Hemothorax under thrombolytic therapy with recombinant tissue

We present the case of a 16-year-old girl with an extended thrombosis of the femoral and iliac vein and the inferior vena cava during pleuropneumonia; predisposing risk factors for thrombophilia were: use of contraceptives, nicotine abuse and congenital deficiency of antithrombin III (not previously diagnosed). Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA; initial dose: 0.08 mg/kg/h) was started. 2 days later - after diagnosis of an extended hemothorax: 1500 ml blood were obtained after thoracocentesis, transfusion of packed red blood cells was necessary - rt-PA was stopped, with only heparin (400 U/kg/d) being administered. 36 h later - the thrombosis had not yet changed - the thrombolytic therapy with rt-PA was continued in a markedly reduced dose (0.015 mg/kg/d) with no further bleeding complications. 8 days later - after successful thrombolysis - rt-PA was stopped, heparin was given for another 10 days, then cumarin was administered orally.     

Thrombolysis with rt-PA in children with arterial and venous thromboses--a new therapy concept

Thrombolytic therapy usually used for thrombosis in the adult has been administered as a therapeutic regiment in pediatric patients (parental consent was sought prior to the treatment with rt-PA). We report our experience with rt-PA in 17 children and adolescents suffering from arterial (n = 4) or venous thrombosis (n = 13) due to local rhabdomyosarcoma, acute lymphoblastic leukemia, chronic myeloblastosis, sickle cell anaemia, parenteral nutrition, haemolytic uremic syndrome, central arterial and venous catheters and septicemia Thrombotic diseases have been diagnosed by Doppler ultrasound, computed tomography, angiography and phlebography. Rt-PA therapy was started immediately after diagnostic procedures had been performed. Rt-PA dose varied from 0.2 mg as a single dose to 0.8 mg/kg bw/d over a three day period in children local thrombolysis was performed. In patients requiring systemic thrombolytic therapy rt-PA was administered from 0.8 mg/kg bw/d in three days to 2.0 mg/kg bw/d over a whole period of three weeks in both groups during thrombolysis low dose heparin was added. When rt-PA infusion was terminated heparin (70 IU - 400 IU/kg bw/d) was administered for 7 to 14 days in order to prevent reocclusion. Later prophylaxis with coumarin derivatives in venous thrombosis and antiplatelet agents in arterial occlusive diseases was performed. In no patient did we see a decrease of fibrinogen and plasminogen during rt-PA therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early intracardiac thrombosis in preterm infants and thrombolysis with recombinant tissue type plasminogen activator.

OBJECTIVES: To determine the incidence of catheter related thrombosis and to test the efficacy of recombinant tissue type plasminogen activator (rt-PA) in preterm infants. STUDY DESIGN: From January 1995 to December 1998, echocardiography was performed in the first few days of life in 76 very low birthweight (< or = 1500 g) infants out of a total of 147 having an umbilical catheter placed. When intracardiac thrombosis was diagnosed, rt-PA infusion was performed. RESULTS: Four infants (5%) developed an intracardiac thrombosis during the first few days of life. In three of them, rt-PA at a dose of 0.4-0.5 mg/kg in a 20-30 minute bolus led to dissolution of the clot. One patient received a three hour infusion after the bolus, at a dose of 0.1 mg/kg/h, with resolution of the thrombus. No systemic effects were observed after rt-PA infusion. CONCLUSIONS: Early thrombosis may occur as a complication of umbilical catheterisation in preterm infants; early echocardiographic detection of this disorder allows complete, safe, and rapid lysis with rt-PA.     

Successful lysis of a septic thrombosis of the superior vena cava using recombinant tissue-plasminogen activator

Recombinant human tissue-type plasminogen activator (rt-PA) was successfully given via central vein to a 1.7 year old child with angiographically documented septic vena cava superior thrombosis Thrombolytic therapy with rt-PA was started with 0.2 mg/kg as a slow bolus injection followed by an infusion of 0.8 mg/kg over 60 min. rt-PA was applicated 12 hours after an urokinase bolus in a dosage of 8000 E/kg and heparin infusion of 500 E/kg/die. No clinical side effects or alterations in the plasmatic coagulation profile were noted. The prompt clinical response suggests that the use of rt-PA in thrombotic disease should be investigated further to establish efficacy, dosing guidelines, complication rates, and contraindications in childhood.     

