1,721,006 research outputs found
Failure of immunoglobulins to prevent neonatal thrombocytopenia in mothers with immunothrombocytopenic purpura
No full textWe report the case of a full-term (gestational age: 39 weeks) female newborn of a mother affected by immunothrombocytopenic purpura, treated with a high total dose (2 g/kg) of intravenous IgG, administered over a 3-day period starting 3 days before delivery. Infant platelet count at birth was 20,000/mm3 and she showed a great number of petechiae on the first day of life. After a random donor platelet transfusion and treatment with intravenous high-dose IgG (400 mg/kg for 5 days), platelet count began to increase. We conclude that exogenous IgG, even at high concentrations, apparently does not significantly cross the placenta, despite adequate maternal blood levels
Role of {[I-131]metaiodobeuzylguanidine (MIBG) in the treatment of neuroblastoma: A review}
No full textFor years there has been no substantial improvement in survival rates of
children with advanced neuroblastoma (NB). NB is a radiosensitive tumor.
Since promising results are obtained with aggressive chemotherapy, it
might be expected that even better results could be obtained from a high
radiation dosage. But delivery of high radiation doses is limited by
host intolerance. {[I-131]Metaiodobeuzylguanidine ([I-131]MIBG), a
radioiodinated aralkylguanidine, is capable of competing with
norepinephrine for uptake into neuroadrenergic tissue and derived
tumors. Targeted radiotherapy with elevated doses has been pioneered by
several groups, as a high dose of radioactivity can be selectively
delivered to tumor cells, with an acceptable systemic toxicity. We
briefly review here the latest research achievements and the progress
that has been made with the use of this new treatment modality in
patients with advanced NB. Encouraging results have been obtained with
[I-131]MIBG in patients with resistant disease; however, a promise for
the future may lie in tentative therapeutic approaches with
[I-131]MIBG used at the time of diagnosis. The toxicity of
[I-131]MIBG de novo contrasted with previous experience in
[I-131]MIBG therapy in pretreated patients with relapses, since bone
marrow depression did not appear to be very significant. We have
recently investigated a new therapeutic approach to stage IV NB using a
combination of [I-131]MIBG and cisplatin. Our results, although
preliminary, suggest that this combined therapy is most effective in
pretreated stage IV NB. However, relatively severe and long-lasting
hematologic toxicity has been observed. We are at present trying to
reduce the possible toxic synergism between cisplatin and [I-131]MIBG.
Th, real therapeutic potential of radioiodinated MIBG in patients with
NE has not yet fully explored. Future improvements may result from the
contribution of further clinical and research investigations.
CARBOPLATIN IN CHILDHOOD MEDULLOBLASTOMA PNET - FEASIBILITY OF AN IN-VIVO SENSITIVITY TEST IN AN UP-FRONT STUDY
No full textSixteen patients with high risk MB/PNET at diagnosis were included in a
pilot study employing carboplatin (CBDCA) as a single drug prior to
conventional therapy. The main goal of the study was to identify in a
short-term trial a significant response that would predict further
response to CBDCA in the single patient. Exploration of CBDCA activity
was focused on response after the first course as compared to the
response following the second course. A course consisted of CBDCA 600
mg/m2 on days 1 and 2 administered in a 1 h infusion to be repeated 3-4
weeks later. After two cycles we observed 1 CR and 9 PR, that is a 62\%
response rate. The first course resulted in 5 PR, 5 MR, SD, and 1 PD;
after the subsequent course in all responding patients, response
persisted or improved whereas in no patient with SD any improvement was
observed. The correlation of response to the first course with response
to the second course was statistically significant (P = 0.0009). The
main toxicity of the single course was hematologic and consisted of
rapidly reversible grade 3-4 neutropenia and thrombocytopenia in 94\% of
patients. Pharmacokinetic studies showed a very limited interpatient
variability of both Cmax 57.6 +/- 9.9 mug/ml) and AUC (15.3 +/- 1.5
mg/ml . min) of free CBDCA, which eliminates an important variable in
the evaluation of response. In conclusion, this `'in vivo test'' appears
effective, reasonably safe, and reproducible in identifying patients
likely to benefit from CBCDA: after a period of time as short as 3-4
weeks following the first course, multidrug chemotherapy including CBDCA
may be employed in the responding patients, whereas an alternative
regimen would be indicated in the non-responding patients. (C) 1995
