Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study.

We report on the outcome of children with advanced primary myelodysplastic syndrome (MDS) transplanted from an HLA-matched sibling (MSD) or an unrelated donor (UD) following a preparative regimen with busulfan, cyclophosphamide and melphalan. Ninety-seven patients with refractory anemia with excess blasts (RAEB, n=53), RAEB in transformation (RAEB-T, n=29) and myelodysplasia-related acute myeloid leukemia (MDR-AML, n=15) enrolled in the European Working Group of MDS in Childhood (EWOG-MDS) 98 study and given hematopoietic stem cell transplantation (HSCT) were analyzed. Median age at HSCT was 11.1 years (range 1.4-19.0). Thirty-nine children were transplanted from an MSD, whereas 58 were given the allograft from a UD (n=57) or alternative family donor (n=1). Stem cell source was bone marrow (n=69) or peripheral blood (n=28). With a median follow-up of 3.9 years (range 0.1-10.9), the 5-year probability of overall survival is 63%, while the 5-year cumulative incidence of transplantation-related mortality (TRM) and relapse is 21% each. Age at HSCT greater than 12 years, interval between diagnosis and HSCT longer than 4 months, and occurrence of acute or extensive chronic graft-versus-host disease were associated with increased TRM. The risk of relapse increased with more advanced disease. This study indicates that HSCT following a myeloablative preparative regimen offers a high probability of survival for children with advanced MDS.

[Hereditary head and neck tumors]. / Hereditäre Tumoren des Kopf-Hals-Bereichs.

Hereditary paraganglioma, Gorlin-Goltz syndrome and Fanconi anemia are among the rare hereditary tumor syndromes of the head and neck. Patients with hereditary paraganglioma often develop multiple tumors of the glomus caroticum and glomus jugulotympanicum. The corresponding genetic defects of the mitochondrial succinate dehydrogenase complex induce autonomous tumor cell growth. In patients with Gorlin-Goltz syndrome basal cell carcinomas and keratocystic odontogenic tumors usually occur much earlier than in patients with sporadic tumors. The associated germline mutations are located in the patched gene which is a modulator of the cell cycle. Fanconi anemia represents a chromosomal instability syndrome which is characterized by early onset of pancytopenia, i.e. bone marrow failure and subsequent development of acute myeloid leukemia and/or squamous cell carcinomas, especially of the head and neck. A total of 13 different gene clusters have been identified in 2 DNA associated complexes which play an important role in DNA repair mechanisms.

Ulcerative tracheitis among intubated neonates--a clinicopathologic study.

OBJECTIVE: To determine frequency of ulcerative tracheitis (UT) among intubated neonates and identify groups of neonates at greater risk of UT. METHODS: Medical histories and autopsy findings from 232 neonates between 1995 and 2006 were reviewed retrospectively. All neonates were treated at the Department of Neonatology, Clinical Hospital Center Split. Autopsies and histological examinations were performed at the Clinical Department of Pathology, Forensic Medicine and Cytology. Neonates were classified into groups based on their sex, gestational age, survival time and cause of death, duration and reasons for intubation. Simplified Wigglesworth classification was used to determine cause of death. Chi-squared test and multiple logistical regression analysis were used for statistical analysis. RESULTS: UT was found in 44 cases (18.96%). The main risk factor for UT development was duration of intubation, especially if it lasted over 96 h (P=0.005). Higher frequency of UT was noted in neonates with gestational age over 37 weeks (P=0.002) and birth weight over 2500 g (P=0.115). CONCLUSION: Our study has shown that the main risk factor for UT development was intubation duration exceeding 96 h. Term-borns, and neonates with normal birth weight both have higher risk of UT. High risk groups should be observed carefully and alternative respiratory support treatment, such as continues positive airway pressure (CPAP) may be considered.

Ectopic development of skeletal muscle induced by subcutaneous transplant of rat satellite cells.

The present study analyzes the ectopic development of the rat skeletal muscle originated from transplanted satellite cells. Satellite cells (10(6) cells) obtained from hindlimb muscles of newborn female 2BAW Wistar rats were injected subcutaneously into the dorsal area of adult male rats. After 3, 7, and 14 days, the transplanted tissues (N = 4-5) were processed for histochemical analysis of peripheral nerves, inactive X-chromosome and acetylcholinesterase. Nicotinic acetylcholine receptors (nAChRs) were also labeled with tetramethylrhodamine-labeled alpha-bungarotoxin. The development of ectopic muscles was successful in 86% of the implantation sites. By day 3, the transplanted cells were organized as multinucleated fibers containing multiple clusters of nAChRs (N = 2-4), resembling those from non-innervated cultured skeletal muscle fibers. After 7 days, the transplanted cells appeared as a highly vascularized tissue formed by bundles of fibers containing peripheral nuclei. The presence of X chromatin body indicated that subcutaneously developed fibers originated from female donor satellite cells. Differently from the extensor digitorum longus muscle of adult male rat (87.9 +/- 1.0 microm; N = 213), the diameter of ectopic fibers (59.1 microm; N = 213) did not obey a Gaussian distribution and had a higher coefficient of variation. After 7 and 14 days, the organization of the nAChR clusters was similar to that of clusters from adult innervated extensor digitorum longus muscle. These findings indicate the histocompatibility of rats from 2BAW colony and that satellite cells transplanted into the subcutaneous space of adult animals are able to develop and fuse to form differentiated skeletal muscle fibers.

