Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow-derived hematopoietic stem cell transplantation: a 1-year follow-up.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of spinal cord and cortical motoneurons. Despite improved understanding of the mechanisms underlying ALS, in clinical practice the management of ALS remains essentially supportive and focused on symptom relief. However, over the past few years stem cell research has expanded greatly as a tool for developing potential new therapies for treating incurable neurodegenerative diseases. METHODS: Thirteen patients with sporadic amyotrophic lateral sclerosis (SALS) were included in this study, and bone marrow (BM)-derived hematopoietic progenitor stem cells were used. We selected patients with bulbar involvement and severe loss of movement. Our aim was to put the stem cells into the end of the brain stem and at the beginning of the spinal cord because the blood-brain barrier is intact in ALS and this region was the most affected part in our patients. Under general anesthesia, a total laminectomy was performed at the C1-C2 level. Stem cells were injected to the anterior part of the spinal cord. RESULTS: During the follow-up of 1 year after stem cell implantation, nine patients became much better compared with their pre-operative status, confirmed by electro neuro myography (ENMG). One patient was stable without any decline or improvement in his status. Three patients died 1.5, 2 and 9 months, respectively, after stem cell therapy as a result of lung infection and myocardial infarction (MI). DISCUSSION: These results show that stem cell therapy is a safe, effective and promising treatment for ALS patients.

Treatment of chronic spinal cord injured patients with autologous bone marrow-derived hematopoietic stem cell transplantation: 1-year follow-up.

BACKGROUND: Transplanted bone marrow (BM) cells have been found to improve neurologic disease in central nervous system (CNS) injury models by generating neural cells or myelin-producing cells. The results in treated patients and animal models suggest that BM cells could potentially be used as a therapy for spinal cord injury (SCI) patients. METHODS: Nine patients with chronic complete SCI with American Spinal Injury Association (ASIA) Impairment Scale (ASIA) grade A were included in this study. They were treated with autologous BM-derived hematopoietic progenitor stem cell transplantation without any serious complications. All patients completed the protocols successfully. RESULTS: Three weeks after the operation all patients' movements and sensations were improved. All patients had ASIA grade B or C after the operation. DISCUSSION: We used autologous hematopoietic progenitor stem cells in order to avoid the problems associated with immunologic rejection and graft-versus-host (GvH) reactions, which are frequently caused by allografts. The advantage of this type of cell therapy is that it is not associated with carcinogenesis, which sometimes occurs with embryogenic stem cell therapy. To evaluate the patients we used neurologic impairment scales (ASIA scores), pre- and post-operative Somato Sensorial Evoked Potential (SSEP) assessments and pre- and post-operative Magnetic Resonance Imaging (MRI). All the data showed that BM-derived autologous stem cell therapy is effective and safe for the treatment of chronic SCI.

Clustering of invasive Aspergillus ustus eye infections in a tertiary care hospital: a molecular epidemiologic study of an uncommon species.

Aspergillus infections are being increasingly recognized as an important cause of morbidity and blindness. We report here the first cluster of Aspergillus ustus endophthalmitis cases which occurred in a large tertiary care hospital during the period October 2003 to June 2004. In three of the cases, the patients required enucleation following cataract surgery, while the fourth involved a fatal infection in a pediatric patient hospitalized for osteopetrosis. Patient charts from the four cases were reviewed retrospectively and indicated that postoperative signs of fungal endophthalmitis developed in the patients 1-11 weeks after surgery. The molecular characterization of the isolates and their epidemiological relatedness were evaluated by Random Amplification of Polymorphic DNA (RAPD). A source investigation of this mini outbreak was performed by environmental sampling, but no isolates of A. ustus were recovered from these studies. All A. ustus strains isolated from three patients with fungal endophthalmitis had the same RAPD pattern suggesting a common source. The strain from the pediatric patient differed from the ophthalmic isolates in five electrophoretic loci. The latter was included solely as an outbreak, unrelated control to evaluate the discriminatory power of the molecular typing method employed in the analysis of the ophthalmic strains. These cases illustrate the potential for uncommon species like A. ustus to cause high morbidity and mortality in some clinical settings. Aspergillus ustus endophthalmitis is a serious and devastating complication of ocular surgery. It is unknown whether ongoing hospital construction may have contributed to this cluster of cases. Random amplification of polymorphic DNA may give valuable clues about the clonality of A. ustus strains.

Hepatitis B complicated focal segmental glomerulosclerosis.

