Prenatal diagnosis of tetrasomy 18p using multiplex fluorescent PCR and comparison with a variety of techniques

We report genetic characterization of isochromosome 18p using a combination of cytogenetic and molecular genetic methods, including multiplex fluorescent PCR. The patient was referred for chorionic villus sampling (CVS) due to advanced maternal age and maternal anxiety. The placental karyotype was 47,XX,+mar, with the marker having the appearance of a small supernumerary isochromosome. Because differentiating between isochromosomes and other structural rearrangements is normally very difficult, a variety of genetic tests including fluorescence in situ hybridization (FISH), PCR, and multiplex fluorescent PCR were undertaken to determine chromosomal origin and copy number and, thus, allow accurate diagnosis of the corresponding syndrome. FISH determined that the marker chromosome contained chromosome 18 material. PCR of a variety of short tandem repeats (STRs) confirmed that there was at least one extra copy of the maternal 18p material. However, neither FISH nor PCR could accurately determine copy number. Multiplex fluorescent PCR (MF-PCR) of STRs simultaneously determined that: (1) the marker included 18p material; (2) the marker was maternal in origin; (3) allele copy number indicated tetrasomy; and (4) contamination of the sample could be ruled out. Results were also rapid with accurate diagnosis of the syndrome tetrasomy 18p possible within 5 hours.

Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents

Primary aldosteronism (PA) is a common form of endocrine hypertension previously believed to account for less than 1% of hypertensive patients. Hypokalemia was considered a prerequisite for pursuing diagnostic tests for PA. Recent studies applying the plasma aldosterone/plasma renin activity ratio (ARR) as a screening test have reported a higher prevalence. This study is a retrospective evaluation of the diagnosis of PA from clinical centers in five continents before and after the widespread use of the ARR as a screening test. The application of this strategy to a greater number of hypertensives led to a 5- to 15-fold increase in the identification of patients affected by PA. Only a small proportion of patients ( between 9 and 37%) were hypokalemic. The annual detection rate of aldosterone-producing adenoma (APA) increased in all centers ( by 1.3-6.3 times) after the wide application of ARR. Aldosterone-producing adenomas constituted a much higher proportion of patients with PA in the four centers that employed adrenal venous sampling ( 28 - 50%) than in the center that did not (9%). In conclusion, the wide use of the ARR as a screening test in hypertensive patients led to a marked increase in the detection rate of PA. Copyright © 2004 by The Endocrine Society

Symptoms and diagnosis of borderline, early and advanced epithelial ovarian cancer

Objective. To document symptoms associated with borderline, early and advanced ovarian cancer and identify personal characteristics associated with early versus late diagnosis. Methods. Information concerning symptoms and diagnosis history was available from 811 women with ovarian cancer who took part in an Australian case–control study in the early 1990s. Women were classified into three groups for comparison based on their diagnosis: borderline, early (stage I–II) and advanced (stage III–IV) invasive cancer. Results. Sixteen percent of women with borderline tumors, 7% with early cancer and 4% with advanced cancer experienced no symptoms before diagnosis (P < 0.0001). Among women with symptoms, abdominal pain (44%) or swelling (39%) were most frequently reported; an abdominal mass (12%) and gynecological symptoms (12%) were less common. Compared to advanced stage cancer, women with early stage cancer were more likely to report an abdominal mass or urinary symptoms but less likely to report gastrointestinal problems or general malaise. General malaise and ‘other’ symptoms were least common in borderline disease. Older women, and those with higher parity or a family history of breast or ovarian cancer, were more likely to be diagnosed at an advanced stage of disease. Conclusions. Women who experience persistent or recurrent abdominal symptoms, particularly swelling and/or pain should be encouraged to seek medical attention and physicians should be alert to the possibility of ovarian cancer even in the absence of an abdominal mass. Further information about the prevalence of these symptoms in the general population is essential to assist physicians in patient management.

