Stable mixed chimerism without relapse after related allogeneic umbilical cord blood transplantation in a child with severe aplastic anemia

Umbilical cord blood (UCB) cells from HLA-matched donors are used as an alternative to bone marrow for allogeneic transplantation and reports of successful UCB transplantation in patients with severe aplastic anemia (SAA) are scarce. SAA was discovered in a 4-year-old girl in February 1990. Transfusion support started in August 1990 and standard treatments were unsuccessful. The birth of an HLA-compatible brother in October 1993 permitted the cryopreservation of UCB. In December 1994 UCB transplantation was decided upon. No toxicity occurred. G-CSF was started at day 28. WBC and PMN reached 0.5 x 10(9)/l at days 33 and 37. RBC and platelet transfusion independence were reached at days 50 and 52. Mixed chimerism was demonstrated in blood cells at 1.5, 4 and 6 months after UCBT by molecular biology (VNTR). FISH studies yielded similar results at 15 and 18 months. Twenty months after UCBT, molecular biology showed full donor chimerism. Clinical follow-up (last follow-up: 32 months post transplant) is unremarkable. We suggest that CY and ATG may be a suitable regimen for related HLA-compatible UCBT in patients with SAA. Residual recipient cells can disappear even very late after UCBT, permitting the establishment of complete donor chimerism.     

Structural changes in the gastric foveolar epithelium in Helicobacter pylori-positive gastritis revealed by keratin immunohistochemistry

To clarify structural changes in the gastric foveolar epithelium in Helicobacter pylori (Hp)-positive gastritis, the expression rates of keratins 8, 18, 19, and 20 were assessed immunohistochemically in normal tissue and chronic gastritis. In normal tissue, keratin 8 was found in 100% of the cells. Staining for keratins 18 and 19 was abundantly positive. Keratin 20 was not expressed in the deep foveolae, but present in the upper foveolae and on the tips. No differences were found between the antrum and the body. In chronic gastritis, both Hp-positive and -negative, keratins 8, 18, and 19 were expressed comparably to normal tissue. Keratin 20 expression in the antrum was significantly lower in Hp-positive compared with Hp-negative gastritis (P < .05) and normal tissue (P < .05). In the body, staining for keratin 20 did not differ significantly between all groups. The difference in keratin 20 expression between the antrum and the body in Hp-positive gastritis was significant (P < .05). After successful eradication, staining for keratin 20 in the antrum normalized within 6 months (P < .05). These findings indicate structural changes in the gastric foveolar epithelium in Hp-positive gastritis. They predominantly include the antral region and show full reversibility after eradication.     

Bacillus cereus septicemia in a patient with severe aplastic anemia

A 78-year-old female was admitted with complaints of malaise and fatigue in the legs. The patient was diagnosed as severe aplastic anemia and treatment was started with metenolone and steroid pulse therapy. Administration of antibiotics and granulocyte-colony stimulating factor which led to a resolution of the high fever. About four months after admission, the patient developed vomiting and abdominal pain with a spiking fever. The next day after suddenly losing consciousness, she died. B. cereus was isolated from blood cultures. Autopsy specimens of the liver, cardiac muscle and lung showed changes due to B. cereus. This pathogen is widely distributed in nature. We should not overlook B. cereus as a contamination, but rather should consider it a potential pathogen in immunocompromised hosts, when it is isolated from blood cultures.     

Encephaloduroarterio-synangiosis in a child with sickle cell anemia and moyamoya disease

We report a black girl with sickle cell anemia. On prophylactic exchange transfusion protocol, she experienced cerebrovascular accidents at 3 and 3.5 years of age, both associated with transient right hemiparesis. At 7.5 years of age, she presented with a partial motor seizure and a left hemiparesis. A cerebral angiogram demonstrated stenosis at the origins of both middle and anterior cerebral arteries bilaterally with extensive basal collateralization. She underwent uncomplicated bilateral encephaloduroarteriosynangiosis (EDAS) procedures using both superficial temporal arteries. At age 9 years, the patient presented with a severe headache and tunnel vision secondary to a stenosis of both posterior cerebral arteries. She underwent bilateral EDAS procedures using both occipital arteries. No complication was encountered. Postoperative cerebral angiogram demonstrated impressive neovascularity at the sites of all four EDAS procedures. Different treatment options of moyamoya disease are discussed.     

