DIABETES OBESITY & METABOLISM, Issue 2 2001
C. J. De Souza
SUMMARY Aim Abnormal ,-cell function, characterized as the inability of the ,-cell to mount a rapid secretory response to glucose, is a well-established pathology of type 2 diabetes mellitus. These studies were designed to demonstrate the importance of early insulin release on the control of meal-induced glucose excursions by capitalizing on the significant pharmacodynamic differences between several oral insulin secreting agents. Methods Male Sprague Dawley fitted with indwelling jugular cannulas were used to compare the pharmacodynamic profiles of nateglinide (Nateg), glipizide (Glip) and repaglinide (Repag) through frequent blood samples following the administration of these compounds via oral gavage. In similar animals which were pretrained to consume their daily food intake in two discrete 45-min meals, the effects of compound induced changes in pre-meal, meal and post-meal insulin profiles on glycaemic control were assessed through frequent blood sampling following the administration of these compounds 10 min prior to a 30-min meal. Results There were significant pharmacodynamics differences between the three oral agents tested and the time to elicit peak insulin secretory responses increased from Nateg (4 min) to Repag (10 min) to Glip (45 min). During the meal tolerance test, glibenclamide did not increase pre-meal insulin levels and glucose excursions paralleled those in the control. Conversely, the other three agents, at doses that produced hypoglycaemic responses of similar magnitude, all increased early insulin release (,AUC(-15 to 3 min) = 0.5 ± 0.01, 1.6 ± 0.4, 3.6 ± 0.0, 1.2 ± 0.1 and 1.73 ± 0.4 nmol/min, for control, Nateg at 60 and 120 mg/kg, Glip and Repag, respectively) and curbed glucose excursions during the meal at varying rates and degrees (,AUC(0,30 min) = 39 ± 6, 8 ± 7, 5 ± 7, ,,1 ± 8 and ,,3 ± 8 mmol/min for control, Nateg at 60 and 120 mg/kg, Glip and Repag, respectively). However, unlike Nateg, the longer duration of action of Repag and Glip elicited sustained post-meal relative hypoglycaemia. Conclusion These data support the impact of early and rapid insulin release in the control of prandial and post-meal glycaemia and demonstrate that a short anticipatory burst of insulin, restricted to the beginning of a meal, provides a clear metabolic advantage and prevents post-meal hypoglycaemic episodes when compared to a greater but reactive insulin exposure that follows a meal-induced increase in glucose excursion. [source]

Cardiac Allograft Remodeling After Heart Transplantation Is Associated with Increased Graft Vasculopathy and Mortality

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009
E. Raichlin
The aim of this study was to assess the patterns, predictors and outcomes of left ventricular remodeling after heart transplantation (HTX). Routine echocardiographic studies were performed and analyzed at 1 week, 1 year and 3,5 years after HTX in 134 recipients. At each study point the total cohort was divided into three subgroups based on determination of left ventricle mass and relative wall thickness: (1) NG,normal geometry (2) CR,concentric remodeling and (3) CH,concentric hypertrophy. Abnormal left ventricular geometry was found as early as 1 week after HTX in 85% of patients. Explosive mode of donor brain death was the most significant determinant of CH (OR 2.9, p = 0.01) at 1 week. CH at 1 week (OR 2.72, p = 0.01), increased body mass index (OR 1.1, p = 0.01) and cytomegalovirus viremia (OR , 4.06, p = 0.02) were predictors of CH at 1 year. CH of the cardiac allograft at 1 year was associated with increased mortality as compared to NG (RR 1.87, p = 0.03). CR (RR 1.73, p = 0.027) and CH (RR 2.04, p = 0.008) of the cardiac allograft at 1 year is associated with increased subsequent graft arteriosclerosis as compared to NG. [source]

Abnormal Endothelial Tight Junctions in Active Lesions and Normal-appearing White Matter in Multiple Sclerosis

BRAIN PATHOLOGY, Issue 2 2002
Jonnie Plumb
Blood-brain barrier (BBB) breakdown, demonstrable in vivo by enhanced MRI is characteristic of new and expanding inflammatory lesions in relapsing-remitting and chronic progressive multiple sclerosis (MS). Subtle leakage may also occur in primary progressive MS. However, the anatomical route(s) of BBB leakage have not been demonstrated. We investigated the possible involvement of interendothelial tight junctions (TJ) by examining the expression of TJ proteins (occludin and ZO-1) in blood vessels in active MS lesions from 8 cases of MS and in normal-appearing white (NAWM) matter from 6 cases. Blood vessels (10,50 per frozen section) were scanned using confocal laser scanning microscopy to acquire datasets for analysis. TJ abnormalities manifested as beading, interruption, absence or diffuse cytoplasmic localization of fluorescence, or separation of junctions (putative opening) were frequent (affecting 40% of vessels) in oil-red-O-positive active plaques but less frequent in NAWM (15%), and in normal (<2%) and neurological controls (6%). Putatively "open" junctions were seen in vessels in active lesions and in microscopically inflamed vessels in NAWM. Dual fluorescence revealed abnormal TJs in vessels with pre-mortem serum protein leakage. Abnormal or open TJs, associated with inflammation may contribute to BBB leakage in enhancing MRI lesions and may also be involved in subtle leakage in non-enhancing focal and diffuse lesions in NAWM. BBB disruption due to tight junctional pathology should be regarded as a significant form of tissue injury in MS, alongside demyelination and axonopathy. [source]

Abnormal respiratory-related evoked potentials in untreated awake patients with severe obstructive sleep apnoea syndrome

CLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 1 2009
Christine Donzel-Raynaud
Summary Aim:, Obstructive sleep apnoeas generate an intense afferent traffic leading to arousal and apnoea termination. Yet a decrease in the sensitivity of the afferents has been described in patients with obstructive sleep apnoea, and could be a determinant of disease severity. How mechanical changes within the respiratory system are processed in the brain can be studied through the analysis of airway occlusion-related respiratory-related evoked potentials. Respiratory-related evoked potentials have been found altered during sleep in mild and moderate obstructive sleep apnoea syndrome, with contradictory results during wake. We hypothesized that respiratory-related evoked potentials' alterations during wake, if indeed a feature of the obstructive sleep apnoea syndrome, should be present in untreated severe patients. Methods:, Ten untreated patients with severe obstructive sleep apnoea syndrome and eight matched controls were studied. Respiratory-related evoked potentials were recorded in Cz-C3 and Cz-C4, and described in terms of the amplitudes and latencies of their components P1, N1, P2 and N2. Results:, Components amplitudes were similar in both groups. There was no significant difference in P1 latencies. This was also the case for N1 in Cz-C3. In contrast, N1 latencies in Cz-C4 were significantly longer in patients with obstructive sleep apnoea syndrome [median 98 ms (interquartile range 16·00) versus 79·5 ms (5·98), P = 0·015]. P2 and N2 were also significantly delayed, on both sides. Conclusions:, The cortical processing of airway occlusion-related afferents seems abnormal in untreated patients with severe obstructive sleep apnoea syndrome. This could be either a severity marker and/or an aggravating factor. [source]

Performance of the XE-2100 leucocyte differential

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 5 2002
G. Stamminger
Summary The XE-2100Ô was evaluated in a multicentre study following a previously established protocol. In this paper, we demonstrate the results of analytical performance studies, including comparison of the leucocyte differential with the NCCLS H20-A method and evaluation of flagging sensitivity. Linearity of the leucocyte count over a wide clinical range, low imprecision in clinically important ranges and no measurable carry over were confirmed. For comparability studies, 4 × 200 cell microscopic differential leucocyte counts were correlated with the automated five-part-differential counts. No significant differences were detected in (1) a group without morphological abnormality and in (2) a leukopenic group. The sensitivity of flags for the detection of immature granulocytes and myeloid blasts was very good. Only few samples containing blast cells remained unrecognized but these would have been examined microscopically in any event because of other abnormalities indicated by the instrument. Atypical/abnormal lymphocytes/and lymphoblasts were detected very reliably when the total lymphocyte count and the flags were evaluated in combination. A similiar procedure is recommended for the detection of left shift. When the neutrophil count is elevated, the sensitivity of the left shift flag is improved. The absolute immature granulocyte (IG) count by the instrument correlates well with that of myeloid precursor cells by microscopy. [source]

Pulmonary Function and Ventilatory Limitation to Exercise in Congenital Heart Disease

CONGENITAL HEART DISEASE, Issue 1 2009
Paolo T. Pianosi MD
ABSTRACT Pulmonary function in older children and adolescents following surgical repair of congenital heart disease is often abnormal for various reasons. Many of these patients report symptoms of exercise intolerance although the reason(s) for this symptom can be complicated and sometimes interrelated. Is it simply deconditioning due to inactive lifestyle, chronotropic or inotropic insufficiency? or could there indeed be ventilatory limitation to exercise? These are the questions facing the clinician with the increasing frequency of patients undergoing repair early in life and growing into adulthood. Understanding pulmonary functional outcomes and means of determining ventilatory limitation to exercise is essential to thoroughly address the problem. This article reviews pulmonary function in patients with congenital heart disease and then describes a newer technique that should be applied to determine ventilatory limitation to exercise. [source]

Decoding epithelial signals: critical role for the epidermal growth factor receptor in controlling intestinal transport function

ACTA PHYSIOLOGICA, Issue 1 2009
D. F. McCole
Abstract The intestinal epithelium engages in bidirectional transport of fluid and electrolytes to subserve the physiological processes of nutrient digestion and absorption, as well as the elimination of wastes, without excessive losses of bodily fluids that would lead to dehydration. The overall processes of intestinal ion transport, which in turn drive the secretion or absorption of water, are accordingly carefully regulated. We and others have identified the epidermal growth factor receptor (EGFr) as a critical regulator of mammalian intestinal ion transport. In this article, we focus on our studies that have uncovered the intricate signalling mechanisms downstream of EGFr that regulate both chloride secretion and sodium absorption by colonocytes. Emphasis will be placed on the EGFr-associated regulatory pathways that dictate the precise outcome to receptor activation in response to signals that may seem, on their face, to be quite similar if not identical. The concepts to be discussed underlie the ability of the intestinal epithelium to utilize a limited set of signalling effectors to produce a variety of outcomes suitable for varying physiological and pathophysiological demands. Our findings therefore are relevant not only to basic biological principles, but also may ultimately point to new therapeutic targets in intestinal diseases where ion transport is abnormal. [source]

Radiographic and Computed Tomographic Studies of Calcium Hydroxylapatite for Treatment of HIV,Associated Facial Lipoatrophy and Correction of Nasolabial Folds

DERMATOLOGIC SURGERY, Issue 2008
ALASTAIR CARRUTHERS MD
OBJECTIVES This study sought to assess the radiographic appearance produced by calcium hydroxylapatite soft tissue filler (CaHA; Radiesse, BioForm Medical Inc.) following augmentation to correct the nasolabial folds or facial wasting associated with human immunodeficiency virus lipoatrophy. METHODS A total of 58 patients, with either lipoatrophy or pronounced nasolabial folds, were treated with CaHA. Radiographic (X-ray) and computed tomographic (CT) imaging studies were conducted pre- and posttreatment in most patients; the images were sent to an independent laboratory to be analyzed by two evaluators who were board-certified radiologists and blinded to study purpose, product, and patient condition. RESULTS While results for X-ray evaluation showed inconsistencies in visualization of CaHA, CT scans showed consistent visualization in nearly all cases in patients who were imaged immediately after treatment. In addition, the results indicated no obscuration of underlying structures by CaHA and no evidence of CaHA migration. CONCLUSIONS Earlier clinical trials established CaHA as a safe and effective soft tissue filler. This CaHA study shows no overt radiographic safety concerns. CaHA is unlikely to be confused with conventional abnormal and adverse radiographic findings. The product is not always visible on X-ray. Although usually visible on CT scans, its appearance is distinct from surrounding bony structures and does not interfere with normal analysis. In addition, the product does not obscure underlying structures on CT scans. [source]

