Neuropathology of familial tauopathy

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) is a hereditary progressive neurodegenerative disorder. FTDP‐17 was originally defined in Ann Arbor, Michigan, in 1996. Since then, more than 100 families with FTDP‐17 have been described throughout the world, including 18 families identified in Japan. Genetic studies have identified 40 different mutations in the microtubule‐associated protein tau (MAPT) gene. The clinical features of FTDP‐17 are characterized by behavioral, cognitive and motor disturbances that may occur in various combinations and degrees. Neuropathologic examination shows that various degrees of atrophy may be present in the frontal and temporal lobes, basal ganglia, amygdala and hippocampus. All the brains from patients with FTDP‐17 have also shown the presence of tau deposits in neurons and glial cells. Mutations in MAPT may result in the increased splicing of exon 10, leading to 4‐repeat tau depositions in both neurons and glial cells. MAPT mutations outside of exon 10 show 3‐ and 4‐repeat tau deposits, predominantly in neurons with less glial pathology. Neuronal pathology may resemble that of Alzheimer’s disease or Pick’s disease because of the presence of neurofibrillary tangles or Pick‐like bodies, whereas glial pathology may resemble that of progressive supranuclear palsy or corticobasal degeneration because of the presence of coiled bodies, tufted astrocytes or astrocytic plaques. Correlations between genetic mutations and the heterogeneity of clinical and neuropathologic features remain unclear.     

Infant and Neonatal Mortality for Primary Cesarean and Vaginal Births to Women with “No Indicated Risk,” United States, 1998–2001 Birth Cohorts

ABSTRACT: Background: The percentage of United States’ births delivered by cesarean section has increased rapidly in recent years, even for women considered to be at low risk for a cesarean section. The purpose of this paper is to examine infant and neonatal mortality risks associated with primary cesarean section compared with vaginal delivery for singleton full‐term (37–41 weeks’ gestation) women with no indicated medical risks or complications. Methods: National linked birth and infant death data for the 1998–2001 birth cohorts (5,762,037 live births and 11,897 infant deaths) were analyzed to assess the risk of infant and neonatal mortality for women with no indicated risk by method of delivery and cause of death. Multivariable logistic regression was used to model neonatal survival probabilities as a function of delivery method, and sociodemographic and medical risk factors. Results: Neonatal mortality rates were higher among infants delivered by cesarean section (1.77 per 1,000 live births) than for those delivered vaginally (0.62). The magnitude of this difference was reduced only moderately on statistical adjustment for demographic and medical factors, and when deaths due to congenital malformations and events with Apgar scores less than 4 were excluded. The cesarean/vaginal mortality differential was widespread, and not confined to a few causes of death. Conclusions: Understanding the causes of these differentials is important, given the rapid growth in the number of primary cesareans without a reported medical indication. (BIRTH 33:3 September 2006)     

Syntheses of radiolabeled ABT‐578 for ADME studies

Several isotopomers of ABT‐578 ( I , II , III , and IV ) were prepared starting from different labeled precursors: [5'‐³H]‐tetrazole ( 1 ), [5'‐¹⁴C]‐tetrazole ( 2 ), [40‐³H]rapamycin ( 3 ), and [2,11,31‐³H]rapamycin ( 4 ). It was shown that the tritium label at the 40 position of rapamycin is lost during an attempted synthesis of [40‐³H]ABT‐578 ( III ). Copyright © 2006 John Wiley & Sons, Ltd.     

Health‐related quality of life in multiple system atrophy

Although multiple system atrophy (MSA) is a neurodegenerative disorder leading to progressive disability and decreased life expectancy, little is known about patients' own evaluation of their illness and factors associated with poor health‐related quality of life (Hr‐QoL). We, therefore, assessed Hr‐QoL and its determinants in MSA. The following scales were applied to 115 patients in the European MSA‐Study Group (EMSA‐SG) Natural History Study: Medical Outcome Study Short Form (SF‐36), EQ‐5D, Beck Depression Inventory (BDI), Mini‐Mental state examination (MMSE), Unified MSA Rating Scale (UMSARS), Hoehn & Yahr (H&Y) Parkinson's disease staging scale, Composite Autonomic Symptom Scale (COMPASS), and Parkinson's Disease Sleep Scale (PDSS). Forty‐six percent of patients had moderate to severe depression (BDI ≥ 17); Hr‐QoL scores on the SF‐36 and EQ‐5D were significantly impaired. Pain, the only domain with similar scores in MSA and published PD patients, was reported more frequently in patients with MSA‐P (predominantly parkinsonian motor subtype) than MSA‐C (predominantly cerebellar motor subtype; 76% vs. 50%; P = 0.005). Hr‐QoL scores correlated most strongly with UMSARS motor, COMPASS, and BDI scores but not with MMSE scores, age at onset, or disease duration. The COMPASS and UMSARS activities of daily living scores were moderate‐to‐strong predictors for the SF‐36 physical summary score and the BDI and UMSARS motor scores for the SF‐36 mental summary score. This report is the first study to show that Hr‐QoL is significantly impaired in MSA. Although not all possible factors related to impaired Hr‐QoL in MSA could be assessed, autonomic dysfunction, motor impairment, and depression were most closely associated with poor Hr‐QoL, and therapeutic management, therefore, should concentrate upon these aspects of the disease. © 2006 Movement Disorder Society     

Association of diabetes-related emotional distress with diabetes treatment in primary care patients with Type 2 diabetes.

