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Research News for August 1996

Apo B good predictor of IHD
Reporting in Circulation, 1996;94:273-278, Dr. Jean-Pierre Despres and colleagues at Laval University in Ste-Foy, Quebec, indicated Apo B may be a better marker for ischemic heart disease than a lipid profile. He and a multicenter team studied a cohort of more than 2,100 men aged 35 to 64 years to assess plasma lipid, apo B and apo A-1 levels as well as other risk factors for IHD at baseline. During a five-year follow-up period, they found a 20% elevation in apo B levels was associated with a 34% increased risk of developing IHD. Comparing the predictive association between total/HDL cholesterol and IHD, Dr. Despres reported that "...results of the present prospective study suggest that apo B is a better predictor of IHD" and that "...the use of [total/HDL] ratio, as opposed to apo B, may not adequately reflect the effects of lipid-lowering therapy, because the lack of change in the ratio may be the result of parallel changes in both of its components."

Bone marrow transplant : cure for sickle cell anemia
Bone marrow transplantation can provide a cure for sickle cell disease. Dr. Keith M. Sullivan of the Fred Hutchinson Cancer Research Center in Seattle reported in the New England Journal of Medicine 1996;335:369-376,426-428, that he and investigators in North America, Brazil and Europe performed allogeneic stem-cell transplantation in 22 children less than 16 years of age who had symptomatic sickle cell disease and HLA-identical siblings. After follow-up of 2 years, 20 of the 22 patients survived and sustained engraftment with 85 percent or more donor cells was demonstrated...in 16 of the 20 surviving patients. Sickle cell disease recurred in three patients, and graft failure occurred in a fourth. Transfusions have been discontinued in the 16 patients with engraftment, and all have remained free of disabling symptoms. The optimal timing of bone marrow transplantation in the course of sickle cell anemia still remains uncertain Dr. Sullivan comments. "The study included patients who appeared to have a high risk of severe morbidity and early death...Marrow transplantation might therefore be better if performed early in the course of sickle cell disease."

Heart disease linked to chromosome 22
A study published in the Journal of Pediatrics links a deletion on chromosome 22 to the ventricular outflow tracts and aortic arch defects and other common causes of congenital heart disease. Researchers at the Wessex Cardiothoracic Centre of Southampton General Hospital, led by Dr. Steven A. Webber, assessed the incidence of microdeletions of chromosomal region 22q11 in a sample of infants with abnormalities of the ventricular outflow tracts, aortic arch and other manifestations of velocardiofacial syndrome.

Protein C linked to stroke
Resistance to activated protein C, a protein that is the result of a mutation in the gene for coagulant factor V, has been linked to an increased risk of venous thromboembolism. Now, a study in the August issue of the Annals of Internal Medicine, Dutch researchers report that activated protein C resistance is also linked to an increased risk of cerebrovascular disease characterized by stroke and transient ischemic attack. Researchers at Erasmus University in Rotterdam measured response to activated protein C in 115 patients with a history of myocardial infarction, 112 patients with a history of stroke and in 222 age-matched healthy controls. None of the patients was on anticoagulation therapy. They found no association between resistance to activated protein C and risk of MI, but they did find that the risk for stroke increased inversely with a resistance to activated protein C.

PCR used to diagnose CNS diseases
A report in AIDS (1996;10:951-958) indicated polymerase chain reaction of cerebrospinal fluid to be a sensitive and effective tool for detection of opportunistic diseases of the CNS in HIV-infected patients. Researchers used PCR to detect HSV types 1 and 2, varicella zoster virus, CMV, Epstein-Barr virus, human herpesvirus 6 and JC virus DNA in the cerebrospinal fluid of 500 HIV-infected patients. The report concludes that "...cerebrospinal fluid PCR should become a major tool for the diagnosis and monitoring of viral diseases of the CNS in HIV-infected patients.

PCR used for RhD testing
Polymerase chain reaction-based analysis of uncultured amniocytes is highly accurate in the assessment of the RhD status of the fetus. Researchers at the University of Utah used a monoclonal-polyclonal antiserum preparation from Ortho Diagnostic Systems, and performed PCR analysis on 347 amniotic fluid samples. The test results of RhD antigen status agreed with that of the fetal serologic RhD blood types in all but one sample.

Genetic root of MS found
An international research team has identified DNA regions that may house genes that can cause individuals to become susceptible to multiple sclerosis (MS). The scientists report in the August issue of Nature Genetics the identification of 19 candidate regions resulting from a search spanning all the DNA contained in the human genome. No gene within any of these regions is likely to act alone to cause MS, the researchers conclude, but some of these regions are likely to contain genes that may act in concert with other genes and environmental factors to bring about MS. The study included blood from 643 individuals, persons with MS as well as unaffected relatives. The authors suggest "there is no one gene responsible for causing multiple sclerosis. We believe it is the interaction of several genes, potentially triggered by an environmental stimulus, that causes the immune system to attack the myelin fibers. The genes may work independently or together, and the particular combination of genes that are inherited may affect when symptoms develop or how the disease progresses. There is a lot of work to be done."

Slide storage jeopardizes results
A study in the Journal of the National Cancer Institute (1996;88:1054-1059) reported the test results for cut sections from formalin-fixed, paraffin-embedded breast carcinomas and prepared slides that were stored for periods of 2, 4, 8 or 12 weeks at room temperature. The slides were stained and evaluated for the effects of storage among sections cut from the same block. They found the intensity of p53 staining decreased over time in 9 of the 12 cases studied. In addition, three of the cases that were initially scored p53-positive were scored p53-negative at 12 weeks. They also noted a significant loss of immunoreactivity for factor VIII-related antigen, estrogen receptor and Bcl-2 protein at 12 weeks.

Free PSA judged not as useful as PSMA
A report in Cancer (1996;78:809-818) has concluded that free PSA does not provide additional diagnostic or prognostic benefit compared with conventional total prostate-specific antigen screening; and that prostate specific membrane antigen does provide significant additional prognostic information. The researchers studied a group of 266 individuals undergoing advanced screening for prostate cancer and found that prostate-specific membrane antigen showed the best correlation with stage of the primary tumor in the screened group...In patients with metastatic carcinoma, elevated [prostate-specific membrane antigen] correlated best with a poor prognosis."

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