Neural tube defects and impaired neural progenitor cell proliferation in G,1 -deficient mice

DEVELOPMENTAL DYNAMICS, Issue 4 2010
Hiroaki Okae
Abstract Heterotrimeric G proteins are well known for their roles in signal transduction downstream of G protein,coupled receptors (GPCRs), and both G, subunits and tightly associated G,, subunits regulate downstream effector molecules. Compared to G, subunits, the physiological roles of individual G, and G, subunits are poorly understood. In this study, we generated mice deficient in the G,1 gene and found that G,1 is required for neural tube closure, neural progenitor cell proliferation, and neonatal development. About 40% G,1,/, embryos developed neural tube defects (NTDs) and abnormal actin organization was observed in the basal side of neuroepithelium. In addition, G,1,/, embryos without NTDs showed microencephaly and died within 2 days after birth. GPCR agonist-induced ERK phosphorylation, cell proliferation, and cell spreading, which were all found to be regulated by G,i and G,, signaling, were abnormal in G,1,/, neural progenitor cells. These data indicate that G,1 is required for normal embryonic neurogenesis. Developmental Dynamics 239:1089,1101, 2010. © 2010 Wiley-Liss, Inc. [source]

Comparative evaluation of human embryonic stem cell lines derived from zygotes with normal and abnormal pronuclei

DEVELOPMENTAL DYNAMICS, Issue 2 2010
Qing Huan
Abstract Human embryonic stem (hES) cell lines have been derived from normally or abnormally fertilized zygotes. However, the similar and different properties of these two types of hES cell lines are not well-known. To address this question, we generated nine hES cell lines from zygotes containing normal (2PN) and abnormal (0PN, 1PN, 3PN) pronuclei. A side-by-side comparison showed that all cell lines exhibited distinct identity and karyotypical stability. They expressed similar "stemness" markers and alkaline phosphatase activity and differentiated into three embryonic germ lineages in embryoid bodies and teratomas. Under neural differentiation-promoting conditions, they were directed into neural progenitors and neurons. However, a variation in cell cycle and the relative abundance of gene expression of undifferentiated and differentiated markers were observed. These variations were also seen among individually derived normal hES cell lines. Thus, normal hES cell lines can be developed from fertilized zygotes with abnormal pronuclei usually excluded from clinical use. Developmental Dynamics 239:425,438, 2010. © 2009 Wiley-Liss, Inc. [source]

Chondrocyte-specific Smad4 gene conditional knockout results in hearing loss and inner ear malformation in mice

DEVELOPMENTAL DYNAMICS, Issue 8 2009
Shi-Ming Yang
Abstract Smad4 is the central intracellular mediator of transforming growth factor-, (TGF-,) signaling, which plays crucial roles in tissue regeneration, cell differentiation, embryonic development, and regulation of the immune system. Conventional Smad4 gene knockout results in embryonic lethality, precluding its use in studies of the role of Smad4 in inner ear development. We used chondrocyte-specific Smad4 knockout mice (Smad4Co/Co) to investigate the function of Smad4 in inner ear development. Smad4Co/Co mice were characterized by a smaller cochlear volume, bone malformation, and abnormalities of the osseous spiral lamina and basilar membrane. The development of the hair cells was also abnormal, as evidenced by the disorganized stereocilia and reduced density of the neuronal processes beneath the hair cells. Auditory function tests revealed the homozygous Smad4Co/Co mice suffered from severe sensorineural hearing loss. Our results suggest that Smad4 is required for inner ear development and normal auditory function in mammals. Developmental Dynamics, 2009. © 2009 Wiley-Liss, Inc. [source]

Prefrontal gyral folding and its cognitive correlates in bipolar disorder and schizophrenia

ACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2009
A. M. McIntosh
Objective:, We sought to address whether dorsal or ventral prefrontal gyrification is abnormal in bipolar disorder and to determine its diagnostic specificity and cognitive associations. Method:, Forty-two out-patients with bipolar disorder, 28 with schizophrenia and 37 controls underwent magnetic resonance imaging. All subjects also underwent IQ and executive assessments using tasks whose performance has been localized to the ventral or dorsal prefrontal cortex. Cortical folding was quantified using the gyrification index (GI) and related to the cognitive measures. Results:, Patients with bipolar disorder showed reduced prefrontal gyrification compared with controls but did not differ from patients with schizophrenia. Neither ventral nor dorsal GI was preferentially affected in either disorder. Current IQ was positively and significantly correlated with GI. Conclusion:, Patients with bipolar disorder and patients with schizophrenia have reduced prefrontal gyrification affecting both ventral and dorsal subregions. These reductions were significantly associated with cognitive impairments occurring in both disorders. [source]

Attenuation of retinal vascular development and neovascularization in transgenic mice over-expressing thrombospondin-1 in the lens

DEVELOPMENTAL DYNAMICS, Issue 7 2006
Zhifeng Wu
Abstract Thrombospondin-1 (TSP1) is an endogenous inhibitor of angiogenesis and induces endothelial cell (EC) apoptosis. To study the role TSP1 plays during vascular development and neovascularization, we assessed the effects of ectopic TSP1 expression in the lens on retinal vascularization in transgenic mice. The TSP1 over-expressing mice showed abnormalities in the development of retinal vasculature. There was a dramatic decrease in the density of superficial and deep vascular plexuses of the retina in transgenic mice. The retinal vessels in TSP1 transgenic mice also appeared nonuniform and abnormal in maturation. We detected an increase in the number of EC undergoing apoptosis, which was compensated, in part, by an increase in cell proliferation in retinal vasculature of TSP1 transgenic mice. The TSP1 transgenic mice also exhibited increased levels of vessel obliteration and a limited preretinal neovascularization during oxygen-induced ischemic retinopathy (OIR). Our results indicate increased expression of TSP1 attenuates normal retinal vascularization and preretinal neovascularization during OIR. Therefore, modulation of TSP1 expression may provide an effective mechanism for regulation of ocular angiogenesis. Developmental Dynamics 235:1908,1920, 2006. © 2006 Wiley-Liss, Inc. [source]