AIMS: To characterize the determinants of diabetes-related emotional distress by treatment modality (diet only, oral medication only, or insulin). METHODS: A total of 815 primary care patients with Type 2 diabetes completed the Problem Areas in Diabetes (PAID) Scale and other questions. We linked survey data to a diabetes clinical research database and used linear regression models to assess the associations of treatment with PAID score. RESULTS: PAID scores were significantly higher among insulin-treated (24.6) compared with oral-treated (17.8, P < 0.001) or diet-treated patients (14.7, P < 0.001), but not different between oral- vs. diet-treated patients (P = 0.2). Group scores remained similar, but the statistical significance of their differences was reduced and ultimately eliminated after sequential adjustment for diabetes severity, HbA(1c), body mass index, regimen adherence, and self-blood-glucose monitoring. Insulin-treated patients reported significantly higher distress than oral- or diet-treated patients on 16 of 20 PAID items. 'Worrying about the future' and 'guilt/anxiety when ... off track with diabetes' were the top two serious problems (PAID >or= 5) in all treatment groups. Not accepting diabetes diagnosis was a top concern for oral- and diet-treated patients, and unclear management goals distressed diet-treated patients. CONCLUSIONS: Primary care patients treated with insulin reported higher diabetes-related emotional distress compared with oral- or diet-treated patients. Greater distress was largely explained by greater disease severity and self-care burdens. To improve diabetes-specific quality of life, clinicians should address patients' sense of worry and guilt, uncertain acceptance of diabetes diagnosis, and unclear treatment goals.     

Fast decomposition of water and lipid using a GRASE technique with the IDEAL algorithm.

Three-point Dixon techniques achieve good lipid-water separation by estimating the phase due to field inhomogeneities. Recently it was demonstrated that the combination of an iterative algorithm (iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL)) with a fast spin-echo (FSE) three-point Dixon method yielded robust lipid-water decomposition. As an alternative to FSE, the gradient- and spin-echo (GRASE) technique has been developed for efficient data collection. In this work we present a method for lipid-water separation by combining IDEAL with the GRASE technique. An approach to correct for errors in the lipid-water decomposition caused by phase distortions due to the switching of the readout gradient polarities inherent to GRASE is presented. The IDEAL-GRASE technique is demonstrated in phantoms and in vivo for various applications, including pelvic, musculoskeletal, and (breath-hold) cardiac imaging.     

Impaired cardiovascular autonomic function in Parkinson's disease with visual hallucinations.

We assessed the relations of visual hallucinations (VH) to cardiovascular autonomic dysfunction in patients with Parkinson's disease (PD). The subjects were 37 patients without VH (VH(-)) and 31 with VH (VH(+)). Autonomic function was evaluated on the basis of cardiac 123-radioiodinated metaiodobenzylguanidine (123I-MIBG) uptake and hemodynamic testing with Valsalva maneuver. Systolic blood pressure (SBP) and plasma norepinephrine concentrations (NE) were measured by tilt-table testing. 123I-MIBG uptake was lower in VH(+) than VH(-). Hemodynamic studies showed that VH(-) had only cardiac sympathetic and parasympathetic dysfunction, while VH(+) additionally had reduced vasomotor sympathetic functions. The fall in SBP during tilt-table testing was greater in VH(+) than VH(-). NE and its difference in the supine and upright positions were decreased in VH(+). We conclude that cardiac and vasomotor sympathetic dysfunction is more severe in VH(+) than in VH(-). Severe dysfunction in PD with VH is probably attributed to Lewy-body lesions or neuronal loss in sympathetic ganglia, the central autonomic system, or both.     

Body composition in young female adults with Type 1 diabetes mellitus. A prospective case-control study.

AIMS: Overweight is common during late puberty in female patients with Type 1 diabetes. The aim of this study was to examine the change in body composition from late puberty to early adulthood in such female patients in comparison with age-matched control subjects. METHODS: Eighteen females with Type 1 diabetes and 19 healthy female control subjects were recruited for a case-control study at the age of 16-19 years (baseline). Six years later, 16 of the diabetic females and 17 of the control subjects were re-examined (follow-up). Body composition was assessed by dual energy X-ray absorptiometry. RESULTS: Body mass index (BMI) and fat mass index (total fat mass/height2) were significantly higher at baseline in the diabetic patients than in the control subjects (26.4 +/- 2.6 vs. 23.9 +/- 3.7 kg/m2, P < 0.05, and 10.0 +/- 2.4 vs. 8.0 +/- 2.8 kg/m2, P = 0.04, respectively). At follow-up, these parameters still tended to be higher in the diabetic group (27.8 +/- 4.9 vs. 24.6 +/- 5.7 kg/m2, P = 0.09, and 11.8 +/- 5.6 vs. 8.7 +/- 4.9 kg/m2, P = 0.05, respectively). BMI at baseline was strongly correlated to BMI at follow-up in both diabetic patients (r = 0.60; P < 0.05) and control subjects (r = 0.83; P < 0.01). CONCLUSIONS: Increased fat mass in pubertal girls with Type 1 diabetes seems to persist in young adulthood. This study emphasizes the need for new strategies to prevent the development of overweight during puberty in diabetic girls.     

Sub‐retinal neovascular membrane in exudative macular degeneration

Age‐related macular degeneration is a major cause of serious vision loss. The earliest stages of age‐related maculopathy may be defined by the size of the drusen present in the macula and the effects on vision. Further manifestations may include soft drusen, choroidal neovascularisation, macular haemorrhage and cicatricial or disciform degeneration of the macula. This report describes a patient with a macular haemorrhage, a choroidal neovascular membrane and serious loss of vision. In addition, the pathogenesis, diagnosis and treat‐ment options of macular degeneration are reviewed.