After the initial report of membranous glomerulopathy due to hepatitis B virus infection by Combes et al, other glomerular diseases - but rarely focal segmental glomerulosclerosis (FSGS) association with HBV infection - have been reported. Herein we present an 8-year-old boy with chronic HBV infection complicated FSGS. The patient was initially regarded as idiopathic FSGS and started on an immunosuppressive schedule. The elevation of liver transaminases in the course of the therapy revealed the immunotolerated perinatal HBV infection. It was considered that immunosuppressive agents have induced viral replication. The treatment was changed to lamivudine alone. The nephrotic syndrome has already been improved with the seroconversion of anti-HBeAg and reduced liver functional tests by the tenth month of the treatment. This case is peculiar for the seldom association of FSGS with chronic HBV infection and treatment modality particularly for the countries where this viral infection is endemic.

Is there a relationship between childhood Helicobacter pylori infection and iron deficiency anemia?

An association between Helicobacter pylori infection and iron deficiency anemia has been reported in children, and it has been proposed that H. pylori infection needs to be eradicated to treat absolutely iron deficiency anemia (IDA). We investigated whether there was any correlation between H. pylori infection and iron deficiency (ID) and IDA in children, and whether the eradication of H. pylori infection without iron treatment would lead to the resolution of ID. Hemoglobin and ferritin levels, H. pylori stool antigen test and (14)C urea breath test were measured in 140 children aged 6--16 years (median 9.5 years). Children with H. pylori infection were divided into three groups on the basis of hemoglobin, mean corpuscular volume (MCV), and serum ferritin levels: groups of IDA, ID, and control. All the children received anti-H. pylori combination therapy consisting of amoxicillin, clarithromycin, and lansoprazole. Hemoglobin and MCV values rose significantly compared with baseline values after H. pylori eradication without iron supplementation in children with IDA (p=0.002 and p=0.003, respectively). Ferritin values increased significantly after H. pylori eradication in children with ID (p<0.001). We conclude that complete recovery of ID and IDA can be achieved with H. pylori eradication without iron supplementation in children with H. pylori infection.

Hereditary multiple exostoses and acute myeloid leukemia: an unusual association.

Hereditary multiple exostoses (HME) is an autosomal dominant disorder characterized by the presence of multiple exostoses. Three genetic loci have been identified, of which two (EXT1 and EXT2) have tumor suppressor activity. HME greatly increases the risk to develop sarcoma in the dysplastic tissue. The authors report an 8-year-old girl with HME who developed acute myeloblastic leukemia.

Brucellosis transmitted by bone marrow transplantation.

We report a unique case of brucellosis transmitted by BMT. An 8-year-old boy with the diagnosis of Fanconi's anemia received an allogeneic BMT from his HLA-identical sibling. Routine culture from the infused marrow suspension grew Brucella abortus on day +4 post BMT. Spiking fevers occurred on days +2 and +16. The first febrile episode responded to broad-spectrum antibiotic therapy. However, the second episode did not. B. abortus was isolated from blood cultures taken during the second febrile episode. The Brucella agglutination titer was negative. Antibiotic therapy with oral doxycycline and i.v. gentamycin was successful with no recurrence of infection during 13 months of follow-up. The donor's blood culture was also positive for B. abortus and Brucella antibodies were detectable at 1:320 titer when he presented with fever and hepatosplenomegaly on day +32. We emphasize the need to consider brucellosis in patients undergoing BMT. We suggest that donor and recipient be evaluated for brucellosis especially in countries where the incidence of this infection is relatively high.

Malignant fibrous histiocytoma in a child. A case report and review of the literature.

Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma of late adult file. It is extremely rare in children, though, and its existence in the pediatric population remains controversial. Although the most common site of tumor in children is the extremities, which is similar to findings of adults' series, different sites have been reported in children. Because of the rarity of this tumor in childhood, the approach to treatment of MFH is based primarily on the experience with adults. We present the clinical and pathologic features of an eight-year-old boy with MFH located on his left retroperitoneum and also review the literature.

Effect of iron therapy on the whole blood platelet aggregation in infants with iron deficiency anemia.

This study was performed to investigate the platelet aggregation alterations in whole blood samples of infants with iron deficiency anemia. Platelet aggregation induced by various concentrations of adenosine diphosphate (ADP) and collagen was studied with impedance aggregometry in 25 patients before and after oral iron therapy and in 12 children of the control group. The posttreatment mean maximum aggregation values were significantly higher (p<0.01) and the posttreatment mean aggregation times were significantly lower (p<0.01) in the study group at all concentrations of ADP and collagen. The aggregation time and maximum aggregation values revealed no significant difference except for the maximum aggregation value at 5 microM ADP (p<0.05) between the study group after therapy and the control group. The differences between the pretreatment and posttreatment mean platelet counts and mean platelet volume values in the study group were statistically significant (p<0.01), whereas those values in the study group after therapy and in the control group were not significantly different. We conclude that iron deficiency anemia in infants, even without clinically meaningful platelet abnormality, may cause dysfunction of the ex vivo whole blood platelet aggregation, and can be reversed by iron therapy. Further studies should be carried out at the enzymatic level to determine whether this platelet aggregation dysfunction in iron deficiency anemia is due to a deficiency in the activation of iron-containing enzymes.

