Age-matched Normal Control Subjects Research Articles

CFTR (TG)m(T)n polymorphism in patients with CBAVD in a population expressing low incidence of cystic fibrosis

As it is well established that an association exists between congenital bilateral absence of the vas deferens (CBAVD) and cystic fibrosis gene mutations, we investigated CFTR(TG)m(T)n polymorphism within a Taiwanese population that exhibits a very low incidence of CF. Sixty-three patients with CBAVD and 86 age-matched normal control subjects were evaluated. Temporal temperature gradient gel electrophoresis was used for CFTR mutational analysis. No major CFTR mutation was found in the patient series. A single prominent CFTR mutation, IVS8-5T, was present; however, (50.8% of 63 cases and 33.3% of 126 alleles), and exhibited a high prevalence of 12 or 13 TG repeats (93.8% of 32 cases and 95.2% of 42 alleles with IVS8-5T). Although these results are similar to those of Japanese CBAVD patients, they are higher than the common frequency (about 21%) found among Caucasian CBAVD patients. The very high percentage (42.9%) of patients with no CFTR mutations is also an ethnic characteristic. We concluded that CBAVD patients from Taiwan, who express a very low incidence of CF, were less affected by CFTR mutations, with the exception of IVS8-5T linked to either 12 or 13 TG repeats, which does exhibit a high prevalence among CBAVD patients tested.

Peripheral Vascular Endothelial Dysfunction in Glaucomatocyclitic Crisis: A Preliminary Study

Glaucomatocyclitic crisis (GCC) is a syndrome of recurrent unilateral increased intraocular pressure associated with mild cyclitis and few clinical symptoms. This study was undertaken to assess brachial artery endothelium-dependent flow-mediated vasodilation (FMD) as an indicator of vascular endothelial function, to describe the association between GCC and endothelial dysfunction excluding age effects. This prospective study was conducted from January 2007 to April 2009 and included 12 patients with GCC and 15 age-matched normal control subjects. Detailed clinical parameters were reviewed, including highly sensitive C-reactive protein (hs-CRP), homocysteine, anti-SSA, anti-cardiolipin antibodies, and HLA type. Brachial artery FMD and endothelium-independent, nitroglycerin-mediated vasodilation (NMD) were studied by using high-resolution, two-dimensional (2-D) ultrasonic imaging. Twelve patients with GCC were evaluated. The mean age of the patients was 36.3 years including 5 (41.6%) women and 7 (58.4%) men. There were no significant differences between patients with GCC and control subjects with regard to basal data, including body mass index, smoking, blood pressure, complete blood count, and routine blood biochemistries. Homocysteine and hs-CRP were within normal limits. Two (16.7%) patients were positive for HLA-B27, anti-SSA, and anti-cardiolipin antibodies. The nitroglycerin-mediated vasodilation in the patients with GCC was not significantly different from that of the control group. The FMD was much lower in the GCC group than in the control groups (mean 4.81% vs. 7.89%, P < 0.01). The significantly lower FMD in patients with GCC implies peripheral vascular endothelial dysfunction. However, in the 16.7% positive for the HLA-B27, anti-SSA, and anti-cardiolipin antibodies, these parameters are associated with GCC and abnormal FMD.

Model-Based Assessment of Cardiovascular Autonomic Control in Children with Obstructive Sleep Apnea

