Lead poisoning in an electrician: a bad substitute for a bad habit.

An electrician presented with a four-month history of unexplained abdominal pain and constipation, which had prompted four hospital admissions and numerous investigations. Blood-film results suggested lead poisoning, and an occupational history revealed that he had chewed about a metre of electrical cable (which contains lead) daily for 10 years as a substitute for smoking.

A large beta-thalassemia deletion in a family of Indonesian-Malay descent.

The partial molecular characterization of a large deletion present in two members of an Indonesian-Malay family with beta-thalassemia trait is described. Polymerase chain reaction and sequencing analyses of the breakpoint identified a sequence which has previously been described in patients with the 45 kb Filipino beta 0-thalassemia deletion, i.e. a 5' breakpoint at position -4279 nucleotides 5' from the Cap site of the beta-globin gene. The 3' breakpoint is located in an L1 family of repetitive sequences at an unknown distance from the beta-globin gene. The hematological and hemoglobin data of the patients with this beta 0-thalassemia deletion further supports the concept that the unusually high Hb A2 levels are unique to deletions removing the 5' beta-globin gene region, and points to the importance of the 3' junction sequences for the regulation of Hb F levels in patients with deletional defects of the beta-globin gene cluster.

Rapid detection of deletions causing delta beta thalassemia and hereditary persistence of fetal hemoglobin by enzymatic amplification.

A considerable number of deletions of variable size and position that involve the beta-globin gene complex on chromosome 11 are associated with the clinical entities of hereditary persistence of fetal hemoglobin (HPFH) and delta beta thalassemia. Specific deletions appear to be associated with consistent phenotypes and some are known to be recurrent. To facilitate the molecular diagnosis of uncharacterized patients with HPFH and delta beta thalassemia, oligonucleotide primers have been designed to enzymatically amplify deletion-specific products for nine known deletions, which include those responsible for HPFH-1, HPFH-2, HPFH-3, Spanish (delta beta)zero thalassemia, hemoglobin (Hb) Lepore, Sicilian (delta beta)zero thalassemia, Chinese G gamma(A gamma delta beta)zero thalassemia, Asian-Indian inversion-deletion G gamma(A gamma delta beta)zero thalassemia, and Turkish inversion-deletion (delta beta)zero thalassemia. Using this approach, we have successfully characterized the molecular basis for delta beta thalassemia in 23 individuals from 16 families of diverse ethnic origins. Thirteen individuals from this group were shown to be heterozygous for the 13.4-kb Sicilian deletion, two were heterozygous for the 100-kb Chinese G gamma(A gamma delta beta)zero deletion, four were heterozygous for the Turkish form of inversion-deletion delta beta thalassemia, and three were heterozygous for the Asian-Indian form of inversion-deletion G gamma(A gamma delta beta)zero thalassemia. One Vietnamese subject was heterozygous for a 12.6-kb deletion, which we have fully characterized at the molecular level. Sequence analysis of the breakpoint regions of the Chinese deletion and the Turkish rearrangement indicates that, in each case, the mutation is likely to have arisen from a single origin. This hypothesis is supported by the evident geographical clustering of the various deletions described here.

A novel deletion of approximately 27 kb including the beta-globin gene and the locus control region 3'HS-1 regulatory sequence: beta zero-thalassemia or hereditary persistence of fetal hemoglobin?

A novel deletion of approximately 27 kb with the 5' breakpoint 1.5 to 2.2 kb upstream of the beta-globin gene, and the 3' breakpoint approximately 24 kb downstream of the beta-globin gene, has been found in five members of two families from Southeast Asia (Vietnam and Cambodia). Six members of another family from China, previously reported from our laboratory, have also been shown to carry this deletion. The patients presented with mild hypochromia and microcytosis, a hemoglobin (Hb) A2 level of approximately 4.0%, and a markedly increased, heterocellularly distributed, Hb F level (14.0 to 26.0%). In vitro globin-chain synthesis showed a mild imbalance with appreciable gamma-chain compensation (alpha/beta + gamma ratio of 1.46). The 3' end of this deletion includes the 3'HS-1, and we hypothesize that removal of this region results in the loss of its gamma-globin gene-silencing effect, which causes a markedly elevated Hb F level with a modest increase in Hb A2 levels, unlike the situation in other deletional beta zero-thalassemias. The possible influence of particular sequence variations in the locus control region 5'HS-2 and the G gamma promoter, present on the chromosome with this deletion, on the overall gamma-globin gene should also be considered.