肾病综合征并发颅内静脉窦血栓五例

目的 探讨肾病综合征患儿并发颅内静脉窦血栓的诊断,及应用尿激酶与低分子肝素等联合治疗效果.方法 采用尿激酶与低分子肝素等联合治疗.(1)尿激酶:初剂量2000～4000 U/(kg·d),首剂冲击量20 000～40 000 U在15～30 min内滴完,而后将余量用输液泵均匀地泵入,第2天起2000 U/(kg·d)用输液泵均匀地泵入,1个疗程3～7 d.治疗期间每周测定3次凝血酶时间(TT)、激活的部分凝血致活酶时间(APTT),应控制TT和APTT应小于2倍延长的范围内,特别注意有无出血情况.(2)低分子肝素:每次100～120 AXaIU/kg,每天1～2次,腹部皮下注射,2周1疗程.(3)抗血小板凝聚药物:长期口服双嘧达莫3～5 mg/(kg·d),每天2～3次,疗程3个月.结果 5例肾病综合征并发颅内静脉窦血栓,经过尿激酶、低分子肝素与双嘧达莫等联合治疗,1个月后患儿临床症状均消失;复查血浆黏度1个月恢复正常,部分凝血活酶时间、血浆凝血酶原时间、纤维蛋白原降解产物1～2个月后恢复至正常,头颅CT或MRI检查1～3个月后静脉血栓消失,示颅内静脉窦血栓完全再通;随访无复发病例.结论 早期应用尿激酶抗纤溶、低分子肝紊抗凝及抗血小板凝聚药物综合治疗,其溶栓疗效较好.对儿童肾病综合征并发颅内静脉窦血栓的早期诊断与防治具有一定的推广价值.     

Thrombotic occlusion of the abdominal aorta in the neonatal period--successful thrombolytic treatment]

Aortic thrombosis during neonatal period is rare and usually related to an umbilical artery catheter. In an infant (birth weight 3110 gm) with complete thrombosis of the abdominal aorta distal to the renal arteries of unknown etiology we started a fibrinolytic therapy with streptokinase at the age of 12 days (streptokinase intravenously with an initial loading dose of 3000 U/kg, maintenance 1000 U/kg/hr for 2 days). This was followed by a heparinisation (10,000 U/m2/d, 24 hours later 200 U/kg/d). 72 hours after onset of therapy there was no blood pressure difference between upper and lower limbs. Side-effects of therapy did not occur; the success of medical treatment continued after termination of the heparinisation.     

Low-molecular-weight heparin in thrombotic disease in children and adolescents

PURPOSE: The use of unfractionated heparin (UFH) in children is problematic. In adults, subcutaneous low-molecular-weight heparin (LMWH) is as effective as UFH in the treatment of thrombosis. Because pediatric data are limited, the authors studied the use of enoxaparin in children. PATIENTS AND METHODS: Nineteen children (ages 18 days to 19 years; median age, 40 months) with indications for thrombosis treatment or prophylaxis were studied. Six patients (median age, 33 months), treated on a protocol that included pharmacokinetic studies, initially received enoxaparin 1 mg/kg subcutaneously every 12 hours; doses then were adjusted until target plasma levels of 0.5 to 1.2 anti-Xa U/mL were achieved. The records of 13 additional patients treated with enoxaparin off study were reviewed. RESULTS: In the first six patients, enoxaparin pharmacokinetics was found to be similar to that in adults; once targeted levels were achieved, these remained stable. Among all 19 subjects, 14 had treatment of active thrombosis and 5 underwent thrombosis prophylaxis. For treatment of thrombosis, enoxaparin 1 mg/kg initially was administered subcutaneously every 12 hours. Target anti-Xa levels were achieved with 0.55 to 1.5 mg/kg every 12 hours (mean, 0.98 mg/kg; median, 1.0 mg/kg) in 1 to 7 days (median, 1 day). All patients in the treatment group had clinical improvement within 2 to 5 days, and 12 had follow-up radiological studies that confirmed this. For prophylaxis, enoxaparin was given at 1 mg/kg subcutaneously every 24 hours. No new thrombi were clinically evident in this group. There was no major bleeding with enoxaparin; one patient had transient mild mucosal oozing. CONCLUSION: In this limited population, enoxaparin seems to be a safe, effective, and convenient alternative to UFH in children and adolescents. The adult therapeutic target range of 0.5 to 1.2 anti-Xa U/mL is readily achievable with a starting dose of 1 mg/kg every 12 hours in most children. Initial close monitoring with plasma anti-Xa activity should be done and doses adjusted to achieve target range, particularly in neonates. In the population of this study, enoxaparin seems as effective as UFH in the period immediately thrombotic episode. These results should be confirmed in the ongoing randomized trial comparing LMWH with UFH in children.     