Dorsal versus ventral scales and the dorsoventral patterning of chick foot epidermis

DEVELOPMENTAL DYNAMICS, Issue 3 2004
Fabrice Prin
Abstract The dorsal and ventral scales of the chick foot can be distinguished morphologically and molecularly: the dorsal oblong overlapping scuta expressing both , and , keratins, and the ventral roundish nonprotruding reticula expressing only , keratins. The question arises how En-1 and Lmx1, whose role in dorsoventral limb patterning has been well established, can affect skin morphogenesis, which occurs 8 to 12 days later. Forced expression of En-1 or of Lmx1 in the hindlimb have, respectively, as expected, a ventralizing or a dorsalizing effect on skin, leading to the formation of either reticula-type or scuta-type scales on both faces. In both cases, however, the scales are abnormal and even glabrous skin without any scales at all may form. The normal inductive interactions between dermis and epidermis are disturbed after En-1 or Lmx1 misexpression. Effectively, while Lmx1 endows the dermal precursors of the ventral region with scuta inducing ability, En-1 blocks the competence of the dorsal epidermis to build scuta. Developmental Dynamics 229:564,578, 2004. © 2004 Wiley-Liss, Inc. [source]

The clinical presentation of mitochondrial diseases in children with progressive intellectual and neurological deterioration: a national, prospective, population-based study

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 5 2010
CHRISTOPHER M VERITY
Aim, Our aim was to study the clinical presentation, mode of diagnosis, and epidemiology of mitochondrial disorders in children from the UK who have progressive intellectual and neurological deterioration (PIND). Method, Since April 1997, we have identified patients aged 16 years or younger with suspected PIND through the monthly notification card sent to all UK consultant paediatricians by the British Paediatric Surveillance Unit. Clinical details obtained from reporting paediatricians are classified by an Expert Group. Results, By July 2008, 2493 cases of PIND had been reported, among which there were 112 children (69 males, 43 females) with mitochondrial diseases presenting between birth and 14 years 7 months (median 12mo), divided into 13 subgroups. In some instances, clinical features were characteristic of mitochondrial disease, but many children presented non-specifically with combinations of developmental delay, hypotonia, failure to thrive, and seizures; 16 children had multisystem disease at presentation. Mortality was high: 40 children had died. Blood and/or cerebrospinal fluid lactate measurements were abnormal in 87 children, and 47 of 78 brain magnetic resonance images showed increased basal ganglia signal. Definite diagnoses were usually made by muscle enzyme or genetic studies. Interpretation, This is a unique population-based study of the mitochondrial disorders that cause childhood neurodegenerative disease. It provides detailed information about the clinical presentation and investigation of these complex cases. [source]

Smooth ocular pursuit in Chiari type II malformation

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2007
Michael S Salman MRCP PhD
Chiari type II malformation (CII) is a congenital anomaly of the cerebellum and brainstem, both important structures for processing smooth ocular pursuit. CII is associated with myelomeningocele and hydrocephalus. We investigated the effects of CII on smooth pursuit (SP) eye movements, and determined the effects of spinal lesion level, number of shunt revisions, nystagmus, and brain dysmorphology on SP. SP was recorded using an infrared eye tracker in 21 participants with CII (11 males, 10 females; age range 8-19y, mean 14y 3mo [SD 3y 2mo]). Thirty-eight healthy children (21 males, 17 females) constituted the comparison group. Participants followed a visual target moving sinusoidally at ± 10° amplitude, horizontally and vertically at 0.25 or 0.5Hz. SP gains, the ratio of eye to target velocities, were abnormal in the CII group with nystagmus (n= 8). The number of shunt revisions (range 0-10), brain dysmorphology, or spinal lesion level (n= 15 for lower and n= 6 for upper spinal lesion level) did not correlate with SP gains. SP is impaired in children with CII and nystagmus. Abnormal pursuit might be related to the CII dysgenesis or to effects of hydrocephalus. The lack of effect of shunt revisions and abnormal tracking in participants with nystagmus provide evidence that it is related primarily to the cerebellar and brainstem malformation. [source]

Interobserver reliability of visual interpretation of electroencephalograms in children with newly diagnosed seizures

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 5 2006
Hans Stroink MD
The reliability of visual interpretation of electroencephalograms (EEG) is of great importance in assessing the value of this diagnostic tool. We prospectively obtained 50 standard EEGs and 61 EEGs after partial sleep deprivation from 93 children (56 males, 37 females) with a mean age of 6 years 10 months (SE 5mo; range 4mo,15y 7mo) with one or more newly diagnosed, unprovoked seizures. Two clinical neurophysiologists independently classified the background pattern and the presence of epileptiform discharges or focal non-epileptiform abnormalities of each EEG. The agreement was substantial for the interpretation of the EEG as normal or abnormal (kappa 0.66), almost perfect for the presence of epileptiform discharges (kappa 0.83), substantial for the occurrence of an abnormal background pattern (kappa 0.73), and moderate for the presence of focal non-epileptiform discharges (kappa 0.54). In conclusion, the reliability of the visual interpretation of EEGs in children is almost perfect as regards the presence of epileptiform abnormalities, and moderate to substantial for the presence of other abnormalities. [source]

Developmental profiles for multiple object tracking and spatial memory: typically developing preschoolers and people with Williams syndrome

