bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical mapping of nine Xq translocation breakpoints and identification of XPNPEP2 as a premature ovarian failure candidate gene
Authors: Prueitt R.L. , Ross J.L. , Zinn A.R.
Published: April 2003

Women with balanced translocations between the long arm of the X chromosome (Xq) and an autosome frequently suffer premature ovarian failure (POF). Two “critical regions” for POF which extend from Xq13→q22 and from Xq22→q26 have been identified using cytogenetics. To gain insight into the mechanism(s) responsible for ovarian failure in women with X;autosome translocations, we have molecularly characterized the translocation breakpoints of nine X chromosomes. We mapped the breakpoints using somatic cell hybrids retaining the derivative autosome and densely spaced markers from the X-chromosome physical map. One of the POF-associated breakpoints in a critical region (Xq25) mapped to a sequenced PAC clone. The translocation disrupts XPNPEP2, which encodes an Xaa-Pro aminopeptidase that hydrolyzes N-terminal Xaa-Pro bonds. XPNPEP2 mRNA was detected in fibroblasts that carry the translocation, suggesting that this gene at least partially escapes X inactivation. Although the physiologic substrates for the enzyme are not known, XPNPEP2 is a candidate gene for POF. Our breakpoint mapping data will help to identify additional candidate POF genes and to delineate the Xq POF critical region(s).
Chromosome mapping of RNF16 and Rnf16, human, mouse and rat genes coding for testis RING finger protein (terf), a member of the RING finger family
Authors: Ogawa S. , Saito T. , Matsuda Y. , Seki N. , Hayashi A. , Orimo A. , Hosoi T. , Ouchi Y. , Muramatsu M. , Hori T. , Inoue S.
Published: April 2003

RNF16 (ring finger protein 16; alias terf), a member of the RING finger family, has been shown to be exclusively expressed in the testis. Human RNF16 is located at 1q42 based on PCR-assisted analysis of both a human/rodent mono-chromosomal hybrid cell panel and a radiation hybrid-mapping panel. On the other hand, chromosomal mapping of the RNF16 gene by fluorescence in situ hybridization reveals that mouse Rnf16 is located at 11B1.2–B1.3 and rat Rnf16 at 10q22. These results provide additional evidence that the mouse 11B region displays conserved linkage homology with the rat 10q22 region, whereas in the case of RNF16, this homology is only conserved among rodents, distinct from the 1q42 region of the human genome.
Molecular cloning and characterization of a mouse homolog of human TNFSF14, a member of the TNF superfamily
Authors: Misawa K. , Nosaka T. , Kojima T. , Hirai M. , Kitamura T.
Published: April 2003

A member of the tumor necrosis factor (TNF) superfamily, human TNFSF14 (hTNFSF14)/HVEM-L (herpes virus entry mediator ligand) was isolated as a cellular ligand for HVEM/TR2 and human lymphotoxin β receptor (LTβR). TNFSF14 induces apoptosis and suppresses tumor formation. We have isolated a cDNA clone for a mouse homologue of hTNFSF14 by signal sequence trap (SST) screening which we recently developed. The deduced amino acid sequence of the mouse TNFSF14 (mTNFSF14) cDNA comprised 239 amino acid residues and was 77% identical to the hTNFSF14 protein. In Northern blot analysis, 2.1 kb and 4.2kb mTNFSF14 transcripts were detected in spleen and lung, and in heart, respectively. Fluorescence in situ hybridization analysis localized the mTNFSF14 gene Tnfsf14 to chromosome 17 which is tightly linked with Tnf, Lta, and Ltb.
Molecular cloning, chromosomal localization, and expression of the murine SALL1 ortholog Sall1
Authors: Buck A. , Archangelo L. , Dixkens C. , Kohlhase J.
Published: April 2003

