Molecular detection of t(8;21)/AML1-ETO in AML M1/M2: correlation with cytogenetics,morphology and immunophenotype

The t(8;21) identifies a subgroup of acute myeloid leukaemia (AML) with a relatively good prognosis which may merit different treatment. It is associated predominantly, but not exclusively, with AML M2, and corresponds to rearrangements involving the AML1 and ETO genes. AML1-ETO positive, t(8;21) negative cases are well recognized but their incidence is unknown. In order to determine optimal prospective AML1-ETO RT-PCR screening strategies, we analysed 64 unselected AML M1 and M2 cases and correlated the results with other biological parameters. Molecular screening increased the overall detection rate from 8% to 14%. AML1-ETO was found in 3% (1/32) of AML M1 and 25% (8/32) of M2, including three patients without a classic t(8;21) but with chromosome 8 abnormalities. It was more common in younger patients. Correlation with morphology enabled development of a scoring system which detected all nine AML1-ETO-positive cases with a false positive rate of 7% (4/55). Although certain AML1-ETO-positive cases demonstrated characteristic immunological features (CD19 and CD34 expression, CD33 negativity), each of these markers was insufficiently specific to permit prediction in an individual case. We conclude that initial routine prospective molecular screening for AML1-ETO in all AMLs, combined with standardized morphological and immunological analysis, is desirable in order to produce improved prognostic stratification and to determine whether screening can ultimately be restricted to appropriate subgroups.     

LATE ONSET HUNTINGTON'S DISEASE AS A CAUSE OF DEMENTIA: WHERE SHOULD THE CLINICIAN'S INDEX OF SUSPICION LIE?

Our experience with two genetically confirmed cases of late onset Huntington's disease (HD) in a longitudinal dementia research study suggested that clinical misdiagnosis can easily occur. We therefore undertook genetic testing for HD in a further 84 elderly subjects, 81 of whom had come to postmortem; 75 subjects had dementia and nine were normal controls. A quarter of the demented group had demonstrated extrapyramidal symptoms in life but in none had HD formed part of the differential diagnosis. Although no genetically confirmed cases were found in this second group, the original cases serve as a reminder that late onset HD is a cause of dementia. Genetic confirmation should be sought when the condition forms part of the final differential diagnosis. Further studies conducted in the routine clinical setting are now required since it is in this environment that late onset HD is likely to be misdiagnosed in favour of other forms of dementia.     

Use of the Wearable External Cardiac Defibrillator in Children

Background: The wearable cardiac defibrillator (WCD) is an alternative to the implantation of cardioverter defibrillator (ICD) for patients at risk for sudden death who do not fulfill standard criteria for ICD implantation or in whom the risk:benefit ratio is equivocal. Published data pertaining to the WCD in children is sparse. We describe the utility of the WCD in children at a single tertiary care center. Methods: We retrospectively identified all patients aged birth to 18 years of age who were prescribed a WCD between January 1, 2007, and June 30, 2009. Patient information regarding diagnosis, clinical history, electrocardiograms, rhythm reports, and outcome at last follow‐up was reviewed. Information regarding the WCD was obtained including indication for use, patient compliance, and accuracy of rhythm determination, inappropriate and appropriate shock events, and other complications. Results: Since 2007, four patients age less than or equal to 18 years have been prescribed the WCD at our institution. None of the patients had an inappropriate shock. Two patients had documented noncompliance with wear, which resulted in failure to detect and treat a life‐threatening arrhythmia in one. Two patients required downsizing of the WCD during use in order to improve electrode contact and rhythm detection. Conclusions: The WCD is an option for children of appropriate size who are at increased risk for sudden cardiac death, but in whom the risk of ICD implantation outweighs the benefit. Careful patient selection and education is important to ensure safety, as noncompliance with wear was common in this series of children. (PACE 2010; 33:742–746)     

The impact of a rubella prevention policy on the outcome of rubella in pregnancy

Summary. Surveillance of rubella vaccination in schoolgirls has continued intensively in Edinburgh since 1970. Screening for rubella antibody of all women attending antenatal clinics has been available since 1974. The analysis of cases of rubella occurring in pregnancy during an outbreak in 1979 confirmed the efficacy of schoolgirl vaccination in the city but indicated poor implementation of postnatal vaccination. Eighteen (67%) of 27 proven cases occurred in women who were screened in previous pregnancies and not immunized. Of the total of 13 liveborn infants the only two with congenital rubella defects were born to mothers in this group. Rubella immunization of schoolgirls and women of childbearing age must receive continued intensive effort if the problems of rubella in pregnancy are to be eradicated.     