Comparison of the efficacy and side-effects of ondansetron and metoclopramide-diphenhydramine administered to control nausea and vomiting in children treated with antineoplastic chemotherapy: a prospective randomized study.

UNLABELLED: Nausea and vomiting following antineoplastic therapy in patients receiving chemotherapy remains a problem. To prevent nausea and vomiting due to antineoplastic therapy, many types of drugs have been used. Ondansetron and the combination metoclopramide-diphenhydramine have been widely used in children. In this prospective randomized study these drugs were compared both for their efficacy and side-effects in children treated with antineoplastic chemotherapy (with and without cisplatin) the number of chemotherapy courses being equal in both groups. Ondansetron gave complete anti-emetic cover in five of nine courses in patients treated with cisplatin. Metoclopramide-diphenhydramine gave complete anti-emetic cover in one out of nine courses, and 17 out of 23 courses in patients treated without cisplatin. Metoclopramide-diphenhydramine produced side effects in nine courses whereas ondansetron produced side-effects in three courses. CONCLUSION: Ondansetron appeared to be superior to metoclopramide-diphenhydramine in the control of emesis induced by chemotherapy regimens containing cisplatin. The results of the present prospective randomized study indicate that ondansetron is a useful anti-emetic in the treatment of chemotherapy-induced emesis.

Mobilization of peripheral blood progenitor cells using 16 versus 10 mg/kg/d G-CSF in children with malignancies.

Administration of hematopoietic growth factors, with or without chemotherapy, can augment progenitor cell numbers available for collection. The dose of granulocyte colony stimulating factor (G-CSF) used for mobilization of peripheral blood progenitor cells (PBPC) is controversial, and doses between 5 and 32 microg/kg/d have been reported in adults. In order to determine the dose-response effect for G-CSF in mobilizing PBPC in children, we randomized 30 children with malignancies to receive either 16 or 10 microg/kg/d subcutaneously starting on the day after the disease-oriented chemotherapy regimen and continuing until the completion of leukapheresis. Leukapheresis commenced after threshold WBC > 1 x 10(9)/L was achieved and continued until 10 x 10(6) CD34+ cells/kg were obtained or for 6 procedures. Both treatment groups achieved an adequate yield of CD34+ cells with an average of 4 leukapheresis procedures. The numbers of CD34+ cells/kg were 8.3 x 10(6) and 11.7 x 10(6) in patients receiving 16 and 10 microg/kg/d doses of G-CSF, respectively, or 2.1 x 10(6) and 3.7 x 10(6) cells/kg per leukapheresis. The levels of CD34+ cells in peripheral blood had a wide interindividual variation, and were not significantly different after 16 or 10 microg/kg doses of daily G-CSF. We conclude that there is no advantage to using 16 microg/kg/d of G-CSF post-chemotherapy for PBPC mobilization in children.

Klippel-Trenaunay-Weber syndrome with hemimegalencephaly. Report of a case.

A case of Klippel-Trenaunay-Weber Syndrome (KTWS) in a 2.5-year-old girl with congenital hemihypertrophy, nevus flammeus and liver hemangioma is presented. In addition, this report describes the rare association of hemimegalencephaly with KTWS.

The normalization period of platelet aggregation in newborns.

This study was performed to investigate the normalization period of the transient platelet dysfunction of newborns. A total of 43 healthy newborns of healthy mothers who had received no medication for at least 14 days prior to delivery were included in the study. Venous blood samples of 44 healthy volunteer adults were used as control. Platelet aggregation study was performed in whole blood by impedance aggregometry. Collagen or ADP was used as the aggregating agent. In the platelet aggregation studies using collagen, maximum aggregation values in the first three days of life were lower than those of adults (p < 0.001). These lower values were improved and reached adult values between the 5th and 9th day of life. Lower maximum aggregation values were observed in newborns in comparison with those of adults when ADP was used, but the difference was not significant except for 5 microM concentration of ADP. There was no significant difference between the aggregation time of the collagen and ADP groups (p > 0.05). In conclusion, the platelet responses to ADP and collagen were increased in newborns as the age progressed and reached normal levels between 5th and 9th day of life. If platelet dysfunction does exist after the 10th day of life, this finding may be due to either simple prolongation of the physiological phenomenon or platelet disorders.