Successful partial lysis of a 4-level-thrombosis by rt-PA - case report

Thromboembolism of the vena cava, the venae iliaca communis, externa, femoralis, poplitea, and the fibular vein group of the left lower limb was diagnosed in a 13 year old girl. Several thrombogenic risk factors (APC-resistence, homocystinuria, contraception, smoking) were identified. Due to painful symptoms and for prevention of postthrombotic syndrome continuous systemic thrombolysis with rt-PA (0,5 mg/kg/d), in addition to heparine, was performed for 6 days. Diagnostic imaging at the end of therapy demonstrated complete and partial recanalization of the vena cava inferior, venae iliaca communis and externa. The distal veins of the leg remained occluded. After catheterization of the internal jugular vein and placement of a cava filter only mild pulmonary embolism occurred during systemic thrombolysis. No further complications were observed. All in all, therapy was tolerated well. Systemic thrombolysis with rt-PA in children and adolescents, although not established for regular treatment, is an effective therapeutic option in severe venous thrombosis.     

Treatment of superior vena cava syndrome with recombinant tissue plasminogen activator in a sickle cell patient undergoing bone marrow transplantation

Superior vena cava (SVC) syndrome is a well-recognized clinical entity seen with mediastinal malignancies and intraluminal venous thrombosis. The role of recombinant tissue plasminogen activator (rt-PA) in the resolution of SVC syndrome caused by thrombosis in the bone marrow transplant settings has not been described. The authors report a case of SVC syndrome with good clinical response in a 16-year-old female with sickle cell disease undergoing an allogeneic bone marrow transplant (BMT) from her HLA identical sibling. Shortly after her transplant, she was found to have significant facial edema and swelling above the neck. Concomitantly, her renal function deteriorated with progressive elevation of serum urea nitrogen and creatinine levels, requiring the use of continuous veno-venous hemofiltration. An upper extremity venogram showed complete SVC obstruction (type III) with apparent inferior reflux into the azygos system. rt-PA was started at a dose of (0.5 mg/kg/day) for 2 days. There was a dramatic resolution of her symptoms, including significant improvement in renal function with increase in urine output. A repeat venogram showed free flow from the distal tip of the central line consistent with a patent superior vena cava. There was no evidence of any bleeding manifestations with rt-PA. This report highlights the usefulness of rt-PA as a treatment modality for SVC syndrome in the BMT settings.     

TREATMENT OF SUPERIOR VENA CAVA SYNDROME WITH RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR IN A SICKLE CELL PATIENT UNDERGOING BONE MARROW TRANSPLANTATION

Superior vena cava (SVC) syndrome is a well-recognized clinical entity seen with mediastinal malignancies and intraluminal venous thrombosis. The role of recombinant tissue plasminogen activator (rt-PA) in the resolution of SVC syndrome caused by thrombosis in the bone marrow transplant settings has not been described. The authors report a case of SVC syndrome with good clinical response in a 16-year-old female with sickle cell disease undergoing an allogeneic bone marrow transplant (BMT) from her HLA identical sibling. Shortly after her transplant, she was found to have significant facial edema and swelling above the neck. Concomitantly, her renal function deteriorated with progressive elevation of serum urea nitrogen and creatinine levels, requiring the use of continuous veno-venous hemofiltration. An upper extremity venogram showed complete SVC obstruction (type III) with apparent inferior reflux into the azygos system. rt-PA was started at a dose of (0.5 mg/kg/day) for 2 days. There was a dramatic resolution of her symptoms, including significant improvement in renal function with increase in urine output. A repeat venogram showed free flow from the distal tip of the central line consistent with a patent superior vena cava. There was no evidence of any bleeding manifestations with rt-PA. This report highlights the usefulness of rt-PA as a treatment modality for SVC syndrome in the BMT settings.     