Follicle growth patterns and endocrinological abnormalities in infertile women with minor degrees of endometriosis

Summary. Eighteen patients whose only demonstrable cause of infertility was a minor degree of endometriosis and whose partners were normal, were investigated prospectively for one menstrual cycle using ultrasonography and endocrine profiles. Twelve cycles appeared to be normal. A luteinized unruptured follicle (LUF) occurred in two cycles and one patient had a follicular cyst. In a further two patients there was inadequate or abnormal folliculogenesis whilst in the last patient the follicle ruptured prematurely. This study describes the variety of endocrinological abnormalities found in women with mild endometriosis, and concludes that, in this series at least, there is a low frequency of LUF.     

Successful in vitro fertilization and pregnancy in a patient with autoimmune chronic active hepatitis and cirrhosis

Abstract Fertility is reduced in women with chronic active autoimmune hepatitis (AIH) and pregnancy is hazardous. This report describes a 33 year old woman with AIH and cirrhosis in whom a successful pregnancy was achieved following in vitro fertilization/embryo transfer. Disease exacerbation during pregnancy was controlled by azathioprine and an increased dose of prednisone, and a healthy child was delivered by Caesarean section at 36 weeks gestation. Since the perinatal care of preterm infants and the obstetric care available to women with complicated medical problems has improved markedly in recent years and since active disease can be controlled by adequate immunosuppressive therapy, we propose that it is justified to allow these patients access to in vitro fertilization programmes.     

The consistency of family and peer influences on the development of substance use in adolescence

Latent growth modeling (LGM) was used to analyse longitudinal data for adolescent substance use from five overlapping age cohorts (11, 12, 13, 14 and 15 years at first assessment) measured at four annual time points. An associative cohort-sequential model was tested for alcohol, cigarette and marijuana use with a sample of 345 adolescents (11–18 years old) from an urban area in the Pacific Northwestern region of the United Stales. Hypotheses concerning the shape of the growth curve, the extent of individual differences in the common trajectory over time, and the influence of family cohesion, peer encouragement and gender on initial substance use and shape of the growth curve were tested. Results indicated similarities between alcohol, cigarette and marijuana initial use and development, with peer encouragement and family cohesion predictive of initial levels of use, and changes in peer encouragement influencing the developmental trajectories of the three substances. Females were higher than males in initial status and developed less rapidly in their use of the substances than did males. Findings are discussed in terms of the similarities and differences in the developmental trajectories of the three substances and the importance of family and peer influences on these trends.     

The Involvement of General Practitioners in the Care of Patients with Human Immunodeficiency Virus Infection: Current practice and Future Implications

The objective was to determine the current use of their generalpractitioner (GP) by patients with human immunodeficiency virus(HIV) infection and whether such patients would be interestedin having ‘shared care’ between a specialist HIVclinic and their GP. A questionnaire was administered to 203HIV-positive men attending the HIV outpatient clinic of a centralLondon teaching hospital. The main outcome measures were patientcharacteristics, numbers of patients registered with a GP, numbersof patients with a GP aware of their diagnosis, contacts withthe GP in the last year and level of interest and shared care.Eighty-five per cent of patients were registered with a GP ofwhom 67% knew of the diagnosis. Those diagnosed for more than2 years were significantly more likely to have an informed GP.A total of 73% of those registered had visited their GP in theprevious year although only 27% had visited for an HIV-relatedproblem. Only 19% had a GP actively involved in their HIV care.In all 51% of the patients indicated an interest in having sharedcare between the clinic and their GP. A high proportion of HIVpatients are registered with and attend a GP although they rarelyconsult for HIV-related problems. A significant proportion ofpatients expressed interest in having shared care suggestingthat there is the potential for increased GP involvement inthe care of patients with HIV infection.