SALL1 has been identified as one of now three human homologs of the region specific homeotic gene spalt (sal) of Drosophila, which encodes a zinc finger protein of characteristic structure. Mutations of SALL1 on chromosome 16q12.1 cause Townes-Brocks syndrome (TBS, OMIM no. 107480). In order to facilitate functional studies of this gene in a model organism, we searched for the murine homolog of SALL1. Here we report the genomic cloning, chromosome mapping, and partial expression analysis of the gene Sall1. Sequence comparison, Northern blot hybridization as well as the conserved chromosome location on the homologous mouse chromosome indicate that we have indeed isolated the murine homolog of SALL1.
Differential increase of steroid sulfatase activity in XX and XY trophoblast cells from human term placenta with syncytia formation in vitro
Authors: Ugele B. , Regemann K.
Published: April 2003

Steroid sulfatase (STS, EC 3.1.6.2) catalyzes the hydrolysis of the sulfate ester bonds of a variety of sulfated steroids, such as cholesterol, dehydroepiandrosterone, and estrone sulfate, a reaction influencing fertility and breast cancer in mammals. The activity of the enzyme is substantially elevated in placental syncytiotrophoblasts and is lower in other somatic cells. The polypeptide sequence of the enzyme is encoded by a gene located on the distal short arm of the human X chromosome. Prior studies have shown that the STS gene escapes X-chromosome inactivation. We studied the expression of the STS gene in primary cultures of cytotrophoblasts from human term placentae and compared it with the expression of autosomally encoded placental alkaline phosphatase (PALP) and X-linked glucose-6-phosphate dehydrogenase (G6PD). During 90 h in culture, the mononucleated cytotrophoblast cells did not proliferate, but differentiated into multinucleated, syncytiotrophoblast-like cells. STS activity in freshly isolated cytotrophoblasts was low (about 17%), compared to placental tis- sue, and about 1.7-fold higher in female than in male cells. During cultivation, STS activity increased 2- to 3-fold in female, but not in male, cells. PALP activity was very low in freshly isolated cytotrophoblasts (about 5% of placental tissue), and no significant difference between female and male cells was detectable. Within 90 h in culture, PALP activity increased in all preparations about 2- to 4-fold. G6PD activity in freshly isolated cytotrophoblasts showed great variation among preparations, and no significant difference between female and male cells was detectable. In both male and female cells the activity declined to about 50% of initial activity during cultivation. We conclude that human cytotrophoblasts in primary culture show a sex-specific regulation of STS activity, perhaps as a unique feature of the STS gene. The cytotrophoblast system may offer a new possibility to study the regulation of STS gene expression.
Expression and comparative chromosomal mapping of MKP-5 genes DUSP10/Dusp10
Authors: Masuda K. , Shima H. , Kikuchi K. , Watanabe Y. , Matsuda Y.
Published: April 2003

We have isolated a mouse cDNA for a novel MAPK phosphatase, designated as MKP-5. Two MKP-5 mRNA transcripts of 3.5 kb and 2.7 kb were detected. The 3.5-kb transcript was expressed in almost all the tissues examined, and was particularly abundant in cerebellum, skeletal muscle, and bone marrow. On the other hand, the 2.7-kb transcript was specifically and highly expressed in testis. The MKP-5 genes (DUSP10/Dusp10) were localized to chr 1q41, Chr 1H5 and chr 13q26 in human, mouse and rat, respectively. They were mapped in regions where conserved linkage homology has been identified among the three species.
Cerebral Cysticercotic Arteritis: Detection and Follow-Up by Transcranial Doppler
Authors: Cantú Carlos , Villarreal Jorge , Soto Jose Luis , Barinagarrementeria Fernando
Published: April 2003