Acquired haemoglobin H disease, complicating a myeloproliferative syndrome: a case report.

A case of acquired haemoglobin H disease in association with a myeloproliferative disorder is described. Severe haemolysis with hypochromic microcytic anaemia was present. Haemoglobin H formed 18% of the circulating haemoglobin and 60% of the red cells showed multiple inclusions on incubation with brilliant cresyl blue. Blood film and absolute red cell values from a previous unrelated illness were normal, proving the acquired nature of the haemoglobin abnormality. Alpha/beta chain synthesis was measured in vitro and the degree of imbalance (alpha/beta ratio 0.39) was similar to that seen in the inborn thalassaemic disorder. A small proportion of red cells showed i-antigen reactivity but their haemoglobin H content was no different from the majority of cells which were l-antigen positive.

Bone marrow metastases in disseminated alveolar rhabdomyosarcoma: case report with ultrastructural study and review.

A case of desseminated alveolar rhabdomyosarcoma in an 18-year-old male with leuco-erythroblastic anaemia is described. Numerous bizarre malignant cells, including frequent multinucleated giant cells, were seen in bone marrow aspirates, and osteolytic lesions appeared late in the clinical course. The primary site of the neoplasm remained undertermined during life and also at necropsy, which revealed minute pulmonary metastases and extensive lymph nodal, pleural and skeletal deposits. The diagnosis was confirmed on necropsy tissue by ultrastructural examination which demonstrated numerous thin (5 nm) and thick (15 nm) intracytoplasmic filaments in tumour cells, sometimes organized in bundles; scattered dense Z-band-like bodies, and rod-shaped structures were also seen. The fine structure of the rhabdomyosarcoma in the present case is compared with previous ultrastructural studies. Elongated, thick intracytoplasmic filaments whose diameter corresponds to that of myosin myofilaments are strong evidence for rhabdomyoblastic differentiation and are considered to be the sine qua non of a positive electron microscopic diagnosis of rhabdomyosarcoma. Orgaized bundles of filaments and Z-band-like dense bodies are usually present, and rod-shaped structures are found infrequently, but none of these are necessary for the ultrastructural diagnosis.

Extraction of serum vitamin B12 for radio-isotopic and Lactobacillus leichmannii assay.

The protein precipitates discarded during the extraction process of the Lactobacillus leichmannii vitamin B12 assay have been shown to contain significant amounts of vitamin B12. This loss of vitamin B12 provide a satisfactory explanation for many of the descrepancies between the serum vitamin B12 values obtained by the L. leichmannii method and the radio-isotopic method of Raven et al (1969). It is possible to produce lower results by the method of Raven et al (1969)by incorporating into that method the L. leichmannii extraction process; it is also possible to produce higher results by the L. leichmannii method using a papain extraction process.

Experience with a commercial kit for the radioisotopic assay of vitamin B12 in serum: the Phadebas B12 test.

The first commercial kit for the radioisotopic assay of vitamin B(12) in serum-the Phadebas B(12) Test produced higher values than the radioisotopic method of Raven, Robson, Walker, and Barkham (1969) and the Lactobacillus leichmannii microbiological assay. Its normal range was 300-1100 pg/ml and its reproducibility was similar to that of the other radioisotopic method. It should be possible to lower the results obtained by the Phadebas method by modifying its standard curve and to reduce the time taken for the assay by shortening its incubation period.

Improved method for measuring vitamin B12 in serum using intrinsic factor, 57CoB12, and coated charcoal.

An improved and simplified method is described for the measurement of vitamin B(12) in serum using intrinsic factor, (57)CoB(12), and coated charcoal. The extraction of serum in the presence of cyanide and the incorporation of B(12)-deficient serum into the intrinsic factor control has increased the accuracy of the method for both sera and crystalline B(12) solutions. There are interesting differences between the results obtained for some sera by the isotope and L. leichmannii methods and the reasons for these differences are discussed.