Metastatic neuroblastoma demonstrated by whole-body PET-CT using 11C-HED.
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Biomedical subjects
Publications and source records attributed to B Rath.
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OBJECTIVE: In recent years, it has been proposed that nephrotic syndrome is a consequence of an imbalance between oxidant and anti-oxidant activity. In the present study, the levels of micronutrient anti-oxidant vitamins (vitamin E, vitamin C, carotene and riboflavin) in Indian children with steroid responsive nephrotic syndrome were investigated. Their levels were measured during the acute proteinuric phase of the disease, as well as during clinical recovery (remission), in order to understand the possible role of nutritionally modifiable anti-oxidants in the aetiopathogenesis of the disease. METHODS: The study was a hospital based, prospective cohort study. Serum and erythrocyte vitamin E, leucocyte vitamin C, serum carotene, erythrocyte riboflavin activity and serum malonyldialdehyde (MDA) levels were measured in 30 consecutive cases of children with nephrotic syndrome (International Study of Kidney Diseases in Children (ISKDC) criteria) during the proteinuric phase of the disease and at 4 weeks after remission was induced by steroid therapy. The same biochemical parameters were measured in healthy siblings (controls) of the 30 patients. RESULTS: Mean vitamin E (serum and erythrocyte), vitamin C and carotene were significantly lower during the proteinuric phase of the disease, and there was decreased erythrocyte riboflavin activity. There was significant elevation in the serum level of MDA during this phase. In addition, all these parameters tended to improve during remission, although complete normalization did not occur. CONCLUSION: These vitamins were active in performing their anti-oxidant function, as indicated by significant depression in their levels during the acute (proteinuric) phase, followed by partial recovery during remission. It may be concluded that steroid responsive nephrotic syndrome in children is associated with oxidative stress.
OBJECTIVES: The usage of gloves in dentistry has increased greatly over the last 10 years and this has highlighted certain problems when gloves are being worn extensively. While skin irritations and allergies caused by latex proteins and accelerators have been the main focus of attention, dental materials such as disinfectants have also become known as a source of skin reactions. This study was performed to evaluate the permeability of various gloves by ethanol. METHODS: The tip of the middle finger of 13 glove brands (natural latex gloves (NLG) powdered or unpowdered, powdered vinyl, nitrile and synthetic elastomer) was exposed to 5 ml of a hand disinfectant (Desderman). After a penetration time ranging from 2 min to 8 h the permeation of Desderman was detected with a gas chromatograph. RESULTS: Only one component of the disinfectant (ethanol) could be detected to have gone through the gloves. After only 2 min the vinyl and one nitrile glove and after 10 min all glove types were permeated. Powder seemed to have no real influence on the penetration of ethanol. Some natural latex gloves showed a low rate of leakage, while vinyl and nitrile gloves were penetrated quickly and to a great extent. The synthetic elastomer (Biogel Neotech) was the only one with a significantly lower penetration even after 2-8 h. SIGNIFICANCE: While there are reports of adverse skin reactions to alcohol the amount of ethanol (up to 40 microliters after 2 h) detected in this study is much too low to cause irritations and certainly not toxicity, but it could possibly initiate allergic reactions.
AIMS: To test the hypothesis that oxygen free radicals are mediators of excessive protein permeability in steroid responsive nephrotic syndrome. DESIGN: Case control study. SUBJECTS PATIENTS: 20 children with steroid responsive nephrotic syndrome; controls: 20 children admitted for elective surgery. SETTING: The paediatric and biochemistry departments of the Maulana Azad Medical College, New Delhi, India. METHODS: Blood samples were taken twice from children with nephrotic syndrome (on admission and on urinary remission) and once from controls. Biochemical assays were carried out on these blood samples to quantify the indirect markers of free radical injury in the body, namely: vitamin E, reduced glutathione (GSH), glucose-6-phosphate dehydrogenase (G6PD), malonyldialdehyde (MDA), and membrane cholesterol in erythrocytes. RESULTS: There was some evidence supportive of oxidative injury in the children with nephrotic syndrome in the form of greatly reduced concentrations of antioxidants vitamin E (155.4 microg/100 ml in controls, 86.4 microg/100 ml in patients) and G6PD (364 mU/ml in controls, 205.1 mU/ml in patients). However, concentrations of the oxidation byproduct MDA were raised only in the remission phase of the disease (0.984 nmol/ml in controls, 1.158 nmol/ml in cases), whereas those of GSH were unaltered. CONCLUSIONS: Changes in the concentrations of MDA, G6PD, and vitamin E are consistent with increased amounts of oxidation in steroid responsive nephrotic syndrome. Further research is needed to explain whether these changes are a cause or consequence of the disease.