Intracranial arteritis is a well-known complication of cerebral cysticercosis. The aim of this study was to explore the possible role of transcranial Doppler (TCD) in the evaluation of cysticercotic arteritis in 9 patients with subarachnoid cysticercosis and stroke. Arteritis of main basal vessels was detected by TCD in 7 of 10 arterial lesions that were demonstrated by cerebral angiography. The Doppler pattern was occlusive in 2 cases and stenotic in 5. In the 3 patients with lacunar infarcts, both cerebral angiography and TCD were normal. In 6 arterial lesions followed serially with TCD a stenotic pattern resolved within 4 and 6 months in 3 cases and remained in the stenotic range at 12 months in 1 case, whereas an occlusive pattern persisted at 6 and 18 months in the other 2 cases. In conclusion, TCD may be useful to detect and follow up cerebral vasculitis due to chronic cysticercotic arachnoiditis.
Cognitive Alterations in Non-Demented CADASIL Patients
Authors: Taillia H. , Chabriat H. , Kurtz A. , Verin M. , Levy C. , Vahedi K. , Tournier-Lasserve E. , Bousser M.G.
Published: April 2003

CADASIL is an inherited small-artery disease of the brain due to mutations of the Notch3 gene on chromosome 19. It is characterized by strokes, migraine with aura, and severe mood disturbances during mid adulthood and leads progressively to subcortical dementia. The precise onset of the cognitive decline in CADASIL remains unknown. We report here the cognitive evaluation of 8 non-demented symptomatic patients with CADASIL from 35 to 66 years of age. Altered performances were found in all subjects with the Wisconsin Card-Sorting Test (WCST), in 5/8 with the Trail-Making Test, and in 3/8 with copying of Rey’s figure. Altered performances with codes and similarities of the WAIS-R, the Wechsler Memory Scale, Raven’s Progressive Matrices, and the category and letter fluency task were observed less frequently (n ≤2). The score obtained with the WCST was not significantly correlated with the severity of the white-matter or basal ganglia signal abnormalities at MRI examination. Our data show that: (1) symptomatic CADASIL patients, although non-demented, can present with a subtle cognitive impairment; (2) tasks involving the frontal lobes are found most frequently altered, and (3) this subtle cognitive deficit can develop in the absence of major vascular events and does not appear to be correlated with the severity of brain lesions as seen at MRI examination.
Cysteinyl-Leukotriene Levels in Intracerebral Hemorrhage:An Edema-Promoting Factor?
Authors: Winking M. , Deinsberger W. , Joedicke A. , Boeker D.K.
Published: April 2003

In 12 operatively (stereotactic aspiration and recombinant tissue-type plasminogen activator, rTPA) and 5 conservatively treated patients with spontaneous intracerebral hemorrhage the amounts of cysteinyl-leukotriene (cys-LT) released by blood-brain cell contact were measured by the urinary excretion of their metabolites during treatment. The mean cys-LT release before treatment was 14.51 ± 1.13 pg/mg creatinine/ml hematoma volume. The urinary cys-LT excretion at the end of the measurements was significantly lower in the operatively treated group than in the patients with conservative therapy (p < 0.05). We also found a significant correlation between the perifocal edema volume and the amount of cys-LT measured in patients’ urine (p < 0.01). In an additional animal experiment using dissociated rat brain cells plasmin was excluded as an activator for cerebral cys-LT formation, which emphasizes that rTPA did not influence cys-LT formation.
Strokes in the Elderly – Higher Acute and 3-Month Mortality – An Explanation
Authors: Sharma Jagdish C. , Fletcher Sally , Vassallo Michael
Published: April 2003