Influence of socioeconomic deprivation on the primary care burden and treatment of patients with a diagnosis of heart failure in general practice in Scotland: population based study

Objectives To examine whether there are socioeconomic gradients in die incidence, prevalence, treatment, and follow up of patients with heart failure in primary care. Design Population based study. Setting 53 general practices (307741 patients) participating in the Scottish continuous morbidity recording project between 1 April 1999 and 31 March 2000. Participants 2186 adults with heart failure. Main outcome measures Comorbid diagnoses, frequency of visits to general practitioner, and prescribed drugs. Results 2186 patients with heart failure were seen (prevalence 7.1 per 1000 population, incidence 2.0 per 1000 population). The age and sex standardised incidence of heart failure increased with greater socioeconomic deprivation, from 1.8 per 1000 population in the most affluent stratum to 2.6 per 1000 population in the most deprived stratum (odds ratio 1.44, P=0.0003). On average, patients were seen 2.4 times yearly, but follow up rates were less frequent with increasing socioeconomic deprivation (from 2.6 yearly in the most affluent subgroup to 2.0 yearly in the most deprived subgroup, P=0.00009). Overall, 812 (80.6%) patients were prescribed diuretics, 396 (39.3%) angiotensin converting enzyme inhibitors, 216 (21.4%) beta blockers, 208 (20.7%) digoxin, and 86 (8.5%) spironolactone. The wide discrepancies in prescribing between different general practices disappeared after adjustment for patient age and sex. Prescribing patterns did not vary by deprivation categories on univariate or multivariate analyses. Conclusions Compared with affluent patients, socioeconomically deprived patients were 44% more likely to develop heart failure but 23% less likely to see their general practitioner on an ongoing basis. Prescribed treatment did not differ across socioeconomic gradients.

Frequency of insomnia report in patients with obstructive sleep apnoea hypopnea syndrome (OSAHS)

Background and purpose: Insomnia and Obstructive Sleep Apnoea Hypopnea Syndrome (OSAHS) are the two most common sleep disorders, and both have significant associated health costs. Despite this, relatively little is known about the prevalence or impact of insomnia in those with OSAHS, although a recent study suggested there may be substantial comorbidity between these disorders [Chest 120 (2001) 1923-9]. The primary aim of this study was to further explore the prevalence of insomnia in OSAHS. A secondary aim was to assess the effect of factors that may impact on both conditions, including mood and sleep-beliefs. Patients and methods: Consecutive patients referred to an accredited Sleep Investigations Unit (n = 105) completed a brief standardized battery of validated questionnaires assessing sleep-related variables and mood. Results: Results showed a high rate of prevalence of clinical insomnia in this OSAHS population, and a strong positive correlation between OSAHS and insomnia symptom severity. Further, OSAHS patients with comorbid insomnia had increased levels of depression, anxiety and stress compared to patients with OSAHS-only, and both patient groups reported similar and significant levels of dysfunctional beliefs about sleep. Findings in relation to habitual sleep, assessed using subjective (diary) and objective criteria (polysomnogram), were mixed but generally showed greater sleep disturbance among those with OSAHS-insomnia compared to those with OSAHS-only. Conclusions: Overall these findings suggest that comorbidity of insomnia in OSAHS patients may lead to increased OSAHS severity and that patients with both conditions may experience more symptoms relating to depression, anxiety and stress. These findings underscore the need for insomnia assessment and management services, even in clinics that primarily service patients with OSAHS. (C) 2004 Elsevier B.V. All rights reserved.

Use of multiple biomarkers for a molecular diagnosis of prostate cancer

The identification of biomarkers capable of providing a reliable molecular diagnostic test for prostate cancer (PCa) is highly desirabie clinically. We describe here 4 biomarkers, UDP-N-Acetyl-alpha-D-galactosamine transferase (GalNAc-T3; not previously associated with PCa), PSMA, Hepsin and DD3/PCA3, which, in combination, distinguish prostate cancer from benign prostate hyperplasia (BPH). GalNAc-T3 was identified as overexpressed in PCa tissues by microarray analysis, confirmed by quantitative real-time PCR and shown immunohistochemically to be localised to prostate epithelial cells with higher expression in malignant cells. Real-time quantitative PCR analysis across 21 PCa and 34 BPH tissues showed 4.6-fold overexpression of GalNAc-T3 (p = 0.005). The noncoding mRNA (DD3/PCA3) was overexpressed 140-fold (p = 0.007) in the cancer samples compared to BPH tissues. Hepsin was overexpressed 21-fold (p = 0.049, whereas the overexpression for PSMA was 66-fold (p = 0.047). When the gene expression data for these 4 biomarkers was combined in a logistic regression model, a predictive index was obtained that distinguished 100% of the PCa samples from all of the BPH samples. Therefore, combining these genes in a real-time PCR assay represents a powerful new approach to diagnosing PCa by molecular profiling. (c) 2005 Wiley-Liss, Inc.