To quantitatively assess daytime autonomic cardiovascular control in pediatric subjects with and without obstructive sleep apnea syndrome (OSAS). Respiration, R-R intervals, and noninvasive continuous blood pressure were monitored in awake subjects in the supine and standing postures, as well as during cold face stimulation. Sleep disorders laboratory in a hospital setting. Ten pediatric patients (age 11.4 +/- 3.6 years) with moderate to severe OSAS (obstructive apnea-hypopnea index = 21.0 +/- 6.6/1 h) before treatment and 10 age-matched normal control subjects (age 11.5 +/- 3.7 years). Spectral analysis of heart rate variability revealed that high-frequency power was similar and the ratio of low- to high-frequency power was lower in subjects with OSAS vs control subjects. The closed-loop minimal model allowed heart rate variability to be partitioned into a component mediated by respiratory-cardiac coupling and a baroreflex component, whereas blood pressure variability was assumed to result from the direct effects of respiration and fluctuations in cardiac output. Baroreflex gain was lower in subjects with OSAS vs control subjects. Under orthostatic stress, respiratory-cardiac coupling gain decreased in both subject groups, but baroreflex gain decreased only in controls. The model was extended to incorporate time-varying parameter changes for analysis of the data collected during cold face stimulation: cardiac output gain increased in controls but remained unchanged in OSAS. Our findings suggest that vagal modulation of the heart remains relatively normal in pediatric subjects with OSAS. However, baseline cardiovascular sympathetic activity is elevated, and reactivity to autonomic challenges is impaired.

Homocysteine and cognitive impairment in Parkinson's disease: A biochemical, neuroimaging, and genetic study

The role of the plasma level of homocysteine (Hcy), as a primary outcome, and the effect of silent cerebrovascular lesions and genetic variants related to Hcy metabolism, as secondary outcomes, in the cognitive decline and dementia in Parkinson's disease (PD) were studied. This case-control study focused on 89 PD patients of minimum 10 years of evolution and older than 60 years, who were neuropsychologically classified either as cognitively normal (n = 37), having mild cognitive impairment (Petersen criteria) (n = 22), or suffering from dementia (DSM-IV) (n = 30), compared with cognitively normal age-matched control subjects (n = 30). Plasma levels of Hcy, vitamins B12 and B6, folic acid, polymorphisms in genes related to Hcy metabolism (MTHFR, MTR, MTRR, and CBS) and silent cerebrovascular events were analyzed. Plasma levels of Hcy were increased in PD patients (P = 0.0001). There were no differences between the groups of patients. The brain vascular burden was similar among PD groups. There was no association between polymorphisms in the studied genes and the Hcy plasma levels or cognitive status in PD patients. We found no evidence for a direct relationship between Hcy plasma levels and cognitive impairment and dementia in PD. No indirect effect through cerebrovascular disease or genetic background was found either.

Left Ventricular Systolic and Diastolic Dyssynchrony in Asymptomatic Hypertensive Patients

Diastolic and systolic dyssynchrony are common in patients with heart failure. However, the presence of dyssynchrony in asymptomatic patients with hypertension who are susceptible to the development of heart failure is not well understood. The aims of this study were (1) to evaluate the prevalence of systolic and diastolic dyssynchrony and (2) to identify the main determinants of left ventricular (LV) dyssynchrony in asymptomatic patients with hypertension. One hundred ten patients with hypertension consecutively enrolled were compared with 55 age-matched and gender-matched normal control subjects. Comprehensive echocardiography was performed, including conventional and Doppler tissue imaging parameters. LV end-systolic wall stress was calculated using a hemodynamic and echocardiographic M-mode data set. For the assessment of LV dyssynchrony, both the standard deviation of the time from QRS onset to peak systolic velocity and the maximal difference of the time from QRS onset to peak systolic velocity from 6 basal segments at the apical views were used and were compared between the two groups. Both systolic and diastolic dyssynchrony indexes were significantly higher in patients with hypertension than in the normal controls (P < .001), with no significant correlation between the systolic and diastolic dyssynchrony indexes. The proportions of patients with hypertension who had LV systolic and diastolic dyssynchrony were 24% and 21%, respectively. Multivariate analysis showed that the E/E' ratio (P < .001) was independently associated with LV systolic dyssynchrony, whereas LV mass index (P = .001) and E/E' (P < .001) were major determinants of LV diastolic dyssynchrony. LV systolic and diastolic dyssynchrony are not uncommon in asymptomatic patients with hypertension and are significantly associated with LV filling pressure. The determinants of LV systolic dyssynchrony are not the same as those of diastolic dyssynchrony, implying that different mechanisms are involved in the development of LV systolic and diastolic dyssynchrony in asymptomatic patients with hypertension.