Wiley-Liss, Inc
[Type of diet and "ambulatory" pathology in the first 6 months of life]
No full textThis work is a contribution to the investigation that mainly in the last year have been widely performed to evaluate the protecting action of breast feeding against some typical pathological occurrences in the first months of life. Authors studied, for six months, 117 babies. The respiratory and intestinal illness have been found (in progress or anamnestically) during pediatric monthly or occasionally visits. 33% of the babies were fed with milk formula since the first life months; the remainder 67% were breastfed during one month at least. By statistic correlation of type of feeding and disease frequency, there is evidence of the following: 1) Babies, breastfed during 6 months, have lower frequency of respiratory pathology, when compared (p 0.05) with 6 months bottle fed ones. 2) Babies, breastfed during 2 months have lower frequency of intestinal pathology when compared (p 0.05) with bottle fed ones. Therefore, it seems that the most interesting results coming out from this study is that the protective action of breast feeding concerns not only the intestinal disease, but the respiratory ones too, when, however, the breast feeding period is enough extended
A NEW APPROACH IN THE TREATMENT OF STAGE-IV NEUROBLASTOMA USING A OMBINATION OF {[I-131] METAIODOBENZYLGUANIDINE (MIBG) AND CISPLATIN}
No full textThe outlook for disseminated neuroblastoma (NB) continues to be dismal.
NE is a radiosensitive tumour. Owing to its high concentration in NE
lesions, {[I-131]meta-iodobenzylguanidine [I-131]MIBG has the
potential for specifically delivering very large radiation doses to the
malignant cells. Encouraging results have been reported with
[I-131]MIBG used alone in patients resistant to conventional therapy
and at diagnosis. We report the first attempt to explore the integration
of this new treatment modality with chemotherapy. Among the drugs
effective in NE, cisplatin was chosen because of its high degree of
activity against NE, its mild haematological toxicity and the known
synergism between cisplatin and radiation. 4 patients, 3 with relapsed,
heavily pre-treated, progressive stage IV NE, and 1 with stage IV NE at
diagnosis, all with a good [I-131]MIBG uptake, were investigated with
combined therapy (CO-TH). Two complete remissions and one partial
remission were observed in these patients 4-6 weeks following only a
single course of both cisplatin and [I-131]MIBG, `'standard'' dosage.
The only toxicity was haematological, which was significant and
relatively long-lasting, but was not associated with any serious
infections or bleeding tendency. The general condition of these patients
during the entire study period was excellent. The fourth patient,
investigated at diagnosis with a modified less intensive treatment,
obtained a partial remission with mild haematological toxicity. During
the subsequent courses of intensive multidrug chemotherapy, this patient
showed haematological toxicity comparable with that experienced by
patients treated with an identical drug combination, but without
previous treatment with CO-TH. The provisional conclusion of this
ongoing study is that this new form of CO-TH appears most effective in
obtaining a rapid and excellent response in heavily pretreated relapsed
patients with progressive disease, and should be further investigated in
earlier stages of the disease.
Optimal use of the 131-I-metaiodobenzylguanidine and cisplatin combination in advanced neuroblastoma
No full textNeuroblastoma (NB), a childhood radiosensitive tumor, is very aggressive
and malignant; in its disseminated form, despite very intensive
chemotherapy, prognosis continues to be dismal. Owing to its capacity to
concentrate in NE lesions, large doses of 131-I-MIBG, have given very
encouraging therapeutic results in patients resistant to conventional
therapy as well as at diagnosis.
We recently reported the first attempt in combination therapy (CO-TH)
using 131-I-MIBG and cisplatin. This new form of CO-TH appears very
effective in obtaining a rapid and excellent response in relapsed
patients.
In this report, we describe the results of further experience with CO-TH
in disseminated NE. We have attempted to verify to what extent
interaction between the effects of the two agents may produce
therapeutic benefit, and we have sought the optimization of CO-TH use.
Three stage IV NE patients were treated with CO-TH. The following
treatment schedule, was planned: day 1, cisplatin 50 mg/m(2) i.v. over 6
h; day 2, 131-I-MIBG 100-130 mCi at high specific activity (-1.1 Gbq/mg)
i.v. over 6 h followed, a week later, by the same treatment combination.