Low molecular weight heparin for neonatal thrombosis

The clinical course of a term neonate (birthweight 3.14 kg) who developed thrombosis of the left common and internal iliac veins on day 21 following recovery from Streptococcus mitis septicemia, with shock diagnosed on day 13, is reported. Subcutaneous low molecular weight heparin (LMWH) was commenced (1.5 mg/kg 12 hourly for 10 days) after 13 h of standard heparin infusion, due to difficulties in securing a peripheral venous access. The inflammation of the left leg was completely resolved by day 5 of LMWH therapy. Prothrombin time, activated prothrombin time and fibrinogen levels were within normal limits during LMWH therapy. Treatment-related side effects, such as thrombocytopenia and bleeding tendency were not noted. Doppler studies 6 weeks after discharge home on day 33 revealed complete resolution of the thrombus. Apart from septicaemia and shock, the presence of an indwelling central venous catheter and a history of untreated maternal diabetes were additional risk factors for thrombosis. Because it is as effective as standard heparin, LMWH may be a therapeutic option for thrombosis in high-risk neonates, particularly given its ease of administration by the subcutaneous route, predictable pharmacokinetics and reduced incidence of adverse effects such as bleeding complications.     

Cyclosporine monitoring in the early post-transplant period in pediatric liver transplant recipients

Monitoring of CsA blood levels two h post-dose (C2) has shown a higher correlation to drug exposure than monitoring of trough levels (C0) at least in adults, but initial doses and target blood levels of CsA have yet to be established in pediatric transplant patients. The objectives of the study were to describe the pharmacokinetics of CsA administered by NGT in the first days after transplantation and the dose of Sandimmun Neoral required to achieve minimum therapeutic range blood levels. This study included 20 pediatric liver transplant recipients (mean age of 3.2 yr) treated with CsA administered by NGT from day one post-transplant until they were able to ingest oral medication. The study was continued until one yr of post-transplant follow-up. Eight h pharmacokinetic profiles were performed on days one, three, and five post-transplant to determine the minimum dose required to achieve the therapeutic range. All children received an initial dose of 15 mg/kg/day of CsA by NGT. Mean CsA doses administered on days one, three, and five were 16.8, 29.5, and 36.5 mg/kg/day, respectively. Mean C0 levels of 119, 310, and 337 ng/mL and mean C2 levels of 213, 753, and 888 ng/mL were obtained. No correlation was found between C0 and C2 levels and the AUC(0-8 h). Intravenous administration of CsA was required in 55% of patients. The biopsy-confirmed acute rejection rate was 45%, with graft and patient survival rates of 95 and 100%, respectively. CONCLUSIONS: Poor absorption of CsA in small children requires a considerable increase in dose. CsA exposure cannot be estimated by single C0 or C2 determinations in the early post-transplant period.     

Use of tissue plasminogen activator (rt-PA) in young children with cancer and dysfunctional central venous catheters