Gait Analysis after Initial Nonoperative Treatment for Clubfeet: Intermediate Term Followup at Age 5

We conducted gait analysis following initial nonoperative clubfoot treatment to compare lower extremity kinematic (eg, ankle motion) and kinetic (eg, ankle power) characteristics between patients treated as infants with Ponseti casting or French physical therapy. This is a followup report of gait characteristics at age 5 years in patients who had previously been tested at age 2 years. One hundred-twenty five clubfeet in 90 patients (34 feet only Ponseti treatment, 40 only French PT, and 51 feet initial nonoperative treatment followed by surgery) were included. The gait characteristics were compared to those of age-matched normal control subjects. Ankle equinus during gait occurred in 5% of feet treated with the French method and none of those treated by the Ponseti method. Increased stance phase ankle dorsiflexion persisted in 24% of feet treated by the Ponseti method. Intoeing was seen in 1/3 of both the French and Ponseti methods. Ankle push-off power was decreased compared to normal in patients treated by both methods, and even more so in operated feet. The presence or absence of Achilles tenotomy did not affect ankle power. Gait characteristics of feet that did not have surgery and maintained correction were superior to those of operated feet.

Impaired myocardial oxidative metabolism in the remote normal region in patients in the chronic phase of myocardial infarction and left ventricular remodeling

BackgroundLeft ventricular (LV) remodeling occurs in the remote normal region in the LVs after myocardial infarction (MI) and is closely involved in heart failure. MethodsWe assessed myocardial oxygen consumption using a clearance rate constant Kmono for the time activity curves of 11C-acetate in 15 patients with a prior anterior wall MI, 8 with a prior inferior wall MI, and 10 age-matched normal control subjects. LV end-systolic volume index (ESVI) was determined by echocardiography. ResultsThe LVESVI was significantly greater in patients with an anterior and inferior MI than in control subjects. The heart rate systolic pressure product did not differ among the groups. Kmono in the remote normal region in patients with an anterior MI was significantly less than that in the corresponding area in control subjects (0.055 ± 0.005 vs 0.065 ± 0.008 min−1, P < .001). Kmono in the remote normal region in those with an inferior MI was also significantly less compared with controls (0.054 ± 0.007 vs 0.069 ± 0.010 min−1, P < .01). ConclusionIn patients with a prior MI and LV remodeling, myocardial oxidative metabolism is apparently impaired in the remote normal region where augmented myocardial energy production is needed against the increased end-systolic wall stress caused by LV dilatation.

Low serum BDNF and food intake regulation: A possible new explanation of the pathophysiology of eating disorders

Background Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays an important role in weight regulation and eating behavior, and poorly balanced diets lead to a decrease in blood BDNF levels. However, studies regarding BDNF blood levels in eating disorders (ED) have yielded inconsistent results. We measured serum concentrations of BDNF and assessed behavior and cognition related to eating in ED patients and control subjects. Methods Forty female drug-free patients [19 with anorexia nervosa (AN), 21 with bulimia nervosa (BN)], who did not meet the diagnostic criteria for depressive disorder, and 24 age-matched normal control subjects were enrolled in the current study. We evaluated eating-related psychopathology and depressive symptoms using the Eating Disorder Inventory-2 (EDI-2), Eating Attitude Test-26 (EAT-26) and the Hamilton Depression Rating Scale (HDRS), and measured serum BDNF levels by an enzyme-linked immunosorbent assay. Results Compared to normal controls, serum levels of BDNF were significantly reduced in AN, but not in BN. There was a significant positive correlation between serum BDNF levels and BMI in both AN patients ( r = .649, p = .003) and BN patients ( r = .626, p = .002). However, no correlation between serum BDNF levels and BMI was detected in the controls. Furthermore, there was a significant negative correlation between serum BDNF levels and the oral control subscale scores of EAT in both AN patients ( r = − .506, p = .027) and BN patients ( r = − .511, p = .018); whereas, no correlation was detected in normal controls. Conclusion Our study demonstrated that individuals showing more extreme food intake regulation were those with lower serum BDNF levels. This finding is contrary to that in mice where mice with reduced BDNF levels showed aberrant eating behavior. This result suggests that BDNF is no longer functioning appropriately in ED patients, which could be an important factor in the pathophysiological of ED.