Aim: Stroke is common in older people. The objective of the study was to determine if older stroke patients have a higher mortality and disability compared with younger patients for comparable stroke severity and pathology and whether there is an explanation for the difference. Methods: A prospective study was undertaken in 296 consecutive patients admitted with acute stroke. Patients were studied for neurological features, pre-stroke functional disability, severity of stroke defined by stroke syndromes and pathology of stroke on CT scans (202 patients). Post-stroke disability was defined according to the functional status within 72 h of admission. A record was made of the intercurrent illness while the patients were in acute wards and of the risk factors. Patients were dichotomised into two age groups: younger group – up to 75 years (163 patients) and older group – over 75 years (133 patients). Outcome was measured according to (1) discharge status from acute wards, i.e., dead or alive, and (2) mortality at 3 months. Results: Although there was no significant difference in severe clinical stroke syndromes (p = 0.72), CT scan features (p = 0.68) and pyrexia (0.38) between the two age groups, the older patients had significantly more disabling strokes as defined on Barthel Index (p = 0.015) and a higher mortality in the acute phase (p < 0.01) and at 3 months (p = 0.001). The older stroke patients had more severe pre-stroke disability (p < 0.001) and more severe neurological impairment for similar stroke severity and pathology. Early mortality was more influenced by pre-stroke global health than age whereas 3-month mortality was influenced by age to the exclusion of all other known prognostic factors. Conclusion: The older stroke patients have more disabling stroke and an increased mortality for a similar spectrum of stroke severity and pathology. The explanation for higher mortality of the older patients is the poor pre-stroke health and higher immediate post-stroke disability.
Aggravation of Acute Ischemic Stroke by Hyperthermia Is Related to an Excitotoxic Mechanism
Authors: Castillo José , Dávalos Antoni , Noya Manuel
Published: April 2003

Objective: To examine whether hyperthermia aggravates cerebral injury in acute ischemia by an excitotoxic mechanism, we studied the relationship between body temperature on admission and CSF concentrations of neuroexcitatory amino acids in 128 patients with acute ischemic stroke of less than 24 h duration. Methods: Stroke worsening was defined as the percent change between the Canadian Stroke Scale (CSS) at 48 h and the CSS on admission. Infarct volume was measured on days 4–7 on cranial computed tomography. Excitatory amino acids were analyzed using HPLC. Results: Glutamate concentration [median (min.-max.)] was 11 (2–19) µmol/l in hyperthermic patients (body temperature >37.5°C) and 5 (2–22) µmol/l in normothermic patients (p < 0.0001). Glycine concentration in hyperthermic and normothermic patients was 16 (3–21) µmol/l and 9 (3–50) µmol/l, respectively (p < 0.0001). Glutamate was significantly higher in patients with hyperthermia only during the first 12 h after the onset of symptoms. The CSF concentrations of glutamate (r = 0.52; p < 0.0001) and glycine (r = 0.62; p < 0.0001) correlated with body temperature. Body temperature was significantly related to stroke worsening and infarct size, but this effect was dependent on the glutamate effect. Conclusion: Glutamate and glycine release during the acute phase of cerebral ischemia could be responsible for the increased brain damage in hyperthermia.
Cardiac Papillary Fibroelastoma:A Rare Cause of Isch emic Stroke in the Young
Authors: Giannesini C. , Kubis N. , N’Guyen A. , Wassef M. , Mikol J. , Woimant F.
Published: April 2003

Among etiologies of stroke in young adults, primary cardiac tumors are very rare. We report the case of a 37-year-old woman who was admitted for an ischemic stroke in the right middle cerebral artery region. Etiologic investigations revealed, after transthoracic and transesophageal echocardiography, an aortic valve tumor. Treatment was first medical with anticoagulation, then surgical. Histological examination showed a papillary fibroelastoma. After a review of the literature, the possible mechanisms of the ischemic event are discussed and lead to the conclusion that this tumor must be surgically excised, even if asymptomatic, because of recurrent ischemic complications responsible for myocardial infarction, stroke and sudden death.
Small Centrum ovale Infarcts – A Pathological Study
Authors: Lammie G.A. , Wardlaw J.M.
Published: April 2003

There are limited data, mainly clinical and radiological, on small centrum ovale infarcts (SCOIs). From a consecutive series of 159 autopsy brains we identified 12 cases which on gross pathological examination harboured a total of 21 SCOIs. In the majority of lesions histology revealed a significant component of incompletely infarcted brain. Clinicopathological data suggested that the underlying mechanism was likely to have been cardioembolic in 3 cases, and possibly embolic from heart or aortic arch in a further 5. Two cases were due to ipsilateral carotid artery atheroma (i.e. 10 of 12 cases had possible embolic sources). The majority of lesions appeared to lie in arterial borderzones. The combined data suggest that SCOIs are pathologically and pathogenetically heterogeneous, and therefore that the term ‘lacune’ is inappropriate because this implies intrinsic small vessel disease as the underlying cause. Clinically, potentially treatable cardiac and large vessel pathology should be excluded.
Influence of Different Screening Procedures on the Stroke Prevalence Estimates: The Italian Longitudinal Study on Aging
Authors: Di Carlo Antonio , Candelise Livia , Gandolfo Carlo , Grigoletto Francesco , Volonnino Giuseppina , Baldereschi Marzia , Maggi Stefania , Scarlato Guglielmo , Amaducci† Luigi , Inzitari Domenico
Published: April 2003