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Native forms of asparaginase stem from different biological sources. Previously reported data from children treated with Erwinase showed significantly lower trough levels and pharmacokinetic dose intensity than after E. coli-derived preparations. Hence, schedule optimization was initiated to achieve relevant serum activities. 21 children on reinduction therapy received Erwinase on Mondays, Wednesdays and Fridays for 3 weeks (9 x 20000 IU/m2 i.v.) instead of 4x 10 000IU/m2 of E. coli asparaginase (twice weekly for 2 weeks). Asparaginase trough activities were measured as the primary parameter, targeting 100-200 IU/I after 2 d and >50 IU/l after 3 d. Concurrently, asparagine trough concentrations were monitored. The mean trough activity was 156+/-99 IU/l, with 2/108 samples showing no detectable activity. Regarding trough levels per individual (three or more measurements/patient), means ranged from 52+/-29 to 276+/-114 IU/l (20 patients, 106 samples), with nine, six, and five children inside, below, and above the target range, respectively. The mean 3 d trough activity was 50+/-39 IU/l (20 patients, 51 samples). In 11 of these samples no activity was measurable. Mean trough activities calculated per individual ranged from < 20-84+/-30 IU/l (14 patients, 42 samples) with seven children below the target limit of 50 IU/l and asparagine concentrations <0.2 - 1.5microM. We concluded that an increased dose of 9x20000 IU/m2 of Erwinia asparaginase within 3 weeks resulted in a pharmacokinetic dose intensity comparable to former observations made with 4 x 10 000IU/m2 of the E. coli product Crasnitin which is no longer marketed. High interindividual variability and the phenomenon of 'silent' inactivation necessitate monitoring wherever possible.
PURPOSE: To further reduce therapy-related late effects in patients with pediatric Hodgkin's disease (HD) while maintaining the high cure rates achieved with vincristine, prednisone, procarbazine, and doxorubicin (OPPA) or OPPA/cyclophosphamide, vincristine, prednisone, and procarbazine (COPP) chemotherapy and involved-field radiotherapy. The risk of testicular dysfunction was addressed by substituting etoposide for procarbazine (OEPA) in the induction therapy for boys. Radiation doses and fields were further reduced. PATIENTS AND METHODS: Three hundred nineteen boys and 259 girls younger than 18 years with previously untreated HD, enrolled onto the study between 1990 and 1995, were allocated to treatment group (TG)1 (early stages), TG2 (intermediate stages), or TG3 (advanced stages). All groups underwent two cycles of OEPA (boys) or OPPA (girls) for induction chemotherapy. TG2 and TG3 continued on additional two or four cycles, respectively, of COPP. Low-dose radiotherapy was given to the initially involved sites, ie, reduced involved fields. RESULTS: Initial response to OPPA or OEPA induction was virtually identical. Eight of 578 patients experienced early progression of HD. Thirty-seven relapses, three secondary tumors, and no secondary leukemias have been recorded, with a median follow-up duration of 5.1 years (maximum, 8.1 years). Thirteen of 578 patients died. The probability of 5-year event-free survival/overall survival is 91%/98% in the total group, 94%/97% with OPPA, and 89%/98% with OEPA induction therapy. Risk factor analysis showed two significant prognostic factors: histologic subtype NS2 and "B" symptoms. OEPA induction therapy, large mediastinal tumor, and age were not significant. Preliminary studies of testicular function indicate a lower risk of germ cell damage than previously documented with OPPA. CONCLUSION: OEPA is a satisfactory alternative to OPPA. Radiotherapy can be confined to involved sites when combined with appropriate chemotherapy. The DAL-HD-90 regimen represents a comprehensive treatment program for all stages of pediatric HD and offers a favorable benefit/risk ratio, combining excellent disease control, moderate acute toxicity, and reduced long-term toxicity.
Disseminated neuroblastoma after infancy has a prognosis of approximately 10-20% with conventional therapy. We investigated the role of high-dose chemotherapy (HDCT) with peripheral blood stem cell (PBSC) rescue in combination with 131I-metaiodobenzylguanidine ([131I-m]IBG). 11 children with neuroblastoma stage 4 were pretreated within the German Neuroblastoma Trial NB90 and included in a high-dose concept for consolidation. Remission was documented by ultrasound, CT, NMR, or [123I-m]IBG scanning. HDCT was a combination of melphalan (180 mg/m2), carboplatin (1,500 mg/m2) and etoposide (40 mg/kg). All children were treated by [131I-m]IBG (0.58 GBq/kg) prior to high-dose treatment. All 11 children were additionally treated with antiGD2 murine- or chimeric-antibody (ch14.18). 4 children had no change to their remission status but three achieved a complete response (from a partial response to first line) and one a partial response (from no response to first line). The other 3 children progressed, 2 dying of their disease. Using Kaplan-Meier analysis, the probability of progression-free survival was 0.70 +/- 0.15 with a median observation time of 19 months. 9/11 children are alive, 8 without progression or relapse, whilst 2 have died of their disease. The combination of mIBG plus high-dose chemotherapy with PBSC support supplemented by immunotherapy with antiGD2 antibody appears to be a feasible and effective treatment regimen for disseminated neuroblastoma in this limited series. Larger numbers of patients should be treated to confirm these results.