Diffusion tensor tractography can predict hemiparesis in infants with high risk factors

Diffusion tensor tractography (DTT) is known to be useful in detecting white matter lesions. In the current study, we report on two hemiparetic patients with risk factors who showed abnormalities of the corticospinal tract (CST) on diffusion tensor tractography (DTT) prior to the manifestation of hemiparesis. Two hemiparetic patients with risk factors (preterm, low birth weight) and six age-matched normal control subjects were enrolled to this study. Diffusion tensor imaging (DTI) was performed at the age of 43 weeks (patient 1) and 33 weeks (patient 2) using 1.5-T with a Synergy-L Sensitivity Encoding (SENSE) head coil. We measured fractional anisotropy (FA), apparent diffusion coefficients (ADCs), and fiber counts of the CST. There were no definite asymmetric findings on physical examination and conventional brain MRI. By contrast, DTT showed a unilateral CST disruption at the periventricular white matter, low FA values, and low CST fiber counts compared with those of the unaffected CST and controls. These patients were diagnosed with hemiparetic cerebral palsy when we re-evaluated these patients at the age of 6 years (patient 1) and 3 years of age (patient 2), respectively. In these two patients, DTT revealed abnormalities of the CST prior to the manifestation of hemiparesis. Therefore, it seems that DTT would be a useful modality in detecting CST abnormalities in advance of clinical manifestation in infants with high risk factors.

Thrombophilia, Hypofibrinolysis, the eNOS T-786C Polymorphism, and Multifocal Osteonecrosis

We examined the hypothesis that thrombophilia, hypofibrinolysis, and the endothelial nitric oxide synthase (eNOS) T-786C polymorphism are common, potentially treatable, and similar pathophysiologic causes of multifocal (three sites or more) and unifocal (single-site) osteonecrosis. We prospectively evaluated twenty-six consecutively referred adults with multifocal osteonecrosis, who included thirteen with idiopathic multifocal osteonecrosis and thirteen with secondary multifocal osteonecrosis (resulting from steroid therapy in ten and alcoholism in three). We compared these patients with race, sex, and age-matched normal control subjects and with patients with idiopathic unifocal and secondary unifocal osteonecrosis, respectively. Using polymerase chain reaction and serologic measures, we studied thrombophilic and hypofibrinolytic mutations and the eNOS T-786C polymorphism. The total number of polymerase chain reaction and serologic thrombophilic-hypofibrinolytic abnormalities and the eNOS T-786C polymorphism did not differ between patients with idiopathic (p > 0.5) or secondary (p > 0.5) multifocal and unifocal osteonecrosis. The frequency of low free protein-S levels (<66%) in patients with secondary multifocal osteonecrosis (four of eleven patients) was higher than that in the control subjects (one of fifty-nine) (risk ratio = 21.5; 95% confidence interval, 2.6 to 174; p = 0.0016, Benjamini-Hochberg adjusted p [Bp] = 0.004). Factor-V Leiden heterozygosity was present in two of thirteen patients with secondary multifocal osteonecrosis compared with none of sixty-four control subjects (p = 0.027, Bp = 0.008). For eleven patients with secondary multifocal osteonecrosis, the eNOS T-786C polymorphism was present in nine of twenty-two alleles compared with eight of forty-four alleles in twenty-two normal control subjects (risk ratio = 2.3; 95% confidence interval, 1.0 to 5.0; p = 0.047, Bp = 0.016). The frequency of homocystinemia (>13.5 mumol/L) was higher in patients with idiopathic multifocal osteonecrosis (two of thirteen patients) than in normal controls (none of fifty-one) (p = 0.039, Bp = 0.004). A high level of factor VIII (>150%) was seen in four of eight patients with idiopathic multifocal osteonecrosis and in seven of forty-eight normal controls (risk ratio = 3.4; 95% confidence interval, 1.3 to 9.1; p = 0.04, Bp = 0.008). The eNOS T-786C mutant allele was present in seven of twelve alleles in the six patients with idiopathic multifocal osteonecrosis who were tested, compared with twenty-five of 108 alleles in fifty-four control subjects (risk ratio = 2.5; 95% confidence interval, 1.4 to 4.5; p = 0.015, Bp = 0.008). Limited by the small numbers of patients with multifocal osteonecrosis, this exploratory study suggested that thrombophilia was associated with both idiopathic multifocal osteonecrosis and secondary multifocal osteonecrosis, as was the eNOS T-786C polymorphism. Multifocal and unifocal osteonecrosis are similarly associated with thrombophilia, hypofibrinolysis, and the eNOS T-786C polymorphism, which are potentially treatable pathophysiologic conditions, requiring further study.

