Hilary Watt

Apolipoproteins and ischaemic heart disease: implications for screening

Apolipoproteins and lipids are established risk factors of ischaemic heart disease (IHD) but their efficacy as screening tests is not known. We therefore examined the mortality from IHD and serum concentrations of lipids and apolipoproteins in a prospective study of 21,520 men aged 35-64 years. Serum apo B was the apolipoprotein most strongly associated with IHD risk; a decrease in apo B of 10% was associated with 22% lower risk of IHD. However, measurement of apo B alone detected only 17% of all IHD deaths at the cost of a 5% false-positive rate. Combining apo B with apo AI and apo (a) increased the detection rate to 19%. With systolic blood pressure, smoking, and family history of IHD the detection rate increased to 28%. We conclude that screening for IHD by measuring apo B alone or with apo AI and apo (a) is too poor to discriminate between recommending drug therapy or lifestyle change for some and not others. It is not advisable to screen for IHD by measuring any combination of cholesterol, apo B, apo AI, apo (a) and the other risk factors. The primary aim in prevention of ischaemic heart disease should be to lower the risk factors in the population.

Fetal loss in Down syndrome pregnancies

It is recognized that pregnancies with Down syndrome are liable to end in spontaneous fetal loss. It is important to determine the magnitude of this effect so that it can be taken into account when assessing the results of antenatal screening programmes for Down syndrome. Failure to do so will tend to overestimate the detection rate in intervention studies in which the screening results are used to identify women for a diagnostic test and the offer of a termination of pregnancy if indicated.

Change in rates of cerebral atrophy over time in early-onset Alzheimer's disease: longitudinal MRI study

The extent to which cerebral atrophy in Alzheimers disease changes with time is unknown. We used multiple MRI scans to measure progression of cerebral atrophy in 12 patients with Alzheimers disease who were followed up from a presymptomatic stage through to moderately severe dementia. Analysis with hierarchical regression models with quadratic terms in time provided evidence of increasing yearly percentage losses in brain volume. At the time when patients were judged to have mild dementia (mini-mental state examination score MMSE=23), mean yearly loss of brain volume was 2.8% (95% CI 2.3-3.3), which rose by 0.32% per year (0.15-0.50). Our findings reinforce the need for early diagnosis and therapeutic intervention in Alzheimers disease.

Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study

Background: The seed powder of the leguminous plant, Mucuna pruriens has long been used in traditional Ayurvedic Indian medicine for diseases including parkinsonism. We have assessed the clinical effects and levodopa (l-dopa) pharmacokinetics following two different doses of mucuna preparation and compared them with standard l-dopa/carbidopa (LD/CD). Methods: Eight Parkinson’s disease patients with a short duration l-dopa response and on period dyskinesias completed a randomised, controlled, double blind crossover trial. Patients were challenged with single doses of 200/50 mg LD/CD, and 15 and 30 g of mucuna preparation in randomised order at weekly intervals. l-Dopa pharmacokinetics were determined, and Unified Parkinson’s Disease Rating Scale and tapping speed were obtained at baseline and repeatedly during the 4 h following drug ingestion. Dyskinesias were assessed using modified AIMS and Goetz scales. Results: Compared with standard LD/CD, the 30 g mucuna preparation led to a considerably faster onset of effect (34.6 v 68.5 min; p = 0.021), reflected in shorter latencies to peak l-dopa plasma concentrations. Mean on time was 21.9% (37 min) longer with 30 g mucuna than with LD/CD (p = 0.021); peak l-dopa plasma concentrations were 110% higher and the area under the plasma concentration v time curve (area under curve) was 165.3% larger (p = 0.012). No significant differences in dyskinesias or tolerability occurred. Conclusions: The rapid onset of action and longer on time without concomitant increase in dyskinesias on mucuna seed powder formulation suggest that this natural source of l-dopa might possess advantages over conventional l-dopa preparations in the long term management of PD. Assessment of long term efficacy and tolerability in a randomised, controlled study is warranted.