Comparison of specificity of quantitative myocardial contrast echocardiography for diagnosis of coronary artery disease in patients with versus without diabetes mellitus

Impaired coronary flow reserve is widely reported in diabetes mellitus (DM) but its effect on myocardial contrast echocardiography (MCE) is unclear. We sought to identify whether DM influences the accuracy of qualitative and quantitative assessment of coronary artery disease (CAD) using MCE in 83 patients who underwent coronary angiography (60 men, 27 with DM; 56 +/- 11 years;). Destruction replenishment imaging was performed at rest and after combined dipyridamole-exercise stress testing. Ischemia was identified by the development of new wall motion abnormalities, qualitative MCE (new perfusion defects apparent 1 second after flash during hyperemia), and quantitative MCE (myocardial blood flow reserve < 2.0 in the anterior circulation). Qualitative and quantitative assessment of perfusion was feasible in 100% and 92% of patients, respectively. Significant left anterior descending coronary stenosis (> 50% by quantitative angiography) was present in 28 patients (including 8 with DM); 55 patients had no CAD (including 19 with DM). The myocardial blood flow reserve was reduced in patients with coronary stenosis compared with those with no CAD (1.6 +/- 1.1 vs 3.8 +/- 2.5, p < 0.001). Among patients with no CAD, those with DM had an impaired flow reserve compared with control patients without DM (2.4 +/- 1.0 vs 4.5 +/- 2.8, p = 0.003). In conclusion, DM significantly influenced the quantitative, but not the qualitative, assessment of MCE, with a marked reduction in specificity in patients with DM. (c) 2005 Elsevier Inc. All rights reserved.

The experience of insomnia among older women

Study Objectives: To measure sleeping difficulty and sleep quality among older women, explore experience and attitudes towards sleep, and test for negative association between difficulty sleeping and health-related quality of life. Design: Four-year longitudinal study. Setting: Women were participants in the Australian Longitudinal Study on Women's Health. Participants: Women were sampled according to use of sleeping medication and classified into 4 groups: sleeping badly and using sleeping medications; not sleeping badly, but using sleeping medications; sleeping badly, not using sleeping medications; not sleeping badly, not using sleeping medications. Interventions: None. Measurements and Results: Sleeping difficulty and sleeping-medication use were measured at Survey 1, Survey 2 (3 years later), and Survey 3 (4 years later). Survey 3 included: Nottingham Health Profile Sleep Subscale, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Geriatric Depression Scale, Duke Social Support Index, Medical Outcomes Study Short-Form 36-item Health Survey, and a 21-item life events scale. Survey 3 was returned by 1011 women (84%). Sleeping problems were negatively associated with SF-36 subscale scores. Most associations remained significant after comorbid conditions, Geriatric Depression Scale, life events scores, and medication use were added to models. Most women with sleeping problems (72%) sought help from a doctor, and 54% used prescribed sleeping medications in the past month. Conclusions: Sleeping difficulty is a serious symptom for older women and is associated with poorer quality of life. Some of this effect can be explained by comorbidities, depression scores, life events, and use of sleeping medications.