Fusiform Function in Children with an Autism Spectrum Disorder Is a Matter of “Who”

Despite the importance of face processing for normal social development, no functional magnetic resonance imaging studies of face processing in autism have focused exclusively on the childhood years. To fill this gap, 45 children aged 6-12 participated in practice scans. After exclusion due to motion, 11 children with an ASD and 11 age-matched normal control subjects were included in final analyses. Stimuli consisted of pictures of a familiar adult, familiar child, stranger adult, stranger child, and objects. During the scan, children pressed a button in response to an identical face shown on two consecutive trials. On the basis of our prior research, masks of four anatomic regions of interest (ROIs) including the fusiform gyrus, amygdala, and anterior and posterior cingulate were created for each subject and manually edited for anatomic precision. Following deconvolution analyses, the number of voxels significantly active and percent signal change values that fell within each ROI mask were calculated for each subject. Analyses revealed normal fusiform activity in children with autism when viewing a face of their mother or other children. In contrast, looking at stranger adult faces initiated profound deficits in that the mean number of significantly active voxels in the fusiform bilaterally was approximately 25% of that shown in typically developing children. A selective fusiform deficit in response only to the faces of adult strangers may be the result of reduced attention and interest during those conditions. Face processing abnormalities found in autism beyond the fusiform likely exist.

Event-related synchronization of alpha activity in early Alzheimer's disease and mild cognitive impairment: An MEG study combining beamformer and group comparison

In patients with Alzheimer's disease (AD), it is sometimes challenging to identify typical findings in electroencephalography (EEG) or magnetoencephalography (MEG) such as a slowing of the posterior dominant activity or an increase in slow activity. In this MEG study, we evaluated the event-related synchronization (ERS) of alpha activity after eye closing in patients with early AD and mild cognitive impairment (MCI) who presented no slow MEG pattern. Thirteen patients with probable AD and thirteen patients with MCI, who met NINCDS-ADRDA and Petersen's diagnostic criteria, respectively, were enrolled. We also selected fourteen age-matched normal control subjects. MEG activity was acquired during eye-open and eye-closed states. The ERS after eye closing within 8-15Hz frequency band was calculated and its cortical source was superimposed on the individual's MRI by using the beamformer implemented in Brain Electrical Source Analysis (BESA). The Source image was converted into a standardized image, and group comparisons across patients with AD, MCI and controls were performed using BrainVoyager QX. The averaged ERS was observed dominantly in posterior regions in all three groups. Significant difference in ERS was observed only for the comparison between AD patients and controls, with AD patients showing increased ERS in frontal regions. Frontal shift of posterior alpha activity was observed clearly in AD patients using the combination of beamformer and group comparison.