PURPOSE: To determine the efficacy and safety of low, nonescalating dose tissue plasminogen activator (rt-PA) in restoring the patency of occluded central venous access devices (CVCs) in children with cancer who weigh less than 30 kg. PATIENTS AND METHODS: A single-center review of the use of rt-PA (0.5 mg indwelling for 30 minutes in the CVC) was conducted in 42 cancer patients with large bore central venous access devices implanted over a 2-year period. All patients weighed less than 30 kg. None had been previously treated with a thrombolytic agent. The efficacy for restoring function to CVCs was measured and correlated with patient age, weight and CVC lumen size. Propensity to rethrombose following an initial occlusion and treatment was also determined. RESULTS: Of 235 doses of rt-PA administered in a 2-year period, 55 doses administered to 42 patients met the eligibility criteria as outlined. Twenty-nine patients (69%) had function restored with a single dose; 8 patients (19%) required 2 doses, and 5 patients (12%) failed 2 doses; for an overall success rate of 88%. No significant adverse events occurred. Of the 37 cleared CVCs, 14 (38%) reoccluded within 1 month. A higher proportion of patients initially treated with one rt-PA (71%) experienced another CVC dysfunction within 1 month, compared with 29% CVC dysfunction in those requiring >1 dose. CONCLUSIONS: This article describes the use of rt-PA (0.5 mg, without dose escalation) to lyse CVC-associated thrombi specifically in small children with cancer, a patient population in which it is particularly desirable to minimize the degree of fibrinolysis. One dose of 0.5 mg rt-PA, with an additional dose if necessary, is as safe and effective as previously reported escalating dose regimens for CVC clot lysis. There is no statistically significant correlation of treatment failure with patient age, weight, or catheter lumen size, and no significant propensity for rapid rethrombosis following a single dysfunction and treatment. Patients initially treated with a single dose of rt-PA appear to have more subsequent dysfunctions in the month after treatment, an observation that warrants further study.     

Heparin-induced thrombocytopenia type II in an infant with a congenital heart defect--anticoagulation during cardiopulmonary bypass with epoprostenol sodium and heparin.

BACKGROUND: Heparin-induced thrombocytopenia type II (HIT II) is a rare but potentially life-threatening complication of heparin therapy. Hitherto, only few reports on HIT II in infants and children have been published. In particular, infants and children who have to be operated under cardiopulmonary bypass are at risk as an alternative anticoagulation is required. CASE PRESENTATION: We report on an infant with a congenital heart defect who was scheduled for cardiac surgery (Damus Kaye-Stansel procedure) with cardiopulmonary bypass. In the intensive care unit, an HIT II was diagnosed. Before surgery, the infant was pretreated with epoprostenol sodium (incrementally increasing up to a maximum dose of 30 ng/kg/min) before heparin was administered shortly after sternotomy. Mean arterial pressure was kept stable with an infusion of norepinephrine and the course of the cardiopulmonary bypass showed no signs of thrombosis. Drainage loss in the postoperative period was moderate. CONCLUSION: In HIT II infants, pretreatment with epoprostenol sodium before reexposure to heparin may offer a safe and effective anticoagulation for cardiopulmonary bypass.     

Prophylactic use of clopidogrel in paediatric cardiac patients

Thromboembolic complications in infants with congenital heart defects are common despite inhibition of platelet function with acetylsalicylic acid (ASS). Yet there is still insufficient pharmacologic data on the use of clopidogrel in infants. The adult dose of 75 mg/d is significantly higher than the dose lately recommended in infants (0.2 mg/kg/d). Moreover, we know of nonresponders to both acetylsalicylic acid and clopidogrel. Normal coagulation tests fail to identify those patients.Prospective monocentric study on 14 children (median age 5, range 0.7-84 months, 9 male, 5 female). Shunt thrombosis had occurred in 4 infants on ASS therapy. Seven days after starting clopidogrel (0.2 mg/kg/d), platelet function was tested by stimulation with ADP (4 and 10 μmol/l). We considered the range for the clopidogrel effect to be optimal if the maximum aggregation on ADP 4 μmol/l was between 30-50%.Clopidogrel 0.18-0.24 mg/kg/d in addition to ASS 2-4 mg/kg/d resulted in effective inhibition of platelet function in 93% (ADP 4 μmol/l: median 38%, range 30-63). All patients were responders. We observed neither any thromboembolic events nor severe bleeding episodes during the median 11-month follow-up period (range 1-30 mo).Testing platelet function makes clopidogrel dosing safer, and simplifies therapy adjustments in long-term treatment. A clopidogrel dose of 0.2 mg/kg/d was safe and effective in combination with ASS in this small patient cohort.     