Stroke prevalence surveys are more and more needed for health care and facility planning. Prevalence estimates and costs of the definition procedure may vary depending on different screening strategies. We evaluated the impact of these different strategies on the overall diagnostic procedure and on stroke prevalence estimates in the Italian Longitudinal Study on Aging. A population sample of 5,632 individuals aged 65–84 years was screened for stroke by a simple question on previous stroke diagnosis, questions on possible stroke symptoms and a simple neurological examination. Those screened positive by any of these procedures were fully examined by a neurologist for conclusive diagnosis. We determined the positive predictive value of each procedure on the final stroke diagnosis and calculated prevalence as if each procedure had been used separately. Using the three procedures combined, the prevalence rate was 6.0% (95% confidence interval, 5.4–6.7%). If each procedure had been used as the unique screening tool, the rates would have been 5.1% (4.5–5.7%), 4.1% (3.6–4.7%) and 2.3% (1.9–2.7%), and positive predictive values 66.4, 55.2 and 45.1%, respectively. Different screening procedures can affect stroke prevalence estimates. Compared to more complex screening strategies, the use of a simple question about previous diagnosis as the unique screening tool leads to only a slight underestimation of stroke prevalence and avoids a 66% increase in the number of subjects to be examined in a second-level specialist evaluation, potentially reducing the costs of the overall diagnostic procedure.
Temporary Occlusion of MiddleCerebral Artery by Macroembolism inCarotid Surgery
Authors: Claus S.P. , Louwerse E.S. , Mauser H.W. , van der Mee M. , Moll F.L. , Mess W.H. , Ackerstaff R.G.A.
Published: April 2003

Two patients are presented who during carotid endarterectomy (CEA) temporarily showed an obstruction of the middle cerebral artery (MCA) mainstem by a macroembolus resulting in cerebral ischaemia. Both cases are unusual examples of CEA and selected from a cohort of more than 1,500 operations. During surgery with general anaesthesia, brain function was monitored with computerized electroencephalography (EEG) and transcranial Doppler (TCD) ultrasonography. The simultaneous use of EEG and TCD monitoring allowed us to witness the development of intraoperative cerebral ischaemia and to relate these events to a temporary occlusion of the MCA mainstem by a macroembolus. This is the first life report that describes obstruction of a cerebral artery by arterial embolism resulting in cerebral ischaemia.
Accuracy of Initial Stroke Subtype Diagnosis
Authors: Kasner Scott E. , Kimmel Stephen E.
Published: April 2003

Background: The clinical diagnosis of stroke subtype is often inaccurate during the first 24 h after stroke onset. Several candidate diagnostic tests might be useful for early determination of subtype, but there is no consensus on what level of accuracy is required to be useful in the selection of patients for subtype-specific studies or therapies. Methods: A decision analysis was developed to explore the treatment options and estimate the requisite threshold of diagnostic accuracy. Four management strategies were considered: treat all (TA), treat based on new test (TBNT), treat based on clinical diagnosis (TBCD) and treat none (TN). Sensitivity analyses were performed over a wide range of the assumptions in the model. Results: The preferred treatment strategy was dependent on the probability and severity of adverse effects and the positive predictive value (PPV) of the proposed diagnostic test. For a potential therapy with infrequent (7.5%) but severe side effects, TN was preferable, but TBNT dominated if the PPV of the new test was at least 81%. For a therapy with frequent (25%) but mild adverse effects, TBNT was preferable. TA was favored for a therapy with infrequent and mild side effects and TN for a therapy with severe and frequent adverse events. TBCD was never the preferred option unless the PPV of the new test was less accurate than clinical diagnosis alone. Conclusions: Clinical diagnosis of stroke subtype is insufficient for patient selection, but a new diagnostic test with PPV ≥81% may be useful for early subtype diagnosis and patient selection for stroke subtype-specific clinical trials.
Transcranial Doppler Waveform Blunting in Severe Extracranial Carotid Artery Stenosis
Authors: Hartmann A. , Mast H. , Thompson J.L.P. , Sia R.M. , Mohr J.P.
Published: April 2003