Topographical Analysis of the Optic Nerve in Migraine Patients

Vascular dysfunction appears related to the development of migraines and has been associated with pressure-independent glaucoma. The purpose of this study is to investigate possible topographical differences in the optic nerve between migraine sufferers and normal age-matched control subjects. The identification of optic disc topographical differences between migraine and non-migraine sufferers may help clinicians determine if the presence of migraine influences the development and progression of glaucoma. Sixty consecutively seen patient-volunteers (30 subjects in migraine group: mean age 37.7 years, range from 19 to 66 years, 28 females and 2 males; 30 subjects in the control group: mean age 37.6 years, range from 19 to 61 years, 29 females and 1 male) were categorized as either migraine patients or control group subjects. All migraine subjects had been medically diagnosed with a migraine syndrome and were being treated with prophylactic medication. Optic nerve head topographical analysis was performed using a confocal scanning laser ophthalmoscope. The data was evaluated using generalized estimating equations, a priori and post hoc power analysis. No significant differences were found in any of the optic nerve parameters examined between the two groups. This study indicates that the optic nerve parameters as measured by the Heidelberg retinal tomograph II do not differ between migraine sufferers and age-matched control subjects.

Altered 8-oxoguanine glycosylase in mild cognitive impairment and late-stage Alzheimer's disease brain

Eight-hydroxy-2′-deoxyguanosine (8-OHdG) is increased in the brain in late-stage Alzheimer's disease (LAD) and mild cognitive impairment (MCI). To determine if decreased base-excision repair contributes to these elevations, we measured oxoguanine glycosylase 1 (OGG1) protein and incision activities in nuclear and mitochondrial fractions from frontal (FL), temporal (TL), and parietal (PL) lobes from 8 MCI and 7 LAD patients, and 6 age-matched normal control (NC) subjects. OGG1 activity was significantly ( P < 0.05) decreased in nuclear specimens of FL, TL, and PL in MCI and LAD and in mitochondria from LAD FL and TL and MCI TL. Nuclear OGG1 protein was significantly decreased in LAD FL and MCI and LAD PL. No differences in mitochondrial OGG1 protein levels were found. Overall, our results suggest that decreased OGG1 activity occurs early in the progression of AD, possibly mediated by 4-hydroxynonenal inactivation and may contribute to elevated 8-OHdG in the brain in MCI and LAD.

Quantitative Cerebrovascular Reserve Measured by Acetazolamide-Challenged Dynamic CT Perfusion in Ischemic Adult Moyamoya Disease: Initial Experience with Angiographic Correlation

CT perfusion is a much more readily accessible imaging method to assess cerebral hemodynamic status than single-photon emission CT. We prospectively assessed quantitative cerebrovascular reserve by using acetazolamide (ACZ)-challenged CT perfusion for evaluating hemodynamic impairment in ischemic adult Moyamoya disease and compared it with angiographic findings. Sixteen adult patients with ischemic Moyamoya disease and 12 age-matched normal control subjects underwent both ACZ-challenged CT perfusion and digital subtraction angiography. Normalized baseline hemodynamic parameters and their percent changes (PCs) were calculated in 56 hemispheres. We classified the degrees of distal carotid artery stenosis according to modified Suzuki stage and determined the presence of basal Moyamoya vessels (BMVs). The values of normalized parameters and their PCs were compared with angiographic findings. Normalized baseline mean transit time (MTT) and PC of normalized cerebral blood flow (CBF) were significantly correlated with angiographic stages in all of the vascular territories; however, the correlation coefficient of the normalized baseline MTT was lower than that of the PC of CBF. In the external borderzone and the middle cerebral arterial territory, the hemispheres with extensive BMVs exhibited significantly lower PC values of CBF and significantly higher normalized baseline MTT values than those in hemispheres with diminished BMVs and in normal control subjects. Among the hemodynamic parameters measured by ACZ-challenged CT perfusion, the PC of CBF correlated highly significantly with angiographic stage; however, the normalized baseline CT perfusion parameters showed weak or no significant correlation.