Endometrial Thickness as a Test for Endometrial Cancer in Women With Postmenopausal Vaginal Bleeding

OBJECTIVE To assess the value of endometrial thickness measurement as a test for endometrial cancer in post‐menopausal women with vaginal bleeding (symptomatic women). DATA SOURCES We conducted a literature search using the MEDLINE database from 1991 to 1997, and the key words “vaginal ultrasonography” and “endometrial thickness measurement.” The review was limited to original research reports written in English, concerning symptomatic women having vaginal ultrasonography before a diagnostic test and not receiving tamoxifen. STUDY SELECTION A total of 48 studies were identified. A questionnaire was sent to the corresponding author of each paper requesting supplementary information. Data were included in our analysis if the corresponding author was able to supply information on the median endometrial thickness in unaffected symptomatic women and the endometrial thickness values in affected women. Nine studies were thus included in our meta‐analysis, representing 3483 women without endometrial cancer and 330 women with endometrial cancer. TABULATION, INTEGRATION, AND RESULTS The median endometrial thickness in women with endometrial cancer was 3.7 times that in unaffected women at the same center, and with the same menopausal status and same hormone replacement therapy use category. The detection rate was 63% (95% confidence interval 58, 69) for a 10% false‐positive rate, or 96% (95% confidence interval 94, 98) for a 50% false‐positive rate. CONCLUSION Endometrial thickness measurement in symptomatic women does not reduce the need for invasive diagnostic testing because 4% of the endometrial cancers would still be missed with a false‐positive rate as high as 50%.

Predictors of falls and fractures in bradykinetic rigid syndromes: a retrospective study

Background: Falls and fractures contribute to morbidity and mortality in bradykinetic rigid syndromes. Methods: The authors performed a retrospective case notes review at the Queen Square Brain Bank for Neurological Disorders and systematically explored the relation between clinical features and falls and fractures in 782 pathologically diagnosed cases (474 with Parkinson’s disease (PD); 127 progressive supranuclear palsy (PSP); 91 multiple system atrophy (MSA); 46 dementia with Lewy bodies (DLB); 27 vascular parkinsonism; nine Alzheimer’s disease; eight corticobasal degeneration). Results: Falls were recorded in 606 (77.5%) and fractures in 134 (17.1%). In PD, female gender, symmetrical onset, postural instability, and autonomic instability all independently predicted time to first fall. In PD, PSP, and MSA latency to first fall was shortest in those with older age of onset of disease. Median latency from disease onset to first fall was shortest in Richardson’s syndrome (12 months), MSA (42), and PSP-parkinsonism (47), and longest in PD (108). In all patients fractures of the hip were more than twice as common as wrist and forearm fractures. Fractures of the skull, ribs, and vertebrae occurred more frequently in PSP than in other diseases. Conclusion: Measures to prevent the morbidity associated with falls and fractures in bradykinetic rigid syndromes may be best directed at patients with the risk factors identified in this study.

The normal appearing grey matter in primary progressive multiple sclerosis: a magnetisation transfer imaging study

Abstract.Background: In 10–15 % of patients with multiple sclerosis (MS), the clinical course is characterized by slow progression in disability without relapses (primary progressive (PP) MS). The mechanism of disability in this form of MS is poorly understood. Using magnetization transfer ratio (MTR) imaging, we investigated normal appearing white matter (NAWM) and normal appearing grey matter (NAGM) in PPMS and explored the relationship of MTR measures with disability. Methods: Thirty patients with PPMS and 30 age matched controls had spin echo based MTR imaging to study lesions and normal appearing tissues. The brain was segmented into NAWM and NAGM using SPM99 with lesions segmented using a semiautomated local thresholding technique. A 75 % probability threshold for classification of NAWM and NAGM was used to diminish partial volume effects. From normalized histograms of MTR intensity values, six MTR parameters were measured. Mean lesion MTR and T2 lesion volume were also measured. Disability was assessed using Kurtzkes expanded disability status scale (EDSS). Results: Compared with controls, patients exhibited a significant reduction in mean NAWM (p = 0.001) and NAGM (p = 0.004) MTR. Spearmans rank correlation of EDSS with the six MTR parameters in NAWM and NAGM, mean lesion MTR, and T2 lesion volume, was only significant with mean NAGM MTR (r = −0.41, p = 0.02), the 25th percentile of NAGM MTR intensity (r = −0.37, p = 0.05), and T2 lesion volume (r = 0.39, p = 0.04). Multiple regression analysis of the relationship between EDSS and 4 MR parameters representing each tissue type (mean NAWM MTR, mean NAGM MTR, mean lesion MTR, T2 lesion volume) showed that the association of EDSS with mean NAGM MTR remained significant. Conclusions: There appear to be significant abnormalities in the NAGM in PP MS. Further investigation of the pathological basis and functional significance of grey matter abnormality in PPMS is warranted.

