958

amplified and completely methylated; and the AF sample from the female fetus also carried a fragile X chromosome that was amplified and completely methylated. The amplification was confirmed in DNA from cultures derived from abortus material. The detection of a completely methylated amplified sequence correlates with the detection of a fragile X chromosome in cytogenetic analysis, thus demonstrating the feasibility of direct DNA analysis of cultured amniocytes. Additional comparisons with cytogenetic and DNA linkage studies will determine the sensitivity of this new approach. We thank the cytogenetic technological staff at the Institute for Basic Research for their help in this study. Partial support for these studies was provided by the New York State Office of Mental Retardation and Developmental Disabilities and by grant MCJ36058702 from the Bureau of Maternal and Child Health.

Department of Genetics, New York State Institute for Basic Research

Developmental Disabilities, Staten Island, NY 10314, USA in

CARL S. DOBKIN XIAO-HUA DING EDMUND C. JENKINS MICHAEL S. KRAWCZUN

Department of Pediatrics, Division of Human Genetics, North Shore University Hospital —Cornell Medical College, Manhasset, NY

W. TED BROWN PONMANI GOONEWARDENA

Department of Pediatrics, Division of Medical Genetics, Mount Sinai Hospital Medical Center, New York

JUDY WILLNER

CNRS Laboratory for Molecular Genetics of Eucaryotes and INSERM Unit 184, Faculty of Medicine, Strasbourg, France

DOMINIQUE HEITZ

with counts above 50 x 109 were PCR positive. By examining cases for which at least 50 x 101 frozen cells were available, Maurer et al may have unwittingly selected a higher proportion of cases carrying the Bcr-Abl rearrangement. This work has been supported in part by AIRC.

Department of Biomedical Science and Human Oncology, University of Turin, 10126 Turin, Italy

Institute of Haematology. "La Sapienza" University, Rome

1. Maurer

Jenkins EC, Brown WT, Duncan CJ, et al. Feasibility of fragile X chromosome prenatal diagnosis demonstrated. Lancet 1981; ii: 1292. 2. Jenkins EC, Krawczun MS, Brooks SE, et al. Laboratory aspects of prenatal fra(X) detection, In: Willey AM, Murphy PD, eds. Fragile X/cancer cytogenetics. New York: Wiley-Liss, 1991: 27-42. 3. Brown WT, Jenkins EC, Gross A, et al. Clinical use of DNA markers in the fragile (X) syndrome for carrier detection and prenatal diagnosis, In: Willey AM, Murphy PA, eds. Nucleic acid probes in diagnosis of human genetic diseases. New York: Alan R Liss, 1988: 11-34. 4. Oberle I, Rousseau F, Heitz D, et al. Instability of a 550 base pair DNA segment and abnormal methylation in fragile X syndrome. Science 1991; 252: 1097-102. 5. Verkerk AJMH, Pieretti M, Sutcliffe JS, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991; 65: 905-14. 6. Yu S, Pritchard M, Kremer E, et al. Fragile X genotype characterized by an unstable region of DNA. Science 1991, 252: 1179-81. 1.

Detection of

Ph1-positive acute lymphoblastic leukaemia by PCR SIR,-Maurer et all have published a retrospective study on a large series of patients with acute lymphoblastic leukaemia (ALL). They used the polymerase chain reaction (PCR) to detect Bcr-Abl hybrid transcripts associated with the Philadelphia (Ph1) chromosome. 43% of the adult ALL patients and 50% of those with B-cell derived leukaemias were positive by PCR. This report implies that the percentage of ALL patients who carry a Bcr-Abl rearrangement may be higher than the proportion established by cytogenetic studies.2 Using a PCR procedure3 very similar to Maurer’s we have started to analyse prospectively ALL cases included in a multicentre Italian study (GIMEMA LAL 0288). So far we have examined 49 consecutive cases (15 children and 34 adults; 8 with T-cell and 41 with B-cell leukaemias). Bcr-Abl transcripts were detected in 10 patients (20%), all in the B-cell group (26%); 5 cases displayed the p210 type junction and 5 the pi 90 type. Among the adults PCR positivity was 26% (9/34) (9/29 for B-cell cases). Although the series is smaller than that suggested by Maurer et al, our prospective study does suggest that the incidence of ALL carrying a Bcr-Abl rearrangement, as established by PCR, may be lower than that retrospectively determined by Maurer et al and more similar to that predicted by cytogenetic studiesThe discrepancy may be due not only to epidemiological or environmental factors but also, in part, as Maurer et al state, to the fact that the white cell count seems to be higher in PCR-positive cases. In our series 6 out of 13 cases (46%)