DEVELOPMENTAL SCIENCE, Issue 3 2010
Kirsten O'Hearn
The ability to track moving objects, a crucial skill for mature performance on everyday spatial tasks, has been hypothesized to require a specialized mechanism that may be available in infancy (i.e. indexes). Consistent with the idea of specialization, our previous work showed that object tracking was more impaired than a matched spatial memory task in individuals with Williams syndrome (WS), a genetic disorder characterized by severe visuo-spatial impairment. We now ask whether this unusual pattern of performance is a reflection of general immaturity or of true abnormality, possibly reflecting the atypical brain development in WS. To examine these two possibilities, we tested typically developing 3- and 4-year-olds and people with WS on multiple object tracking (MOT) and memory for static spatial location. The maximum number of objects that could be correctly tracked or remembered (estimated from the k -statistic) showed similar developmental profiles in typically developing 3- and 4-year-old children, but the WS profile differed from either age group. People with WS could track more objects than 3-year-olds, and the same number as 4-year-olds, but they could remember the locations of more static objects than both 3- and 4-year-olds. Combining these data with those from our previous studies, we found that typically developing children show increases in the number of objects they can track or remember between the ages of 3 and 6, and these increases grow in parallel across the two tasks. In contrast, object tracking in older children and adults with WS remains at the level of 4-year-olds, whereas the ability to remember multiple locations of static objects develops further. As a whole, the evidence suggests that MOT and memory for static location develop in tandem typically, but not in WS. Atypical development of the parietal lobe in people with WS could play a causal role in the abnormal, uneven pattern of performance in WS. This interpretation is consistent with the idea that multiple object tracking engages different mechanisms from those involved in memory for static object location, and that the former can be particularly disrupted by atypical development. [source]

Circulating adipocytokines in non-diabetic and Type 1 diabetic children: relationship to insulin therapy, glycaemic control and pubertal development

DIABETIC MEDICINE, Issue 6 2006
F. Celi
Abstract Aim To determine the influence of Type 1 diabetes mellitus on circulating adipocytokines in children. Methods The circulating concentrations of leptin, adiponectin, resistin and tumour necrosis factor (TNF)-, were measured in 91 children, aged 11.1 ± 2.7 years, with Type 1 diabetes mellitus (T1DM). Ninety-one healthy children were selected as control subjects. Results Body mass index-adjusted leptin concentrations were higher in the pubertal diabetic children compared with the control children. There was a significant positive correlation between leptin and daily insulin dose in the diabetic group. Circulating adiponectin concentrations were higher in the prepubertal diabetic children and were positively associated with HbA1c. Resistin concentrations were lower in the prepubertal non-diabetic subjects compared with the pubertal non-diabetic children, whose values were higher than those of the diabetic children. TNF-, concentrations were similar in non-diabetic and diabetic children. Conclusions Circulating concentrations of adipocytokines are abnormal in Type 1 diabetic children, although the direction of change differs by cytokine. Pubertal development, in addition to insulin treatment and glycaemic control, also influences the concentrations. [source]

The value of the Rydel-Seiffer tuning fork as a predictor of diabetic polyneuropathy compared with a neurothesiometer

DIABETIC MEDICINE, Issue 6 2004
T. Kästenbauer
Abstract Aims The aim of the study was to investigate the predictive value of the Rydel-Seiffer tuning fork for detecting diabetic neuropathy and to compare it with an electronic neurothesiometer. Methods In 2022 consecutive diabetic subjects, peripheral polyneuropathy was diagnosed by vibration perception threshold (VPT) at the tip of both great toes using a 128-Hz tuning fork and a neurothesiometer, by simple bedside tests and by the presence of neuropathic symptoms. These evaluations were further combined to diagnose peripheral nerve dysfunction (abnormal bedside tests) and symptomatic neuropathy. VPT was also measured in 175 non-diabetic control subjects to define normal values. Results VPT was normal in 1917 subjects and abnormal in 105 (5.2%) patients when measured by the tuning fork. Patients with an abnormal vibration test were significantly (P < 0.0001) older than subjects with a normal vibration sense, while diabetes duration and HbA1c of the former were also significantly elevated. The same was true for the percentages of an abnormal 10-g monofilament test (66.7% vs. 7.2%, P < 0.0001) and a missing Achilles' tendon reflex (68.6% vs. 24.8%, P < 0.0001). Finally, the VPT measured by the neurothesiometer was 2.5 times higher in patients with an abnormal tuning fork test (32.0 ± 9.8 vs. 12.5 ± 6.4 V, P < 0.0001). The plot of the difference of both methods against their mean yielded a good agreement of the two VPT measurements, and the tuning fork had a high sensitivity and positive predictive value for the diagnosis of abnormal bedside tests and for symptomatic neuropathy. Conclusion The tuning fork reliably detected peripheral neuropathy in comparison with the neurothesiometer. A tuning fork is a useful screening test for diabetic neuropathy. [source]

Endocervical curetting vs. endocervical brushing as case finding methods,

DIAGNOSTIC CYTOPATHOLOGY, Issue 5 2006
John A. Maksem M.D.
Abstract This paper focuses on the performance of endocervical curettage (ECC) and intensive endocervical brushing (ECB) (comprising two or more brushings of the endocervix with liquid-based cytology and cell-block examination) in the course of colposcopic examination for abnormal gynecological cytology. To assess their relative effectiveness in disease detection, we reviewed the outcomes of 1,824 colposcopic biopsy collections from women who had an index cytology diagnosis of LSIL or higher. Our intent was to gauge the relative success of ECC and ECB as case-finding procedures in relation to (1) the original cytological diagnosis and (2) the highest (most abnormal) histological diagnosis of the colposcopy study. Our purpose was to determine whether ECB could effectively replace ECC. One thousand five hundred and seven cases of LSILs or higher cases included an ECC along with two or more colposcopic biopsies and 317 cases included an ECB. ECBs were collected into a liquid fixative and processed as both cytology and cell-block specimens; whereas, ECCs were processed according to standard histological techniques. We found that intensive ECB recapitulates the highest diagnosis of the colposcopy study about 5,8 times as often as that of ECC. Moreover, when calculating the proportion of positive outcomes, we found that cases examined with biopsy and ECC discovered fewer women with CIN 2 or higher among both LSIL and HSIL index cytologies as compared with those of cases examined with biopsy and ECB (9.2% vs. 16.8% for LSIL and 63.7% vs. 72.2% for HSIL cases); and, more negative outcomes were seen among women evaluated with biopsy plus ECC than those with biopsy plus ECB (11.3% vs. 8.1% for LSIL and 4.7% vs. 1.4% for HSIL cases). Our findings suggest that the colposcopic study is optimized when it is performed in conjunction with ECB as opposed to ECC, and that intensive ECB may be superior to ECC. Diagn. Cytopathol. 2006; 34:313,316. © 2006 Wiley-Liss, Inc. [source]