Oral D‐penicillamine for the prevention of retinopathy of prematurity in very low birth weight infants: a randomized,placebo‐controlled trial

Purpose: To compare prophylactic enteral D‐penicillamine (DPA) with placebo for prevention of ‘retinopathy of prematurity (ROP) or death’ among very low birth weight (VLBW) infants. Methods: This was a double‐blind, single‐centre, randomized, placebo‐controlled trial with stratification (for birth weight <1250 and ≥1250 g) and blocking. Inborn neonates with birth weight 750–1500 g, gestation ≤32 weeks, age ≤5 days, who tolerated feeds were eligible. Neonates with gastro‐intestinal malformations, life‐threatening malformations and necrotizing enterocolitis were excluded. Enrolled subjects were randomly allocated to receive oral DPA suspension at 100 mg/kg/dose 8 h for 3 days, followed by 50 mg/kg/day for another 11 days or placebo. The primary outcome was ‘any ROP or death’. Secondary outcomes included any ROP, treatable ROP, adverse effects and feed intolerance. Results: A total of 88 subjects were enrolled. Baseline characteristics were similar with the exception of multiple gestation. There were no significant differences in primary and secondary outcomes, even after adjusting for multiple gestation and on sub‐group analysis. No adverse reaction was noted. Conclusion: Prophylactic enterally administered DPA suspension in a dose 100 mg/kg/dose 8 h for 3 days, followed by 50 mg/kg once per day for next 11 days, does not prevent ‘any stage ROP or death’ or ‘ROP requiring treatment’ in VLBW infants. DPA is well tolerated and does not have any major short‐term adverse effects.     

Effect of decreased umbilical blood flow and hemorrhage, and decreased prostaglandins on the ductus venosus diameter in the rat

BACKGROUND: The closing mechanisms of the ductus venosus (DV) have not yet been revealed. OBJECTIVES: The aims of this study were to document the perinatal closing process of the DV, to study the suppression of prostaglandins by indomethacin, and to determine the effects of umbilical blood flow to the fetal DV. METHODS: The proximal and distal DV diameters were studied in near-term fetal and neonatal rats with the rapid whole-body freezing method. RESULTS: The DV diameter changed sensitively at birth, and decreased by 10% immediately after the cessation of the umbilical circulation. Umbilical hemorrhage caused an additional decrease in the DV diameter compared with neonate without the hemorrhage. The neonates showed a DV diameter decreased by 20% at 30 min and 30% at 60 min after birth. The fetal DV was tubular, and the neonatal DV was horn-shaped with a smaller inlet than outlet. A small dose (0.1 mg/kg) of indomethacin administered to the pregnant rats induced a reduction in prostaglandins and decreased the fetal DV diameter to 80% of the control. Indomethacin at a large dose (10 mg/kg), administered to the dams, induced a reduction in prostaglandins, severe constriction of the ductus arteriosus, and decreased blood flow through the descending aorta umbilicus, and caused a further reduction in the DV diameter to 70-80% of the control. A large dose of nifedipine (10 mg/kg), which causes cardiac suppression and heart failure in the fetus, was administered to near-term rats to study the effect of decreased fetal cardiac output and blood flow passing through the DV. Nifedipine induced a 20% decrease in the DV diameter for 2-8 h. In all 1-hour-old neonates with or without pretreatment, the inlet diameter of the DV was reduced more than the outlet diameter, and the DV showed a horn-shaped morphology. CONCLUSION: In conclusion, perinatal cessation of the umbilical circulation and umbilical hemorrhage are associated with an immediate decrease in DV diameter. The DV diameter is also reduced in other conditions associated with decreased umbilical blood flow, such as induced by nifedipine which leads to heart failure and constricting of the ductus arteriosus induced by indomethacin. The constricting effect of a small dose of indomethacin suggests that prostaglandins dilate the DV physiologically.     