FRANCESCO LO COCO MARINA FRONTANI LUCIANA ANNINO FRANCO MANDELLI, for the GIMEMA

Cooperative Study Group

J, Janssen WGJ, Thiel E, et al Detection of chimeric BCR-ABL genes in lymphoblastic leukemia by the polymerase chain reaction. Lancet 1991; 337:

acute

1055-58. 2. Bloomfield CD, Goldman AI, Alimena G, et al. Chromosomal abnormalities identify high risk and low risk patients with acute lymphoblastic leukemia. Blood 1986; 67: 415-20. 3. Lo Coco F, Mandelli F, Diveno D, et al. Therapy induced Ph’ suppression in chronic myeloid leukemia: molecular and cytogenetic studies in patients treated with alpha 2B IFN, high dose chemotherapy and autologous stem cells infusions. Bone Marrow Transpl 1990; 6: 253-58.

CINDY BENSON

FRANCOIS ROUSSEAU

GIUSEPPE SAGLIO ANGELO GUERRASIO CLAUDIA ROSSO

Setting the record straight on low-dose heparin SIR,-In Dr Shulman’s view (Sept 7, p 619) it is incorrect to believe that perioperative low-dose regimens of heparin prevent deep vein thrombosis by an anticoagulant effect. He does not consider the evidence that there is a correlation between efficacy of low-dose heparin regimens and their anticoagulant effect. Both our departmentl,2 and the Lausanne group3 have shown that the effectiveness of low-dose heparin in hip surgery is improved if the dose is adjusted on the basis of the activated partial thromboplastin time (APTT). Both the adjusted dose schemes2,3 used in these studies aimed to give just sufficient heparin to ensure that blood heparin concentrations were detectable with sensitive APTT methods, and indicated the worth of heparin monitoring by APTT. Undue bleeding was not observed. These findings, however, do not negate Shulman’s view that the protective effect of low-dose heparin is attributable to its binding on endothelium, reinforcing the normal antithrombotic action of endogenous heparin activity on the endothelial surfaces. The detection of circulating heparin by APTT may indicate that sufficient heparin has been given to saturate all the heparin-binding sites on the endothelium, thus achieving its maximum antithrombotic potential. UK Reference Laboratory for Anticoagulant Reagents and Control,

Withington Hospital, Manchester M20 8LR, UK

L. POLLER D. A. TABERNER

1. Poller L, Tabemer DA, Sandilands DG, et al. An evaluation of APTT monitoring of low dose heparin m hip surgery. Thromb Haemost 1982; 47: 50-53. 2. Taberner DA, Poller L, Thomson JM, et al. Randomized study of adjusted versus fixed low dose heparin prophylaxis of deep vein thrombosis in hip surgery. BrJ Surg 1989; 76: 933-35. 3. Levraz PF, Richard J, Bachmann F, et al. Adjusted versus fixed dose subcutaneous heparin in the prevention of deep vein thrombosis after total hip replacement. N Engl J Med 1983; 309: 954-58.

CORRECTIONS Heparln treatment in sinus venous thrombosis.-In this article (Sept 7, 597), the additional 39 patients in Period III(Patients and methods) were seen from March, 1984, to May, 1991, and not May, 1985. p

Cryoglobulinaemia and serological markers of hepatitis viruses.-In the table of this letter (Sept 21, p 758) the first heading in the first column should have been Cryoglobulins instead of EMC.

Setting the record straight on low-dose heparin.

958 amplified and completely methylated; and the AF sample from the female fetus also carried a fragile X chromosome that was amplified and completel...
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