Rapid review of liquid-based smears as a quality control measure

DIAGNOSTIC CYTOPATHOLOGY, Issue 3 2004
Sheryl Henderson M.Med.Sc.(Cytol.)
Abstract The objective of this study was to investigate the effectiveness of a standardized method of rapid review (RR) of monolayer preparations for the identification of abnormalities, the presence of an endocervical component and infectious agents. A total of 200 ThinPrep (Cytyc, Boxborough, MA) slides representing the spectrum of abnormalities commonly encountered in cervical/vaginal cytologic specimens was retrieved from archive. The study set comprised 129 cases within normal limits (WNL); 36 low-grade epithelial abnormalities (LGEA); 28 high-grade epithelial abnormalities (HGEA), including 2 endocervical adenocarcinomas in situ (AIS) and 7 carcinomas. Eighteen false negative (FN) cases were also included for study. Originally missed on initial review, these cases were found to be abnormal on quality control review (17 LGEA; 1 AIS). Commonly encountered infectious agents were represented and included Candida albicans, Trichomonas vaginalis, herpes simplex virus, and Actinomyces. The slides were reviewed using a standardized method of RR (turret technique, for 60 sec) by three experienced screeners masked to the original reference diagnosis. Median sensitivity for LGEA was 70% (range, 67,72%); HGEA, 69% (range, 54,80%); and FN, 65% (range, 56,78%). Specificity remained high, median specificity for LGEA was 95%; HGEA, 97%; and FN, 100%. There was no significant overcalling of any diagnostic category. The chi-square test at P < 0.05 showed no significant difference between RR and full manual rescreen of the ThinPrep smears in this study. While no statistical difference was proven, the sensitivity measurements for all categories of abnormality were moderate due to the high proportion of atypical cases included into the study set. Abnormalities on the monolayer preparations frequently displayed fewer, smaller groups of disaggregated cells with rounded cytoplasmic outlines that were difficult to discern on RR. Interobserver variation was noted. Monolayers with a paucity of diagnostic cells and those displaying subtle nuclear atypia were often overlooked. Diagn. Cytopathol. 2004;31:141,146. © 2004 Wiley-Liss, Inc. [source]

Outcome of floppy Nissen fundoplication with intraoperative manometry to treat sliding hiatal hernia

DISEASES OF THE ESOPHAGUS, Issue 4 2008
Y. Lei
SUMMARY., The aim of this study was to evaluate the effectiveness of floppy Nissen fundoplication with intraoperative esophageal manometry. Between February 1992 and July 2004, there were 102 patients with sliding hiatal hernia undergoing transabdominal Nissen fundoplication. They were divided into three groups: 27 patients were in the Nissen group (CNF), 44 in the floppy Nissen group (FNF, including 5 with laparoscopic Nissen fundoplication), and 31 in the intraoperative-esophageal-manometry group (INF, 13 with laparoscopic Nissen fundoplication). There were no operation-related deaths. Operation-related complications occurred in five patients within 1 month after operation: In CNF, two patients suffered from dysphagia and one from regurgitation; in FNF, one patient had slight dysphagia and two had regurgitation; in INF, there was no one who complained about dysphagia or regurgitation, but pneumothorax occurred in one case. After more than 2 years of follow-up, two patients, in CNF, suffered from severe dysphagia, one recurred and two with abnormal 24 h pH monitoring. In FNF, one patient had dysphagia, one recurred and three had abnormal 24 h pH monitoring; in INF, two patients had acid reflux on 24 h pH monitoring. The postoperative lower esophageal sphincter pressure was in the normal range in 30 of 31 patients (96.5%). The normal rate of postoperative tests in CNF, FNF and INF were 81.5%, 86.4% and 93.5%, respectively. Both the Nissen fundoplication and the floppy Nissen fundoplication are effective approaches to treat patients with sliding hiatal hernia. Intraoperative manometry is useful in standardizing the tightness of the wrap in floppy Nissen fundoplication and may contribute to reducing or avoiding the occurence of postoperative complications. [source]

Multichannel intraluminal impedance for the assessment of post-fundoplication dysphagia

DISEASES OF THE ESOPHAGUS, Issue 5 2006
T. Yigit
SUMMARY., Dysphagia often occurs after fundoplication, although its pathophysiology is not clear. We sought to better understand postfundoplication dysphagia by measuring esophageal clearance with multichannel intraluminal impedance (MII) along with more traditional work-up (manometry, upper gastrointestinal imaging [UGI], endoscopy). We evaluated 80 consecutive patients after laparoscopic fundoplication between April 2002 and November 2004. Patients were evaluated clinically and underwent simultaneous manometry and MII, 24-hour pH monitoring, endoscopy, and UGI. For analysis, patients were divided into the following groups based on the presence of dysphagia and fundoplication anatomy (by UGI/endoscopy): (1) Dysphagia and normal anatomy; (2) Dysphagia and abnormal anatomy; (3) No dysphagia and abnormal anatomy; and (4) No dysphagia and normal anatomy. Patients with dysphagia (Groups 1 & 2) had similar peristalsis (manometry), but were more likely to have impaired clearance by MII (32 pts, 62%) than those without dysphagia (9 pts, 32%, P = 0.01). Patients with abnormal anatomy (Groups 2 & 3) were also more likely to have impaired esophageal clearance (66%vs. 38%, P = 0.01). Finally, of patients that had normal fundoplication anatomy, those with dysphagia were much more likely to have impaired clearance (12 pts, 52%) than those with dysphagia (4 pts, 21%, P = 0.03). MII after fundoplication provides objective evidence of esophageal clearance, and is commonly abnormal in patients with abnormal fundoplication anatomy and/or dysphagia. Esophageal clearance is impaired in the majority of patients with postoperative dysphagia, even with normal fundoplication anatomy and normal peristalsis. MII may detect disorders in esophageal motility not detected by manometry. [source]

Histopathologic effects of neoadjuvant therapies for advanced squamous cell carcinoma of the esophagus: multivariate analysis of predictive factors and p53 overexpression