Cytogenetic abnormalities in patients with severe aplastic anemia

BACKGROUND: Cytogenetic abnormalities have been described in a few patients with otherwise typical severe aplastic anemia (SAA), and the possible clonal nature of this disease is a controversial issue. MATERIALS AND METHODS: Sixty-nine patients with acquired severe aplastic anemia underwent cytogenetic examination on bone marrow cells at the time of diagnosis (n = 34) and/or at least twice after immunosuppressive therapy (IS) (n = 35). RESULTS: We identified 2 major groups. Group A: 51 patients (74%) were normal and remained normal. Group B: 18 patients (26%) had at least one abnormal cytogenetic analysis. This second group could be further subdivided as follows: (B1) chromosomal abnormalities not present at first examination and acquired in the course of the disease (n = 7); (B2) clonal cytogenetic abnormalities present at first examination and persisting (n = 3); (B3) reversible cytogenetic abnormalities (n = 8). The most frequent abnormality was trisomy 8 (n = 8) followed by monosomy 7 (n = 2); 82% of patients are alive in group A and 61% in group B. Three patients developed acute leukemia, all from group B. This represents 4% of all patients or 17% of those with at least one abnormal cytogenetic test. CONCLUSIONS: Thus the majority of SAA patients have normal karyotypes in marrow cells at presentation and at follow-up. Patients with abnormal karyotypes exist and can be further subdivided into those with reversible and those with persistent abnormalities. The latter are at risk of developing myelodysplasia or acute leukemia.     

浅析134例小儿胃炎的治疗与护理

目的:探讨小儿胃炎的防治与护理疗效观察.方法:对本组全部134例小儿胃炎患者采用药物结合护理治疗.结果:134例患者中,治愈88例,显效38例,有效6例,无效2例,总有效率98.5%.结论:临床上除药物治疗外,护理也十分重要,本文134例患者通过药物治疗及护理人员的悉心护理,总有效率98.5%,取得了良好疗效,值得临床推广.     

Serum gastrin and atrophic gastritis in achlorhydric patients with and without pernicious anemia

Forty-two patients with pernicious anemia (PA) and 35 patients with achlorhydria but without PA were investigated by means of serum gastrin determination and estimation of circulating parietal cell and thyroidal autoantibodies. In 38 of the 77 patients, gastroscopic and histopathological examinations of the antral and corpus mucosa were performed. The patient groups were similar with regard to distribution of high and normal serum gastrin levels, the frequencey of autoantibodies and antrum-sparing atrophic gastritis. In the present selection of patients, therefore, the achlorhydria group was supposed to represent a precursor state of the group with PA. A minor proportion of patients with severe atrophic gastritis of the antrum as well as of the corpus mucosa was found in the two groups.     

Refractory anemia with severe dysplasia: clinical significance of morphological features in refractory anemia

Refractory anemia (RA) in myelodysplastic syndromes (MDS) are very heterogeneous diseases regarding their morphology, clinical features and survival. We proposed the new designations 'RA with severe dysplasia (RASD)' and 'RA with minimal dysplasia (RAminiD)'. In our criteria, RASD is considered present if a bone marrow (BM) examination shows Pseudo-Pelger-Huet anomalies of mature neutrophils > or =3% and/or micromegakaryocytes (mMgk) of megakaryocytes > or =10% in RA patients. RAminiD is defined as RA cases other than RASD. After the reclassification of 58 primary RA patients, the group was composed of 45 RAminiD and 13 RASD patients. The blast percentage in the BM and the frequency of cytogenetic abnormalities observed in the RASD patients were intermediate between those in the RAminiD and RAEB patients. The analysis of survival curves revealed differences among the three groups; the RASD patients had lower survival probabilities than those of the RAminiD group, and significantly higher probabilities than those of the RAEB group. (RAminiD vs RASD, P=0.06; RASD vs RAEB, P=0.004.) Our data indicate that in RA patients, RASD is a distinct subset of RA with an unfavorable clinical outcome.     

The role of splenectomy in treating severe aplastic anemia

A hypotensive effect of clonidine in non-narcotized intact and aorta baro-denervated rats is studied under conditions of minimization of stress actions (radiotelemetry) and under standard conditions of direct recording arterial pressure (AP). Direct AP recording is shown to determine an increase in background AP in baro-denervated rats, but not in control rats. An increase in background AP level under conditions of direct recording is not accompanied with decreasing hypotensive effect of clonidine in baro-denervated rats.     

Microangiopathic hemolytic anemia and thrombocytopenia in a child with atrial septal defect and pulmonary hypertension

We found that exposure to room temperature (RT/21 degrees C) causes apoptosis in HL-60 cells. Here we characterized RT-induced apoptosis in HL-60. After exposure to RT, apoptosis starts within 6 h and more than 80% of the cells underwent apoptosis within 20 h. All cells, however, were committed to apoptosis after 16 h and no viable cells could be recovered. The caspase-1 inhibitor (YVAD-CHO) effectively blocked apoptosis, whereas the caspase-3 inhibitor (DEVD-CHO) did not. About 20% of newly obtained early passage HL-60 cells (passage 10) also underwent apoptosis by RT treatment. These data suggest that some population in HL-60 which responds to RT with apoptosis became dominant during passaging.     