Olfactory function distinguishes vascular parkinsonism from Parkinson’s disease

Objective: To compare olfactory function in vascular parkinsonism and Parkinson’s disease diagnosed according to published clinical diagnostic criteria. Methods: The University of Pennsylvania smell identification test (UPSIT) was carried out in 14 patients with vascular parkinsonism, 18 with Parkinson’s disease, and 27 normal controls matched for age, sex, and smoking status. Results: UPSIT scores in vascular parkinsonism (mean 26.1, 95% confidence interval, 23.1 to 29.0) were significantly better than in Parkinson’s disease (mean 17.1 (14.5 to 19.7)) (p<0.0001), and did not differ from the healthy controls (mean 27.6 (25.8 to 29.4)) (p = 0.32). Conclusions: Testing olfactory function may be helpful in differentiating vascular parkinsonism from Parkinson’s disease.

Platelet degranulation and monocyte-platelet complex formation are increased in the acute and convalescent phases after ischaemic stroke or transient ischaemic attack.

Flow cytometric studies suggest that platelets are activated in ischaemic stroke or transient ischaemic attack (TIA). However, few studies have measured circulating leucocyte–platelet complexes in this patient population. Whole blood flow cytometry was used to quantify the expression of CD62P‐, CD63‐, and PAC1‐binding, and the percentages of leucocyte–platelet complexes in acute (1–27 d, n = 79) and convalescent (79–725 d, n = 70) ischaemic cerebrovascular disease (CVD) patients compared with controls without CVD (n = 27). We performed a full blood count, and measured plasma levels of soluble P‐selectin, soluble E‐selectin, and von Willebrand factor antigen (VWF:Ag) as additional markers of platelet and/or endothelial cell activation. The median percentage CD62P expression and the median percentage monocyte–platelet complexes were higher in both acute and convalescent CVD patients than controls (P ≤ 0·02). The mean white cell count and mean VWF:Ag levels were significantly elevated in the acute and convalescent phases after ischaemic stroke or TIA (P ≤ 0·02). Otherwise, there was no significant increase in any other marker of platelet or endothelial activation in CVD patients. There was a positive correlation between the percentage expression of CD62P and the percentages of both neutrophil–platelet and monocyte–platelet complexes in the acute phase, and the percentages of all leucocyte–platelet complexes in the convalescent phase after ischaemic CVD. This study provides evidence for ongoing excessive platelet and/or endothelial activation in ischaemic CVD patients despite treatment with antithrombotic therapy.

Olfaction differentiates parkin disease from early-onset parkinsonism and Parkinson disease

The authors studied whether olfactory dysfunction is present in parkin disease using the University of Pennsylvania Smell Identification Test (UPSIT). The mean UPSIT score in parkin patients was 27.3 (95% CI 24.4 to 30.2). This did not differ from the normal group mean of 29.4 (95% CI 28.0 to 30.7; p = 0.22) but was higher than the Parkinson disease group (mean 14.3; 95% CI 12.2 to 19.5; p < 0.0001) and the parkin-negative group (mean 17.1; 95% CI 14.8 to 16.3; p < 0.0001) values. Parkin disease may be a distinct and separate entity from Parkinson disease.