An aberrant protein complex in CSF as a biomarker of Alzheimer disease

To determine if an aberrant protein complex consisting of prostaglandin-d-synthase (PDS) and transthyretin (TTR) in CSF differentiates between subjects with Alzheimer disease (AD) and normal control (NC) subjects. Western blot analysis and a unique sandwich ELISA were used to quantify levels of complexed PDS/TTR in ventricular CSF of subjects with autopsy-verified diagnoses and in lumbar CSF of living subjects with mild to moderate probable AD and age-matched NC subjects. Ventricular CSF was obtained from short postmortem interval autopsies of 7 NC subjects (4 men/3 women), 12 diseased control (DC) subjects (7 men/5 women), 4 subjects with mild cognitive impairment (MCI) (2 men/2 women), and 8 subjects with late-stage AD (LAD) (4 men/4 women). Lumbar CSF was obtained from 15 subjects with probable AD (5 men/10 women) and 14 age-matched NC subjects (10 men/4 women) and was analyzed in a double-blind fashion. A significant increase in complexed PDS/TTR in ventricular CSF was found in MCI and LAD subjects but not DC subjects compared with NC subjects. Double-blind analysis of complexed PDS/TTR in lumbar CSF showed a significant sixfold increase in levels of the PDS/TTR complex in living probable AD subjects compared with age-matched NC subjects and a 100% sensitivity and 93% specificity in the identification of subjects with AD. After further study of larger numbers of patients, quantifying prostaglandin-d-synthase/transthyretin complex in CSF may be useful in the diagnosis of Alzheimer disease, possibly in the early stages of the disease.

Having One Kidney Does Not Accelerate the Rate of Development of Diabetic Nephropathy Lesions in Type 1 Diabetic Patients

Reduced nephron number is hypothesized to be a risk factor for chronic kidney disease and hypertension. Whether reduced nephron number accelerates the early stages of diabetic nephropathy is unknown. This study investigated whether the rate of development of diabetic nephropathy lesions was different in type 1 diabetic patients with a single (transplanted) kidney compared with patients with two (native) kidneys. Three groups of volunteers were studied: 28 type 1 diabetic kidney transplant recipients with 8-20 years of good graft function, 39 two-kidney patients with duration of type 1 diabetes matched to the time since transplant in the one-kidney group, and 30 age-matched normal control subjects. Electron microscopic morphometry was used to estimate glomerular structural parameters on 3.0 +/- 1.4 glomeruli per biopsy. In the one- versus two-kidney diabetic subject groups, respectively, serum creatinine (means +/- SD 1.3 +/- 0.4 vs. 0.9 +/- 0.2 mg/dl; P < 0.001), systolic blood pressure (133 +/- 13 vs. 122 +/- 11 mmHg; P < 0.001), and albumin excretion rate (median [range] 32.1 microg/min [2-622] vs. 6.8 microg/min [2-1,495]; P = 0.006) were higher. There were no differences in the one- versus two-kidney diabetic subject groups, respectively, in glomerular basement membrane width (median [range] 511 nm [308-745] vs. 473 nm [331-814]), mesangial fractional volume (mean +/- SD 0.30 +/- 0.06 vs. 0.27 +/- 0.07), mesangial matrix fractional volume (0.16 +/- 0.05 vs. 0.16 +/- 0.06), and mesangial matrix fractional volume per total mesangium (0.61 +/- 0.07 vs. 0.64 +/- 0.09). However, these glomerular structural parameters were statistically significantly higher in both diabetic subject groups compared with normal control subjects. Results were similar when patients receiving ACE inhibitors were excluded from the analyses. Reduced nephron number is not associated with accelerated development of diabetic glomerulopathy lesions in type 1 diabetic patients.

