Clinical and experimental study of shengxue syrup in treating chronic aplastic anemia

The Shengxue Syrup (SXS) composed of Chinese medicinal herbs for invigorating the function of Spleen and resplenishing the Kidney was used in treating 115 chronic aplastic anemia patients. The SXS group consisted of 67 patients. After the median 20 months treatment the total effective rate (TER) was 97.0%. The other group was SXS + testosterone group consisted of 48 patients. After median 17.5 month treatment the TER was 95.8%. The difference of TER between two groups was insignificant. The result of animal experiment showed that SXS could markedly enhance the hematopoietic stem cells as well as progenitor cells proliferation of bone marrow in mice.     

Autoimmunity and its treatment in aplastic anemia

A pilot survey of men aged 35 and over in Buenos Aires indicated that many had one or more risk factors for chronic diseases. A low response rate hampered the investigation: on average it proved necessary to visit several homes in order to obtain one interview. Furthermore, at the cost of US$ 10 incurred per interview, large prospective investigations would be precluded in most developing countries, but case-control studies assessing tobacco use and other risk factors retrospectively would be a good alternative.     

Decreased rejection and improved survival of first and second marrow transplants for severe aplastic anemia (a 26-year retrospective analysis)

Between 1970 and 1996, 333 patients with severe aplastic anemia underwent HLA-matched related marrow transplant after conditioning with cyclophosphamide (CY). Thirty-five percent of patients transplanted between 1970 and 1976 (group 1), 12% of those transplanted between 1977 and 1981 (group 2), and 9% of patients transplanted between 1982 and 1997 (group 3) had graft rejection. Graft rejection occurred later among group 3 patients (median, 180 days) than among those in groups 1 and 2 (medians, 28 and 47 days, respectively; P < .001 group 3 v 2). In group 3, 92% of rejecting patients underwent a second transplant, compared with 78% and 77% in groups 1 and 2, respectively. Group 1 patients received various conditioning regimens before second transplant, whereas most patients of groups 2 and 3 received CY combined with antithymocyte globulin (ATG). Graft-versus-host disease (GVHD) prophylaxis after second transplant consisted of methotrexate (MTX) for all group 1 and 2 patients, whereas group 3 patients received MTX combined with cyclosporine (CSP). Over the three time periods studied, first graft rejection decreased from 35% to 9%, and the proportion of rejecting patients undergoing second transplants increased from 77% to 92%. The 10-year probability of survival after second transplants increased from 5% to 83%. Multivariate analysis showed MTX/CSP GVHD prophylaxis to be a significant factor accounting for the increase in patient survival after second transplant.     

Severe aplastic anemia as a complication of treatment with metizol

Aplastic anemia is the rare hematologic complication of the antithyroid medication. We present here the case of 39-years old female who was treated with Thiamazole due to Graves disease. This and the others cases cited in the literature indicate that antithyroid drugs-induced aplastic anemia is characterised by severe clinical status and profound marrow hypoplasia or aplasia but good prognosis with short term recovering.     

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.     

Aplastic anemia or aplastic preleukemic syndrome?

The incidence of aplastic anemia appears to be relatively high in some parts of the world, including Pakistan. Since some of the etiological factors are shared by aplastic anemia and the preleukemic syndrome, there is a strong possibility that a proportion of cases of aplastic anemia may in fact be preleukemia. The study of chromosomes offers a relatively easy method of detecting cases of preleukemia, because some chromosomal abnormalities are frequently observed in this condition. Chromosomal studies were carried out in peripheral blood cell cultures of 31 patients with otherwise typical aplastic anemia. Chromosomal abnormalities were detected in 7 (22.5%) cases. The most common chromosomal abnormality detected was trisomy 8, seen in four cases. Other abnormalities detected were 22q-, t(14;22) and t(15;21), in one case each. These abnormalities have been found to be associated with AML, MDS, ALL, and NHL as well. We hypothesize that a proportion of cases of otherwise typical aplastic anemia may in fact be due to a leukemic process in evolution.     

Paroxysmal nocturnal hemoglobinuria and its association with aplastic anemia

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder of haematopoiesis. Clinically it is characterized by intravascular haemolysis, venous thrombosis and often by bone marrow hypoplasia. Haemolysis and thrombosis develop as a consequence of deficiency of several proteins on the cell membrane of the affected clone of blood elements. This is caused by somatic mutations in the PIG-A gene, which encodes an enzyme involved in the biosynthesis of glycosylphosphatidylinositol (GPI) anchor. Spectrum of mutations in the PIG-A gene is different to that observed in other genes. The mutations are mainly small deletions and insertions causing frameshift; large deletions are rare. Recently, however, a 88 base pairs direct tandem repeat insertion has been reported in a patient with PNH developed on the background of aplastic anaemia (AA). The peculiar pattern of the PIG-A gene mutations and the finding that more than one mutated clone is commonly present in patients with PNH might suggest that some form of hypermutability, caused by decreased DNA stability, deficient repair or increased generation of mutagens, might underline PNH. As most mutations cause cell death, it would explain the hypoplastic nature of the disorder and its association with AA. Other models of pathogenesis of PNH are also discussed.     

Granulomatous hepatitis: a retrospective study

51 cases of granulomatous hepatitis were seen among 1234 liver biopsies over a 10 year period. Tuberculosis was the commonest cause seen in 55 percent of cases. Other causes included leprosy, sarcoidosis, histoplasmosis, brucellosis, amoebic liver abscess, lymphoma and malignant granuloma. 12 percent of cases remained undiagnosed. Clinically these patients presented with pyrexia and hepatosplenomegaly. Jaundice was uncommon. Many showed elevated alkaline phosphatase levels, anaemia and raised ESR Granulomatous hepatitis of unknown aetiology with FUO was seen in 6 percent cases only.     

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.     

Immune suppression therapy in aplastic anemia: influencing factors on response and survival

Calpains are intracellular cysteine proteases activated in a Ca(2+)-dependent manner. Previously, we found that the differentiation of K562 cells induced by 4 beta-phorbol 12-myristate 13-acetate treatment is accompanied by an increase in m-calpain levels and, at the same time, m-calpain becomes localized on the inside of plasma membranes, coated pits, and coated vesicles [Nakamura, M., Mori, M., Morishita, Y., Mori, S. & Kawashima, S. (1992) Exp. Cell Res. 200, 513-522]. We also reported that mu-calpain plays an essential role in morphological changes and membrane fusion of erythrocytes through the degradation of spectrin, a lining protein [Hayashi, M., Saito, Y. & Kawashima, S. (1992) Biochim. Biophys. Res. Commun. 182, 939-946]. Thus, calpains are implicated in endocytosis and/or exocytosis, processes stimulated by Ca2+ and involving intracellular membrane fusion. In this study, we report the biochemical characterization of calpains as components of purified coated vesicles from bovine brain. It was found by Western-blot analysis and chemical cross-linking of proteins that calpains are bound to the membranes of coated vesicles, and not to the coats. The binding of m-calpain to vesicles is Ca(2+)-dependent, while that of mu-calpain is less dependent on the presence of Ca2+. We also identified substrate proteins for calpains in coated vesicles. Upon activation of endogenous calpains, component proteins of coated vesicles such as the clathrin light chain, tubulins, and adaptins, but not the clathrin heavy chain, are highly sensitive to calpain digestion. In the case of exogenously added calpains, low concentrations degraded the same protein components. The degradation pattern differs slightly between added mu-calpain and m-calpain. These results strongly suggest that calpains are involved in the formation of coated vesicles and/or vesicle fusion to endosomes.