Cyclosporin-A in severe refractory anemia of myelofibrosis with myeloid metaplasia: a preliminary report

Loss of chromosomes is a recurrent event in cancer. Chromosome-10 losses occur with tumor progression and characterize advanced gliomas. This chromosome carries many genes involved in glucose metabolism. Hexokinase (HK) gene is located on chromosome-10. Hexokinase enzymatic activity is decreased in glioblastomas. Hexokinase enables glucose entry into glycolysis and is critical for these highly glycolytic tumors. These enzyme is either free in the cytosol or bound to the mitochondrial outer membrane. Disturbance of HK binding to mitochondria by lonidamine led to inhibition of cells and xenografted-glioma growth. Hexokinase bind to a mitochondrial porin which involved peripheral benzodiazepine receptors. Inhibition of HK and peripheral benzodiazepine receptors by lonidamine and diazepam led to synergistic antitumoral activity in xenografted gliomas. Co-inhibition of these two receptors will lead to a decrease in glycolysis, often elevated in these tumors, without modifying energetic metabolism of normal cells.     

Autologous marrow recovery following allogeneic marrow transplantation in a patient with severe aplastic anemia

A 45-year-old woman with severe idiopathic marrow failure was prepared for marrow transplantation by administration of cyclophosphamide (cy) 50 mg/kg on each of four successive days. She then received an intravenous infusion of 20 X 10(9) nucleated marrow cells from an HL-A matched and mixed lymphocyte culture (MLC) non-reactive sister. There was evidence for minimal marrow recovery in 1-2 months and a second marrow infusion was carried out 69 days after the first without additional immunosuppression. There was a continued slow recovery of peripheral blood counts with complete reconstitution of erythropoiesis, return of the white blood cell count to between 3 and 4000/mm3, with 50% granulocytes, and platelets to 60--70,000/mm3, 11 months after the initial grafting attempt. Red cell antigens and gamma globulin allotypes were of recipient type. The MLC and the indirect cell mediated lympholysis (CML) test became positive possibly indicating cellular sensitization to non HL-A antigens. This report of a patient with severe marrow failure documents autologous recovery of marrow function after receiving a large dose of cy and allogeneic marrow. The implications of this are discussed.     

Levamisole treatment of a child with severe aphthous stomatitis and neutropenia

The treatment of a 12-year-old girl with a lifelone history of recurrent infections and aphthous stomatitis is reported. A profound neutropenis, first noted at the age of 2 years, occurring at least every month was observed together with multiple mouth ulcers a sore throat and swelling of the jugular glands. Levamisole, originally described as an anthelmintic, has a beneficial effect on the symptoms of recurrent aphthous stomatitis. After levamisole treatment aphthous stomatitis was milder and in the 1-year follow-up period the patient was asymptomatic several times during a phase of obvious neutrophil depression. The child no longer complained of a sore throat with swelling of the jugular glands and the recurrent staphylococcal infections of the skin disappeared. After therapy a marked increase in monocytes at the moment of neutropenia was observed.     

Hematopoietic stem cell transplantation for severe aplastic anemia

Clara cell protein (CC16) is an endogenous anti-inflammatory agent. It is produced mainly in the respiratory and urogenital tracts. CC16 has been quantified in serum, but not in cerebrospinal fluid (CSF). The aim of this study was to examine CSF CC16 in relation to age, gender and serum CC16, and to examine CC16 levels in parturients. If CC16 levels are increased with age and during pregnancy, it may be responsible for the attenuation of inflammatory diseases such as multiple sclerosis during these conditions. CC16 was measured in CSF and serum taken just before Caesarean section (n=33) or just before an elective surgical procedure in females (n=52) or males (n=31). Fetal serum, amniotic fluid, and maternal urine were also sampled during Caesarean section. CC16 levels in CSF did not differ between parturients and an age and gender matched non-pregnant group, but was higher in male than in female patients. There was a significant and positive relationship between age and CSF CC16 levels and between serum and CSF CC16 levels. Fetal CC16 was significantly and positively correlated with amniotic fluid CC16. The present study suggests that CC16 found in CSF originates from passive diffusion from blood, and that CC16 found in amniotic fluid is derived from the fetal lung. During pregnancy, CC16 does not appear to contribute to alterations which occur in the progression of inflammatory disorders.     

Rapid detection of engraftment using T cell receptor gene polymorphism after allogeneic bone marrow transplantation in an alloimmunized child with severe aplastic anemia

A severely alloimmunized boy with aplastic anemia received an HLA-identical BMT from his brother. Despite intensive immunosuppression and large marrow dose, peripheral signs of engraftment occurred only late under G-CSF treatment. With leukocyte counts of < 0.5 x 10(9)/l, chimerism could be proven not only by oligonucleotide fingerprinting but also within 48 h by analysis of polymorphism in the TCR gene family. This rapid and sensitive method to detect engraftment before it became quantitatively evident was important for the clinical management of the patient, obviating the need to search for an alternative marrow donor.