DISEASES OF THE ESOPHAGUS, Issue 1 2002
Y. Kajiyama
SUMMARY. In 97 patients (60, chemotherapy; 22, chemoradiotherapy; 15, radiotherapy), histopathologic effects were evaluated microscopically, and histologic response rates were compared among three neoadjuvant treatment modalities. Predictive factors for neoadjuvant therapies were analyzed by logistic regression, including the results of p53 immunohistochemical staining. In the chemoradiotherapy group, the pathologic response rate was 86.4%, and was significantly higher than that for chemotherapy (P < 0.0001) or for radiotherapy (P = 0.0031). In patients with normal p53 protein expression, the histopathologic response rate to chemotherapy was 20.0%, a higher rate than that for patients with abnormal p53 overexpression. In the chemoradiotherapy or radiotherapy group, however, the response rates were almost the same, irrespective of p53 oncoprotein status. From multivariate analysis, the neoadjuvant treatment modality itself was identified as the most powerful predictive factor for the effect. Chemoradiotherapy had the most powerful effect on advanced esophageal cancer, and p53 status did not influence the clinical outcome in this group. [source]

The magnocellular theory of developmental dyslexia

DYSLEXIA, Issue 1 2001
John Stein
Abstract Low literacy is termed ,developmental dyslexia' when reading is significantly behind that expected from the intelligence quotient (IQ) in the presence of other symptoms,incoordination, left,right confusions, poor sequencing,that characterize it as a neurological syndrome. 5,10% of children, particularly boys, are found to be dyslexic. Reading requires the acquisition of good orthographic skills for recognising the visual form of words which allows one to access their meaning directly. It also requires the development of good phonological skills for sounding out unfamiliar words using knowledge of letter sound conversion rules. In the dyslexic brain, temporoparietal language areas on the two sides are symmetrical without the normal left-sided advantage. Also brain ,warts' (ectopias) are found, particularly clustered round the left temporoparietal language areas. The visual magnocellular system is responsible for timing visual events when reading. It therefore signals any visual motion that occurs if unintended movements lead to images moving off the fovea (,retinal slip'). These signals are then used to bring the eyes back on target. Thus, sensitivity to visual motion seems to help determine how well orthographic skill can develop in both good and bad readers. In dyslexics, the development of the visual magnocellular system is impaired: development of the magnocellular layers of the dyslexic lateral geniculate nucleus (LGN) is abnormal; their motion sensitivity is reduced; many dyslexics show unsteady binocular fixation; hence poor visual localization, particularly on the left side (left neglect). Dyslexics' binocular instability and visual perceptual instability, therefore, can cause the letters they are trying to read to appear to move around and cross over each other. Hence, blanking one eye (monocular occlusion) can improve reading. Thus, good magnocellular function is essential for high motion sensitivity and stable binocular fixation, hence proper development of orthographic skills. Many dyslexics also have auditory/phonological problems. Distinguishing letter sounds depends on picking up the changes in sound frequency and amplitude that characterize them. Thus, high frequency (FM) and amplitude modulation (AM) sensitivity helps the development of good phonological skill, and low sensitivity impedes the acquisition of these skills. Thus dyslexics' sensitivity to FM and AM is significantly lower than that of good readers and this explains their problems with phonology. The cerebellum is the head ganglion of magnocellular systems; it contributes to binocular fixation and to inner speech for sounding out words, and it is clearly defective in dyslexics. Thus, there is evidence that most reading problems have a fundamental sensorimotor cause. But why do magnocellular systems fail to develop properly? There is a clear genetic basis for impaired development of magnocells throughout the brain. The best understood linkage is to the region of the Major Histocompatibility Complex (MHC) Class 1 on the short arm of chromosome 6 which helps to control the production of antibodies. The development of magnocells may be impaired by autoantibodies affecting the developing brain. Magnocells also need high amounts of polyunsaturated fatty acids to preserve the membrane flexibility that permits the rapid conformational changes of channel proteins which underlie their transient sensitivity. But the genes that underlie magnocellular weakness would not be so common unless there were compensating advantages to dyslexia. In developmental dyslexics there may be heightened development of parvocellular systems that underlie their holistic, artistic, ,seeing the whole picture' and entrepreneurial talents. Copyright © 2001 John Wiley & Sons, Ltd. [source]

An Echocardiographic Analysis of the Long-Term Effects of Carvedilol on Left Ventricular Remodeling, Systolic Performance, and Ventricular Filling Patterns in Dilated Cardiomyopathy

ECHOCARDIOGRAPHY, Issue 7 2005
Peter S. Rahko M.D.
Background: The long-term clinical benefit of beta blockade is well recognized, but data quantifying long-term effects of beta blockade on remodeling of the left ventricle (LV) is limited. Methods: This consecutive series evaluates the long-term response of the LV to the addition of carvedilol to conventional therapy for dilated cardiomyopathy. There were 33 patients who had a LV ejection fraction <45%, LV enlargement and symptomatic heart failure. Quantitative Doppler echocardiography was performed at baseline 6, 12, 24, and 36 months after initiation of carvedilol to evaluate LV ejection fraction, LV volume, wall stress, mass, regional function, and diastolic performance. Results: Compared to baseline there was a significant and sustained reduction in end-systolic volume and end-systolic wall stress with a corresponding improvement in LV ejection fraction. The LV mass did not decline but relative wall thickness increased toward normal. An analysis of regional wall motion responses showed an improvement in all areas, particularly the apical, septal, and lateral walls that was significantly more frequent in patients with a nonischemic etiology. Filling patterns of the LV remained abnormal throughout the study but changed with therapy suggesting a decline in filling pressures. These changes were sustained for 3 years. Conclusion: (1) The addition of carvedilol to conventional therapy for a dilated cardiomyopathy significantly improves LV ejection fraction and reduces LV end-systolic volume and wall stress for at least 3 years, (2) the response to 6 months of treatment predicts the long-term response, (3) the typical response is partial improvement of the LV, complete return to normal size, and function is uncommon, and (4) abnormalities of LV filling persist in virtually all patients throughout the course of treatment. [source]

Estimation of Global Left Ventricular Function from the Velocity of Longitudinal Shortening

