effect of the rHu EPO administration was an increase in the number of patients with hypertension (31/45 versus 19/45), indicating the need for good control of blood pressure before treatment., Conclusion: Erythropoietin treatment increases packed blood volume in a dose-dependent fashion. Most patients need no further transfusion and the quality of life clearly improves.

The authors report the case of a 33 month-old child who presented some of the classical symptoms of the Henoch-Schoenlein purpura - arthritis, purpuric lesions of the lower extremities - associated with the full-blown picture of a post-infectious glomerulonephritis - low level of C3, proliferation of mesangial cells, exudation with large number of leukocytes, and C3 glomerular deposits. These findings and others previously described suggest that the Henoch-Schoenlein purpura is a syndrome and that some of its manifestations may occur in patients with post-infectious glomerulonephritis.

The Hickman catheter is a single or double lumen catheter made of a silicone polymer; it is introduced surgically into the superior vena cava or the right atrium. The authors have used this catheter in 11 children, aged from 3 to 15 years and weighing from 10 to 40 kg, either for haemodialysis in children without arteriovenous fistula (n = 10), or for plasma exchanges (n = 1). In 5 of the 10 children, an arteriovenous fistula was created while the catheter was being installed. The catheter was left in place for a mean period of 48 days and a maximum period of 5 months. Data from the literature suggests that this instrument can be used for even longer periods. Dialysis was satisfactory in 8 out of 10 cases. No infection or thrombosis of the catheter was observed. The catheter was not perfused between haemodialysis sessions or blood exchanges.

The Senior and Loken's syndrome is a condition associating nephronophtisis and tapetoretinal degeneration. The case reported had a quite unusual transmission: isolated ophthalmologic impairment in the father, isolated renal impairment in the son. Thus, the genetic transmission of this syndrome is probably not univocal.

A 7 year old boy presented with a history of recurrent episodes of sinusitis and otitis. He developed paresis of the external muscle of his right eye with exophthalmos. A biopsy of his sinus mucosa demonstrated necrotizing granulomatous involvement of the membranes with the presence of multiple giant cells interspersed in zones of fibrosis. A diagnosis of Wegener's granulomatosis was entertained. However the absence of pulmonary and renal manifestations did not allow for a definitive diagnosis to be made. He later developed hematuria and a renal biopsy demonstrated a renal lesions consistent with Wegener's granulomatosis. He has responded well to Cyclophosphamide and Prednisone therapy.

Post-transplant polycythemia is not uncommon in adult patients and is usually transient, responding to phlebotomy. Five pediatric patients developed erythrocytosis post-transplantation. Three patients had end-stage renal disease due to cystinosis, one had reflux glomerulopathy and one had focal glomerular sclerosis. The probable causes of the polycythemia were graft arterial stenosis in three patients. In one, polycythemia occurred with nephrosis. Polycythemia with hypertension may indicate the presence of arterial stenosis in children post-transplantation.

Two children presented with nephrotic syndrome. Renal biopsy demonstrated minimal lesion nephrosis with mesangial IgA deposits. Response to prednisone therapy was prompt in both cases. The clinical and histologic features of these and other reported cases suggested a diagnosis of minimal lesion nephrosis and not IgA nephropathy (Berger's disease).

We report the cases of 2 children in whom, during active nephrotic syndrome, simultaneous dilutional hyponatremia and increased hematocrit were observed. Fluid and electrolyte disorders rapidly became normal after albumin infusion, sodium and water restriction and diuretic administration. Increased hematocrit level, which reflects the decreased intravascular compartment, is observed rarely in the course of nephrotic syndrome and should not lead to administering water and salt. The mechanisms which control the salt-water balance in the course of the nephrotic syndrome remain unclear.

Four patients with total aganglionosis of the intestine had renal abnormalities. Two patients had cortical subcapsular cysts, one had unilateral renal agenesis and one other had unilateral renal dysplasia. The consistency of renal anomalies with total aganglionosis suggests the presence of a common genetic origin.

A boy, aged 14 1/2 years, presented with Burkitt leukemia. His renal status was normal before treatment. Chemotherapy (SFOP LMB 86 protocol) was begun Oct. 9, 1986. After the first 2 courses of chemotherapy, the patient had Gram negative sepsis treated with cefotaxime, netilmycine, Vancomycin and ornidazole. During sepsis, nephrotic syndrome developed (albumin 25 g/l, non selective proteinuria 15 g/24 h), with moderately high blood pressure, functional renal failure (creatinine 141 mumols/l, U/P urea = 20), polyuria and tubular damage. Kidney ultrasonography was normal. Needle biopsy showed minimal glomerular lesions, acute tubular lesions, and no deposits in immunofluorescence. The nephrotic syndrome disappeared within 3 weeks, with treatment of leukemia. He is at present in complete remission with a follow-up of 25 months.

Changes in serum protein and albumin levels following resolution of proteinuria were studied in 67 children with nephrosis. These two parameters returned to normal only after the 21st day, i.e. well after the natriuretic crisis and resolution of edema. Our results are consistent with recent studies showing that the fluid and electrolyte changes seen in the urine at resolution of the proteinuria (increased diuresis and natriuresis) are not due to a return to normal of serum protein and albumin levels. They probably reflect correction of an intrarenal abnormality whose mechanism is unclear.

In the most common clinical expression of infantile polycystic disease, the kidneys are greatly enlarged in the neonatal period. When the child gets older the kidneys become smaller. In this case report, both kidneys kept growing after birth causing abdominal distention and respiratory distress. The differential diagnosis was a bilateral massive nephroblastomatosis, but the renal pathology showed characteristic features of infantile polycystic disease.

The long-term damaging potential of remnant nephron hyperperfusion was investigated in patients who had undergone unilateral nephrectomy in childhood. 27 such patients were examined after a mean of 23.3 years postnephrectomy. The average creatinine clearance was 83.9 +/- 16.5 ml/min/1.73 m2 or 74.3% of that in healthy controls with two kidneys; it was a value similar to that reported 3 to 6 months postnephrectomy in kidney donors. Age at the time of nephrectomy, duration of follow-up, or sex had no influence on the residual creatinine clearance. None of these patients had clinically important hypertension or proteinuria. Since so little evidence of kidney damage could be documented after such a long observation period, hyperperfusion would seem to be seldom of clinical importance in man unless other factors were present.