The effects of early postnatal dexamethasone therapy on pulmonary outcome in premature infants with respiratory distress syndrome: a two-year follow-up study

AIM: To evaluate the pulmonary outcome at corrected age of 2 y on preterm infants who participated in a double-blind trial of early postnatal dexamethasone therapy (< 12 h after birth) for the prevention of chronic lung disease. METHODS: Clinical respiratory status, blood gases, acid-base balance and pulmonary function were evaluated at corrected age of 2 y in 116 preterm infants (59 infants in the control group; 57 in the dexamethasone-treated group). In the dexamethasone-treated group, dexamethasone was administered intravenously every 12 h in tapering doses: 0.25 mg/kg on days 1 through 7, 0.12 mg/kg on days 8 through 14, 0.05 mg/kg on days 15 through 21, and 0.02 mg/kg on days 21 through 28. RESULTS: The clinical and laboratory characteristics in the perinatal period were comparable between the groups. At the time of follow-up (mean +/- SD corrected age was 25.1 +/- 4.8 mo for the control group and 24.6 +/- 5.1 mo for the dexamethasone-treated group), there was a slightly lower mean body weight and body length, and a lower psychomotor developmental index in the dexamethasone-treated group than in the control group (10.9 +/- 2.1 vs 11.5 +/- 1.9 kg, 84.4 +/- 6.1 vs 85.9 +/- 5.8 cm, and 82 +/- 24 vs 89 +/- 26, respectively); however, these differences were not statistically significant. There were no significant differences between the control and dexamethasone-treated groups in clinical respiratory status, blood gases, acid-base balance or in lung mechanics (V(T): 9.5 +/- 2.0 vs 9.4 +/- 1.9 ml/kg; V(min): 0.23 +/- 0.04 vs 0.23 +/- 0.03 l/min/kg; C(RS): 13.1 +/- 3.9 vs 12.6 +/- 3.6 ml/kPa/kg; R(RS): 1.56 +/- 0.64 vs 1.62 +/- 0.58 kPa/l/s, respectively). CONCLUSION: There was no apparent adverse respiratory outcome associated with early postnatal dexamethasone therapy.     

Topotecan in the treatment of refractory neuroblastoma and other malignant tumors in childhood - a phase-II-study

BACKGROUND: The topoisomerase-I-inhibitor Topotecan (TPT) has shown a broad activity in the therapy of adult malignant diseases. In pediatric oncology TPT has been rarely used. METHODS: From 1/98 to 8/99 we conducted a multicenter phase-II-study of TPT (1.5 mg/m (2)/d in 30 min i. v. for 5 days every 21 days) in pediatric patients (pts) with malignant tumors refractory to conventional therapy (either second line or any relapse). PATIENTS: A total of 20 pts received 81 cycles. The 7 female and 13 male pts had a median age of 10.2 years at the beginning of the TPT therapy. RESULTS: The median number of administered TPT cycles was 4 with an interval of 23.5 days. The median administered TPT dose was 1.48 mg/m (2)/d. No complete responses, but 2 partial responses and 9 stable diseases were observed. In 9 pts the disease progressed. The mean duration until progression for SD was 130 and not different from PR with 131 days. The median cumulative TPT dose until progression in responders was 30 mg/m (2). For all study-pts the median overall survival time was 235 days with 1 pt. still alive. The main toxicity was hematological with anemia grade III/IV (10/42 % of all evaluable TPT cycles), neutropenia grade III/IV (49/18 %) and thrombopenia grade III/IV (35/36 %). Non-hematologic toxicity was mild with the exception of 4 cycles with infection grade III and 1 grade IV. No patient died of therapy-related complications. CONCLUSIONS: TPT as monotherapy has shown an antitumor activity in pediatric pts with various malignancies. Toxicity was mainly hematological and manageable. Further evaluation of TPT treatment is planned using combinations with other cytostatic drugs.     

Recombinant plasminogen activator therapy for cerebral vein thrombosis in a child carrier of prothrombin gene mutation

Venous thrombosis of transverse and sigmoid sinuses was diagnosed in a 3-year-old child who is a carrier of the G20210A prothrombin gene mutation. Recombinant tissue plasminogen activator (rt-PA) treatment was started 9 days following the onset of neurologic signs. Nine days of rt-PA therapy completely dissolved the thrombus. This case provides further evidence that rt-PA is useful and safe in children with thrombosis.