ECHOCARDIOGRAPHY, Issue 3 2002
Dragos Vinereanu M.D., E.C., Ph.D.
Aims: To determine if global ventricular function can be assessed from the long-axis contraction of the left ventricle, we compared pulsed-wave Doppler myocardial imaging of mitral annular motion to radionuclide ventriculography. Methods and Results: We studied 51 patients (56 ± 10 years, 11 women) with a radionuclide ejection fraction of 52 ± 13% (15%,70%). Peak systolic velocities of medial and lateral mitral annular motion correlated with ejection fraction (0.55 and 0.54, respectively; P < 0.001), as did the time-velocity integrals (0.57 and 0.58, respectively; P < 0.001). Correlations were higher in normal ventricles (0.62,0.69) than in patients with previous myocardial infarction (0.39,0.64). Patients with anterior myocardial infarction had the lowest correlations (0.39,0.46). The best differentiation of normal (, 50%) from abnormal (< 50%) ejection fraction was provided by peak systolic velocity , 8 cm/sec for the medial (sensitivity 80%, specificity 89%) or lateral (sensitivity 80%, specificity 92%) mitral annulus. Conclusion: Global left ventricular function can be estimated by recording mitral annular velocity. The implementation of a cutoff limit of 8 cm/sec gave a simple guide for differentiating between normal and abnormal left ventricular systolic function that might be useful clinically in patients without regional wall-motion abnormalities. However, in patients with important segmental wall-motion abnormalities during systole, left ventricular longitudinal shortening is an imperfect surrogate for ejection fraction. [source]

Assessment of Elastic Properties of the Descending Thoracic Aorta By Transesophageal Echocardiography with Acoustic Quantification in Patients with a Stroke

ECHOCARDIOGRAPHY, Issue 8 2000
Seok-Min Kang M.D.
Previous studies have described the use of transesophageal echocardiography (TEE) with acoustic quantification (AQ) in assessing aortic elastic properties. We hypothesized that patients with a prior history of stroke (ST) may have a higher risk of atherosclerotic change in great vessels compared to nonstroke subjects (NST) and thus have decreased elastic properties. We assessed the elastic properties of the descending thoracic aorta (DTA) by TEE in ST patients and compared them with data in NST patients. Subjects included 31 with ST without any evidence of emboli originating from the heart (age 51 ± 10 years, M: F = 20: 11) and 25 age-matched NST (M: F= 8: 17). Patients with significant valvular heart disease including aortic and mitral regurgitation, left ventricular dysfunction (ejection fraction < 55%), and congenital heart disease were excluded. Compliance (C), distensibility (D), and stiffness index (SI) were measured using AQ and M-mode measurement at a level of the left atrium. We scored atherosclerotic risk factors (ARF) such as a history of diabetes, hypertension, smoking, hypercholesterolemia, and the presence of atheroma of DTA. There was no evidence of atheroma of DTA in NST. There were no significant differences in heart rate and systolic and diastolic blood pressure between ST and NST patients. Fractional area change (FAC) of DTA was significantly lower in ST than in NST patients (3.2 ± 1.6 vs 5.4 ± 2.5%, P= 0.000). ST patients had significantly lower C (1.2 ± 0.4 vs 1.5 ± 0.7 times 10 -3 cm2 mmHg -1, P= 0.039), lower D (0.8 ± 0.3 vs 1.5 ± 0.8 times 10 -3 mmHg -1, P= 0.000), and higher SI (10.3 ± 8.8 vs 5.3 ± 2.9, P= 0.006) than NST patients. ST patients without atheroma of DTA (n± 21) also had significantly lower C (1.1 ± 0.4 vs 1.5 ±0.7 times 10 -3 cm -2 mmHg -1, P= 0.038) and lower D (3.5 ± 1.4 vs 4.8 ± 2.4 times 10 -3 mmHg -1, P= 0.021) than NST patients. There was a significant positive correlation between SI and the score of ARF (r= 0.51, P= 0.000). The regional elastic properties of DTA measured by TEE with AQ and M-mode method were abnormal in ST. Therefore, TEE with AQ technique may have a possible clinical application for the detection of early atherosclerotic changes such as alteration of elastic properties in morphological normal DTA. [source]

Toxic responses of medaka, D-rR strain, to polychlorinatednaphthalene mixtures after embryonic exposure by in ovo nanoinjection: A partial life-cycle assessment

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2000
Sergio A. Villalobos
Abstract Polychlorinated naphthalenes (PCNs) are organic compounds with some chemical properties and uses similar to polychlo-rinated biphenyls. Polychlorinated naphthalenes have been detected in biota from certain aquatic environments. The toxicities of several PCN technical mixtures (Halowax) to medaka (Oryzias latipes) were determined by use of an embryo nanoinjection method. Medaka eggs (early gastrula) were injected with 0.5 nl of triolein (vehicle control) or 0.5 nl of four to five graded doses (0.3,30 ng/egg) of Halowax 1014, Halowax 1013, or Halowax 1051 in triolein. Following exposure, embryos developed, and fry were reared to sexual maturity (4 months), at which time they were euthanized. Responses were evaluated as early life stage (ELS) and early adult life stage (EALS) assessments. For ELS, lethality and sublethal alterations in embryos and larvae (<16 d old), such as craniofacial, cardiovascular, and myoskeletal deformities and abnormal or delayed hatch, were monitored for the first 9 d, and a dose severity index was computed. The EALS assessment examined the survival of 16-d-old larvae until early adulthood (123 ± 3 d old), including gonadosomatic index (GSI) and morphometry. Halowax 1014 was found to be the most toxic mixture (LD50 4.2 ng/egg), whereas Halowax 1013 and 1051 were significantly less toxic (LD50s could not be determined). The gonadosomatic index of females was significantly less in fish dosed with Halowax 1014 or 1051. The LD50 for medaka embryos nanoinjected with 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) is about 0.75 pg/egg. Thus, Halowax 1014 was 5,585-fold less potent than TCDD. For Halowax 1014, ELS assessments accurately predicted the results of EALS assessments. [source]