Both plasma retinol-binding protein and haptoglobin precursor allele 1 in CSF: Candidate biomarkers for the progression of normal to mild cognitive impairment to Alzheimer's disease

Cerebrospinal fluid (CSF) may be of valuable for exploring protein markers for the diagnosis of Alzheimer's disease (AD). The prospect of early detection and treatment, to slow progression, holds hope for aging populations with increased average lifespan. The aim of the present study was to investigate candidate CSF biological markers in patients with mild cognitive impairment (MCI) and AD and compare them with age-matched normal control subjects. In this report, we applied proteomics approaches to analyze 60 CSF samples derived from patients with neurodegenerative diseases such as MCI and AD. We classified patients by three groups: normal controls without cognitive dysfunction, MCI and AD. The AD group was subdivided into three groups by clinical severity according to clinical dementia rating (CDR), a well known clinical scale for dementia. We demonstrated a gradual decrease or absent of plasma retinol-binding protein (RBP) and haptoglobin precursor allele 1 in CSF from patients with MCI and AD compared to the age-matched normal subjects. Moreover, expression levels of both RBP and haptoglobin precursor allele 1 were observed to be very high in age-matched normal subjects. In contrast, the RBP and haptoglobin precursor allele 1 were much decreased in the MCI group; those expressions were more weak or absent in AD group, and correlated with disease severity and progression. These findings suggest that the CSF levels of both RBP and haptoglobin precursor allele 1 may be candidate biomarkers for the progression of normal to MCI to AD.

Association of Central Corneal Thickness and 24-hour Intraocular Pressure Fluctuation

To evaluate the association between office-hour central corneal thickness (CCT) and 24-hour intraocular pressure (IOP) fluctuation in patients with glaucoma. Observational case-control study. Measurements of IOP were obtained every 2 hours during a 24-hour period from 52 untreated glaucoma patients and 29 age-matched normal control subjects housed in a sleep laboratory. Habitual IOP measurements were obtained using a pneumatonometer in the sitting positions during the diurnal/wake period (7 AM to 11 PM) and in the supine position during the nocturnal/sleep period (11 PM to 7 AM). CCT was measured in all subjects using ultrasound pachymetry once during office hours. The association between IOP fluctuation (peak IOP-trough IOP) during the 24-hour period and the office-hour CCT was assessed in both glaucoma patients and healthy age-matched controls using Spearman rank order correlation. There was no statistically significant correlation between IOP fluctuation and CCT in glaucomatous (P=0.405) and normal subjects (P=0.456). Twenty-four-hour IOP fluctuations were not correlated with single CCT measurements taken during office hours in glaucoma patients.

Cerebral Oxygenation Monitoring for Detecting Critical Cerebral Hypoperfusion in Patients with Multiple System Atrophy during the Head-up Tilt Test

Near infrared spectroscopy (NIRS) is a non-invasive optical technique to monitor cerebral tissue oxygen saturation (ScO(2)). The purpose of this study was to reveal the usefulness of ScO(2) monitoring in evaluating cerebral circulation in patients with autonomic failure. Nineteen patients with multiple system atrophy (MSA), who had autonomic failure, and 10 age-matched normal control subjects participated. In addition to blood pressure monitoring, ScO(2) was recorded by a near-infrared spectroscopy instrument during head-up tilt (HUT) test. HUT tests induced postural symptoms in 9 MSA patients (presyncopal group), but not in 10 MSA patients (non-presyncopal group) or in any of the controls. ScO(2), which decreased slightly in the controls and MSA patients, did not differ significantly between the MSA and control groups. With regard to MSA subgroups, the ScO(2) reduction in the presyncopal group (-3.1+/-1.7%) was significantly larger than in the non-presyncopal group (-0.9+/-0.5%, P<0.005) and controls (-1.1+/-1.0%, P<0.05). The systolic blood pressure decreases during HUT in the non-presyncopal (-35.2+/-16.1 mmHg, P<0.01) and presyncopal (-54.3+/-27.5 mmHg, P<0.0005) groups were significantly greater than that in the control group (4.0+/-10.7 mmHg), but the difference between presyncopal and non-presyncopal groups was not significant. In our study, ScO(2) reduction seemed to be associated with presyncopal symptoms. ScO(2) monitoring may be useful to detect cerebral hypoperfusion in MSA patients with autonomic failure.