The therapeutic results were encouraging. However, hematological
toxicity continued to represent a major limiting factor. In view of the
overall effectiveness of CO-TH, at the price of lasting hematological
toxicity, it may be indicated as a consolidation regimen some time
before conditioning chemotherapy for autologous bone marrow
transplantation
La patologia polmonare cronica nel neonato pretermine
No full textLa patologia polmonare cronica nel neonato pretermin
A human neuroblastoma xenograft model for 125-I-metaiodobenzylguanidine biodistribution studies
No full textWe developed an animal model to evaluate the
125-I-metaiodobenzylguanidine (125-I-mIBG) biodistribution in tumor
bearing mice. Six weeks old nude-atimic mice were subcutaneously
injected with 30 x 10(6) cells of the human neuroblastoma (NB) cell line
SH-SY5Y. TE-671, a rhabdomyosarcoma cell line, was used as a control
tumor without a specific mIBG uptake mechanism. In order to prevent
possible tumor rejection mediated by NK activity the anti asialo GM1
antiserum was administered intraperitoneally once a week for 4 weeks.
The maximum anti asialo mediated effect was obtained by administering
the first dose the same day as the cell implant. In this group of
animals by 9 weeks 98\% of mice had a measurable tumor. We have utilized
this model to evaluate the biodistribution of 125-I-mIBG given as two
different formulations: standard preparation with a specific activity of
84 mCi/mg and the no carrier added (n.c.a.) formulation with a specific
activity of approximatelly 8,000 mCi/mg. Our preliminary results
indicate that the biodistribution of the two different formulations in
the various organs are similar. Therefore it appears that n.c.a. mIBG
should not cause an increased toxicity in possible normal target organs
such as heart or adrenals. Additional experiments will be performed in
this model to ascertain if there is a potential advantage of the
clinical use of n.c.a. mIBG over the standard preparation
CLINICAL PHARMACOKINETICS OF CARBOPLATIN IN CHILDREN
No full textThe present study was undertaken to evaluate in children the plasma
pharmacokinetics of free carboplatin given at different doses and
schedules and to evaluate the inter- and intrapatient variability and
the possible influence of schedule on drug exposure. A total of 35
children (age range, 1-17 years) with malignant tumors were studied. All
patients had normal renal function (creatinine clearance corrected for
surface body area, above 70 ml min(-1) m(-2); range, 71-151 ml min(-1)
m(-2)) and none had renal involvement by malignancy. Carboplatin was
given at the following doses and schedules: 175, 400, 500, and 600 mg/
m(2) given as a l-h infusion; 1,200 mg/m(2) divided into equal doses and
infused over 1 h on 2 consecutive days; and 875 and 1,200 mg/m(2) given
as a 5-day continuous infusion. A total of 57 courses were studied.
Carboplatin levels in plasma ultrafiltrate (UF) samples were measured
both by high-performance liquid chromatography and by atomic absorption
spectrophotometry. Following a 1-h infusion, carboplatin free plasma
levels decayed biphasically; the disappearance half-lives, total body
clearance, and apparent volume of distribution were similar for
different doses. In children with normal renal function as defined by
creatinemia and blood urea nitrogen (BUN) and creatinine clearance, we
found at each dose studied a limited interpatient variability of the
peak plasma concentration (C-max) and the area under the
concentration-time curve (AUC) and a linear correlation between the dose
and both C-max (r = 0.95) and AUC (r = 0.97). The mean value +/- SD for
the dose-normalized AUC was 13+/-2 min m(2) 1(-1) (n = 57). The
administration schedule does not seem to influence drug exposure, since
prolonged i.v. infusion or bolus administration of 1,200 mg/m(2)
achieved a similar AUC (13.78+/-2.90 and 15.05+/-1.44 mg ml(-1) min,
respectively). In the nine children studied during subsequent courses a
limited interpatient variability was observed and no correlation (r =
0.035) was found between AUC and subsequent courses by a multivariate
analysis of dose, AUC, and course number. The pharmacokinetic parameters
were similar to those previously reported in adults; however, a weak
correlation (r = 0.52, P = 0.03) between carboplatin total body
clearance and creatinine clearance varying within the normal range was
observed. A dosing formula appears unnecessary in children with normal
renal function since a generally well-predictable free carboplatin AUC
is achieved following a given dose
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