Ectopic development of skeletal muscle induced by subcutaneous transplant of rat satellite cells

The present study analyzes the ectopic development of the rat skeletal muscle originated from transplanted satellite cells. Satellite cells (10(6) cells) obtained from hindlimb muscles of newborn female 2BAW Wistar rats were injected subcutaneously into the dorsal area of adult male rats. After 3, 7, and 14 days, the transplanted tissues (N = 4-5) were processed for histochemical analysis of peripheral nerves, inactive X-chromosome and acetylcholinesterase. Nicotinic acetylcholine receptors (nAChRs) were also labeled with tetramethylrhodamine-labeled alpha-bungarotoxin. The development of ectopic muscles was successful in 86 percent of the implantation sites. By day 3, the transplanted cells were organized as multinucleated fibers containing multiple clusters of nAChRs (N = 2-4), resembling those from non-innervated cultured skeletal muscle fibers. After 7 days, the transplanted cells appeared as a highly vascularized tissue formed by bundles of fibers containing peripheral nuclei. The presence of X chromatin body indicated that subcutaneously developed fibers originated from female donor satellite cells. Differently from the extensor digitorum longus muscle of adult male rat (87.9 ± 1.0 æm; N = 213), the diameter of ectopic fibers (59.1 æm; N = 213) did not obey a Gaussian distribution and had a higher coefficient of variation. After 7 and 14 days, the organization of the nAChR clusters was similar to that of clusters from adult innervated extensor digitorum longus muscle. These findings indicate the histocompatibility of rats from 2BAW colony and that satellite cells transplanted into the subcutaneous space of adult animals are able to develop and fuse to form differentiated skeletal muscle fibers.

Middle cerebral artery velocity waveforms in fetuses with absent umbilical artery end-diastolic flow.

Middle cerebral artery (MCA) velocity waveforms were analyzed in 21 fetuses with absent umbilical artery end-diastolic flow (AEDF). Resistance index (RI) was measured from MCA velocity waveforms when AEDF was observed for the first time and at consecutive examinations. Fetal distress defined by fetal heart rate monitoring was found in 19 cases (90%). The difference between MCA RI values of first and last examinations was statistically significant (p < 0.01). There was a positive correlation between MCA RI values at the first examination and the time passing to delivery (r = 0.52; p < 0.05). There was no significant correlation between MCA RI values and the incidence of an adverse perinatal outcome. Pregnancies with AEDF are of high risk for the development of fetal distress. MCA resistance index values decrease gradually in fetuses with AEDF suggesting continuous reduction of cerebral vascular resistance during chronic fetal hypoxia.

[Risk of abnormal absorption of lead in glass decoration workers]. / Rischio di abnorme assorbimento di piombo nella decorazione del vetro.

Following the observation of an abnormal lead absorption (PbB 72 micrograms/100 ml) in a young female glass decorator on a routine laboratory test, blood lead levels were measured in glass decorators of the entire area of the Local Health Unit of Treviso (Northern Italy). Abnormal lead absorption was found in a large number of glass workers, the source of exposure being the high content of inorganic lead in the "low-melting" paints that were used (brush and spray painting). Most of the exposed workers were females of fertile age, for whom even a moderate exposure to inorganic lead may constitute a risk during pregnancy. Attempts to reduce lead exposure levels by means of a health education programme and environmental improvements at the workplace were unsuccessful. In conclusion, a reduction in lead absorption in female glass decoration workers can only be achieved by using "low-melting" paints with a lower lead content.

Clinical experience of electronic peroneal stimulators in 50 hemiparetic patients.

Fifty hemiparetic subjects were selected from a population of 250 patients according to criteria forsuitable candidates for peroneal stimulation. The patients received from 10 to 120 hours of treatment during 2--5 weeks. The therapeutic results obtained were classified into four groups, ranging from none to excellent improvement of voluntary movement and reduction of spasticity. The clinical results were correlated to different variables where time from lesion, spasticity, and extent of treatment appeared to be the most important ones. The percentage of excellent results decreased with increasing time from lesion and spasticity, and increased with increasing treatment. Orthotic validity (i.e. the beneficial effect of the orthosis) was observed in 76% of the selected cases and in most of them it was very significant. Preliminary tests performed on 9 subjects showed that in cases with orthotic validity the peroneal brace slightly reduces the oxygen consumption of patients and improves their motivation. This work gives a more quantitative perspective of the validity of functional peroneal stimulation and a better indication of criteria for patient selection. The overall validity of an electronic peroneal brace appears to apply to 15% of the total ambulatory hemiparetic population and its therapeutic value is relevant in two-thirds of such cases if sufficient treatment is provided. Application of functional electrical stimulation to non-ambulatory subjects in the acute phase may however lead to a higher percentage of cases of therapeutic validity.