Congenital dyserythropoietic anemia,type 1, in a polynesian patient: response to interferon alpha2b

The authors attempted to assess the utility of interferon alpha2b treatment in a Polynesian girl with a relatively severe form of congenital dyserythropoietic anemia, type 1. The diagnosis was established using routine hematologic and biochemical tests, light and electron microscopy, and electrophoresis of red cell membrane proteins. Response to the treatment was monitored using the blood count and reticulocyte count. The patient was age 14 when interferon treatment was started. Previously, she had been partially dependent on transfusions, and gallstones and iron overload had developed. The dose of interferon alpha2b was initially 3 x 10 units three times a week for 1 year and 3 x 10 units twice a week thereafter. On this treatment, hemoglobin and reticulocytes increased and transfusions became unnecessary. In keeping with a few previous reports, interferon alpha2b proved to be effective in congenital dyserythropoietic anemia, type 1. The patient became transfusion-independent. More cases need to be studied to optimize the dosage of interferon alpha2b and determine how long the treatment can be tolerated.     

Anorexia nervosa in early adolescence in Sri Lanka

We report four cases of anorexia nervosa (AN) seen over a period of 5 months in the psychiatry unit of a general hospital. The report is unusual because two of the patients were male, all were between 13 and 15 years of age and AN is thought to be rare in Sri Lanka. All four patients had features typical of AN. There are implications for clinical practice in Sri Lanka if the prevalence of AN is rising because all these patients presented to psychiatrists late in their illness, some in an advanced state of weight loss.     

Clinical and molecular stratification of disease risk in medulloblastoma

The accurate assessment of disease risk among children with medulloblastoma remains a major challenge to the field of paediatric neuro-oncology. In the current study we investigated the capacity of molecular abnormalities to increase the accuracy of disease risk stratification above that afforded by clinical staging alone. 41 primary medulloblastoma tumour samples were analysed for ErbB2 receptor expression using immunohistochemistry, and for aberrations of chromosome 17 and amplification of the MYC oncogene using fluorescence in situ hybridisation. The ErbB2 receptor and deletion of 17p were detected in 80% and 49% of tumours, respectively. 17p loss occurred either in isolation (20%), or in association with gain of 17q (29%), compatible with an isochromosome of 17q. Amplification of MYC was detected in only 2 tumours. Significant prognostic factors included, 'metastatic disease' (P = 0.0006), 'sub-total tumour resection' (P = 0.007), 'high ErbB2 receptor expression' (P = 0.003) and 'isolated 17p loss' (P = 0.003). Combined analysis of clinical and molecular factors enabled greater resolution of disease risk than clinical factors alone, identifying a sub-population of patients with particularly favourable disease outcome. These data support the hypothesis that a combination of clinical and molecular factors may afford a more reliable means of assigning disease risk in patients with medulloblastoma, thereby providing a more accurate basis for targeting therapy in children with this disease.     

Congenital dyserythropoietic anemias

The congenital dyserythropoietic anemias (CDAs) are an uncommon and heterogeneous group of disorders characterized by markedly ineffective erythropoiesis and, usually, striking dysplastic changes in erythroblasts. Each of the three originally described forms, designated CDA types I to III, is defined by the presence of distinctive morphologic (including ultrastructural) abnormalities in erythroblasts. CDA type II is also characterized by a marked reduction in polylactosamine structures associated with the erythrocyte membrane glycoprotein, band 3 (detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis), and, usually, a positive result on the acidified serum lysis test. The course of CDA is often complicated by cholelithiasis. Even patients who have not had transfusions sometimes develop substantial iron overload. Recent studies have extended our knowledge on the clinical manifestations of CDA types I and III and have revealed the existence of forms of CDA distinct from types I to III. Information is now available on the chromosomal localization of the genes involved in CDA types I and II and in the Swedish cases of CDA type III. A few patients with CDA type I have been treated with interferon-alpha2, with a good response.     

Foot Protective System : A Boon to Demining Soldiers

Background

A significant number of soldiers suffer serious injuries or die in the process of demining and a protective device is necessary in such operations.

Methods

All the patients involved in demining operations using the foot protection devices in last one year were analysed.

Results

We received 35 patients, of which only five had limb injuries and 30 had eye injuries. Of the five, three had closed calcaneal fractures and two contusion of foot. No fatality, amputation or compound fracture occured.

Conclusion

Early results after the use of this device during demining operations are encouraging.Key Words: Mine blast injury, Demining, Spider boot     

A normal β-globin allele as a modifier gene ameliorating the severity of α-thalassemia in mice

Thalassemia is a heritable human anemia caused by a variety of mutations that affect expression of the alpha- or the beta-chain of hemoglobin. The expressivity of the phenotype is likely to be influenced by unlinked modifying genes. Indeed, by using a mouse model of alpha-thalassemia, we find that its phenotype is strongly influenced by the genetic background in which the alpha-thalassemia mutation resides [129(sv/ev)/129(sv/ev) (severe) or 129(sv/ev)/C57BL/6 (mild)]. Linkage mapping indicates that the modifying gene is very tightly linked to the beta-globin locus (Lod score = 13.3). Furthermore, the severity of the phenotype correlates with the size of beta-chain-containing inclusion bodies that accumulate in red blood cells and likely accelerate their destruction. The beta-major globin chains encoded by the two strains differ by three amino acids, one of which is a glycine-to-cysteine substitution at position 13. The Cys-13 should be available for interchain disulfide bridging and consequent aggregation between excess beta-chains. This normal polymorphic variation between murine beta-globin chains could account for the modifying action of the unlinked beta-globin locus. Here, the variation in severity of the phenotype would not depend on a change in the ratio between alpha- and beta-chains but on the chemical nature of the normal beta-chain, which is in excess. This work also indicates that modifying genes can be normal variants that-absent an apparent physiologic rationale-may be difficult to identify on the basis of structure alone.     

Differences in the Nature and Kinetics of the Ethanol-related Circulating Cytotoxic Proteins in Normal Subjects and Patients with Alcohol-induced Cirrhosis

The kinetics and nature of the nondialyzable cytotoxic activity which appeared in the serum after the consumption of 1.2 g ethyl alcohol per kilogram body weight over 45 min was studied in six healthy volunteers and eight patients with histologically proven alcohol-related cirrhosis of the liver. Whereas the cytotoxic activity in the dialyzed serum showed a single peak with a maximum value 8 hr after the start of ethanol consumption in the healthy volunteers, it showed two peaks with maximum values at 2 and 8 hr in the patients with cirrhosis. Studies of the fractions obtained by Sephacryl-S-300 gel filtration of the 2-hr postalcohol serum samples revealed substantial cytotoxic activity in the fractions containing both the albumin peak and the IgG peak in the patients with cirrhosis and only in the fractions containing the albumin peak in the healthy volunteers. Experiments with pure IgG preparations obtained from prealcohol and 2-hr postalcohol sera by chromatography on Q-Sepharose Fast Flow anion-exchange resin showed considerable cytotoxic activity in the preparations from the patients with cirrhosis and little or no cytotoxic activity in those from the healthy volunteers. Thus, the early peak of the biphasic serum cytotoxicity curve seen after ethanol consumption by patients with cirrhosis appeared to be caused by the development of a substantial cytotoxic activity in the IgG molecules during the first 2 hr.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pneumothorax preceding pulmonary blastoma in a child

Serial plain radiographic, ultrasound and CT findings of an unusual case of pulmonary blastoma are described with a review of the literature.