Comparative assessment of the gelatin particle agglutination test and an enzyme-linked immunosorbent assay for diagnosis of strongyloidiasis

The performances of the gelatin particle agglutination test (GPAT) and enzyme-linked immunosorbent assay (ELISA) for the diagnosis of strongyloidiasis with reference to the results of the agar plate culture technique (APCT) were evaluated with samples from 459 individuals from communities in northeast Thailand where strongyloidiasis is endemic. The prevalence of strongyloidiasis in five sample groups determined by GPAT varied between 29.3 and 61.5% (mean, 38.8%). ELISA and APCT, employed concurrently, gave lower prevalence rates of 27.5% (range, 21.6 to 42.1%) and 22.7% (range, 12.7 to 53.8%), respectively. By using APCT as the standard method, the sensitivity of GPAT was generally higher than that of ELISA (81 versus 73%). The specificity of GPAT was slightly lower than that of ELISA (74 versus 86%). The resulting GPAT titers exhibited positive linear relationships with the ELISA values (optical density at 490 nm) (P < 0.05), which suggests that the GPAT titer also reflects the levels of specific antibody comparable to those reflected by the ELISA values. Based on the relative ease and simplicity of use of the technique as well as the acceptable rates of sensitivity and specificity of the test, GPAT is more practical for screening for strongyloidiasis than the conventional ELISA.

Diagnosis of autistic spectrum disorders in Queensland: Variations in practice

Objective: For both paediatricians and child psychiatrists, referrals to assess possible autistic spectrum disorders (ASD) are increasing. This study examines current practices of medical specialists in the assessment of these disorders. Methods: An anonymous, self-report questionnaire was sent to all Queensland paediatricians and child psychiatrists. The survey elicited frequencies of consultation for ASD, diagnostic method, advice provided and perceived adequacy of training for this work. Results: Responses were received from 79 (85%) eligible paediatricians and 26 (58%) eligible child psychiatrists. For one-third of all clinicians, new consultations for possible ASD occurred as often as 2-3 times per week. Most specialists approached the clinical diagnosis of ASD by considering history from different sources and professional assessments. Paediatricians (86%) were more likely than child psychiatrists (62%) to request genetic studies for children with severe autism (P = 0.01). Both general paediatricians and developmental paediatricians perceived level of training for possible ASD consultations was significantly worse than child psychiatrists (P < 0.001 and P = 0.02, respectively), but no difference was found between paediatric groups (P = 0.27). Perceived adequacy of specialist training was not associated with length of experience in clinical practice. Conclusion: Medical practice in Queensland around diagnosis of ASD is characterized by considerable variability. There is still a long way to go if we are to achieve consistency around medical issues of organic diagnosis and practices impacting on health as well as consideration of differential developmental diagnoses. The finding that recently trained paediatricians felt just as unprepared for this work as their older colleagues suggests that the graduate training response to this 'new morbidity' has not been adequate.

Psychosocial and non-psychosocial risk factors for the new diagnosis of diabetes in elderly women

Objectives: Determine psychosocial variables associated with the new diagnosis of diabetes in elderly women. Examine whether variables remained significant predictors after controlling for non-psychosocial risk factors and the frequency of doctor visits. Research design and methods: A longitudinal cohort study was conducted using data from 10 300 women who completed a survey in 1996 and 1999. The women were aged between 70 and 74 years of age in 1996. The were asked to provide self-reports on a number of psychosocial and non-psychosocial variables in 1996 and on whether they had been diagnosed for the first time with diabetes in the 3-year period. The relationships between the potential risk factors and new diagnosis of diabetes were examined using binary logistic regression analysis. Results: Univariate results showed that not having a current partner, having low social support and having a mental health index score in the clinical range were all associated with higher risks of being diagnosed with diabetes for the first time. However the multivariate results showed that only a mental health index score in the clinical range and not having a current partner provided unique prediction of being newly diagnosed with diabetes. Of the non-psychosocial variables measured, only having a high BMI and hypertension were associated with increased risks of new diagnosis, while there was also evidence of a U shaped relationship between alcohol consumption and new diagnosis. Even after adjusting for frequency of doctor visits and non-psychosocial risk factors, a mental health index in the clinical range proved to still be a significant risk factor. Conclusions: A score on the mental health index that is within the clinical range is an independent risk factor for the new diagnosis of diabetes in elderly women. (c) 2006 Elsevier Ireland Ltd. All rights reserved.