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PURPOSE: In newly diagnosed childhood acute lymphoblastic leukemia (ALL), a high tumor burden indicates a poor prognosis, while no such link has been established yet after relapse. The impact of the absolute peripheral blast count (PBC) at the time of relapse on the response to salvage chemotherapy after a late isolated bone marrow (BM) relapse is the subject of this prospective analysis. PATIENTS AND METHODS: Since 1983, 260 children with a first isolated BM relapse of ALL that occurred 6 months or later after elective cessation of front-line therapy were enrolled onto four consecutive multicenter trials of the Berlin-Frankfurt-Münster (BFM) Relapse Study Group. All patients received intensive multiagent induction and consolidation chemotherapy for 6 months, followed by maintenance therapy with methotrexate (MTX) and thioguanine for 2 years. Treatment of subclinical meningeal leukemia consisted of high-dose intravenous MTX and intrathecally administered cytostatic drugs, which was augmented by cranial irradiation since 1988. RESULTS: At the time relapse was diagnosed, PBC varied considerably among patients (median, 1,060/microL; range, 0 to 106,800/microL). Achievement of a second complete remission (CR) was not significantly different in children without detectable circulating blasts at relapse (37 of 38) and those with moderate (1 to 9,999/microL) PBC (165 of 171). In contrast, only 42 of 51 children with high PBC (> or = 10,000/microL) achieved a second CR (P = .0015). At a median follow-up time of 40 months, the 10-year event-free survival (EFS) probability was significantly (P = .0001) higher in children without circulating blasts (.64) than in children with moderate PBC (.32) or high PBC (.10). There was a preponderance of boys in the group without detectable circulating blasts, while the three PBC-defined groups did not differ with respect to frontline treatment, age at initial diagnosis, age at relapse, time off therapy, or salvage treatment protocol. On sequential univariate and multivariate analysis, only duration of first remission > or = 48 months was an additional independent indicator of adverse prognosis, while preventive cranial irradiation improved outcome independently of PBC. CONCLUSION: The absence of blasts on peripheral-blood smears at the time of a first late isolated BM relapse of childhood ALL is associated with a favorable response and prognosis in chemotherapy-treated children, who should be regarded as ineligible for bone marrow transplantation (BMT) unless a second round of chemotherapy has failed to produce a response.
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BACKGROUND: Diabetes insipidus renalis has only occasionally been reported in ifosfamide-induced renal Fanconi's syndrome, but in two studies on subclinical renal impairment, low morning urine osmolarity was found in high frequencies. This study was performed to assess the frequency of defective concentrating capacity in patients with ifosfamide-induced renal Fanconi's syndrome or severe impairment of proximal tubular function. PATIENTS AND METHODS: Seven patients with overt Fanconi's syndrome and 5 with a generalized but subclinical tubulopathy were examined. Beside proximal tubular solute reabsorption and estimation of glomerular filtration rate, urinary osmolarity was measured after overnight fast and DDAVP (1-D-amino-8-D-arginine vasopressin) testing. RESULTS: Five out of 7 patients with overt Fanconi's syndrome, but no patient with only subclinical tubular damage, had decreased osmolarities by at least one test. Increased sodium excretion was additionally found in 4 of these patients. CONCLUSION: Impaired renal concentrating capacity is a rare event in ifosfamide-induced renal dysfunction and confined to patients with overt Fanconi's syndrome. These patients should, however, undergo evaluation of concentrating capacity and renal sodium handling as decreased concentrating capacity and increased sodium excretion would render a patient at risk for dehydration episodes.
Twenty high risk children aged 5-12 years with various voiding problems were studied prospectively by urodynamics to evaluate the function of their urinary bladder and its continence mechanism. None of them had neuropathic bladder or any obstruction distal to bladder neck. Fourteen out of twenty (70%) had abnormal findings on urodynamics evaluation; 8 (40%) had non-neurogenic neurogenic bladder (NNNB); 3 (15%) had small capacity hypertonic bladder (SCHB); 2 (10%) had atonic bladder (AB) and 1 (5%) had hyperreflexic bladder (HB). We conclude that urodynamic abnormalities are as frequent in high risk Indian children as they are in developed countries. The high risk children should be subjected to urodynamic studies more frequently than being done hitherto and be directed to proper therapeutic modality.
A case of complete thrombosis of the superior sagittal sinus in a pregnant women with multiple haemorrhages and hydrocephalus is described. Due to acute onset and progressive neurological deterioration, the decision was taken to remove the clot surgically. A sinotomy was performed removing the thrombotic material followed by local infusion of tissue plasminogen activator (t-PA). The combination of surgical removal and thrombolysis was life-saving for this young patient.
Seventy-seven clinically normal children with kidneys of normal size were examined sonographically. Renal parenchymal volumes were calculated and related to age, height, body weight and body surface area; growth charts were constructed. A significant correlation was found between the renal parenchymal volume and the body somatometric parameters. The present report thus provides norms for renal parenchymal volume in Indian children.