Objective: To investigate the frequency of transcranial Doppler (TCD) waveform blunting in patients with severe (80–99%) symptomatic or asymptomatic extracranial carotid artery stenosis. Background: Severe carotid artery stenosis has been identified as a risk factor for ischemic stroke. Blunted Doppler flow waveforms (reduced systolic flow velocity and pulsatility) of the middle cerebral artery (MCA) are inferred to reflect hemodynamic impairment, possibly indicating an increased risk of stroke. Methods: The 114 consecutive patients (mean age 72.4 years, SD 9.0 years; 37% women; 46 clinically symptomatic, 68 asymptomatic) with 80–99% stenosis of the extracranial internal carotid artery (ICA), as determined by duplex sonography, were examined with TCD. Flow velocities, pulsatility index, and spectral waveforms of the MCA distal to the ICA stenosis were assessed blinded to the clinical status of the ICA: Doppler waveform blunting was defined as loss of the characteristic systolic peak. Odds ratios with 95% confidence intervals and χ2 statistics were used to describe the association between waveform blunting and the symptomatic status of the ICA stenosis. Results: Among symptomatic patients, 23 (50%) had completed strokes, and a further 23 (50%) had transient neurologic deficits in the territory of the stenotic ICA. Blunted spectral waveform was found in 37 (80%, 95% CI 68–92%) of the symptomatic and 25 (37%; 95% CI 25–49%) of the asymptomatic patients. Symptomatic patients had significantly increased odds of having blunted TCD waveforms (OR 7.5, 95% CI 3.1–18.1, p < 0.001). Conclusions: Our findings suggest that TCD waveform blunting in the MCA as here described may be an additional risk factor in the setting of severe extracranial carotid artery stenosis. A prospectively designed study to confirm our results seems warranted.
Intrathecal Release of Nitric Oxide and Its Relation to Final Brain Damage in Patients with Stroke
Authors: Tarkowski E. , Ringqvist Å. , Rosengren L. , Jensen C. , Ekholm S. , Wennmalm Å.
Published: April 2003

The potential role of inflammatory mechanisms in the pathophysiology of ischemic brain damage has intensely been discussed. We have recently demonstrated that stroke patients display an intrathecal production of proinflammatory cytokines early after onset of symptoms. IL-1β, one of these cytokines, stimulates the production of nitric oxide (NO), a potent inflammatory mediator. The aim of the present study was to investigate the intrathecal levels of nitrate, one of the main metabolites of NO in acute stroke and to relate its levels to brain damage. Stroke patients were prospectively studied with clinical evaluation, radiological assessment and analysis of intrathecal levels of nitrate by gas chromatography/mass spectrometry. In addition, simultaneous analyses of cytokines and of soluble Fas/APO-1 and bcl-2, two proteins regulating apoptosis, were performed. The intrathecal levels of nitrate were not significantly different in stroke patients compared to controls throughout the observation period. However, the intrathecal levels of nitrate increased significantly 3 months after stroke onset compared with the first 3 days. Interestingly, the levels of nitrate measured at stroke onset were negatively correlated to the final size of infarct volume (r = –0.69, p < 0.05) measured by MRI. In addition, patients with large infarcts displayed significantly (p = 0.008) lower levels of nitrate in cerebrospinal fluid compared to patients with small infarcts during the first 3 days after stroke onset. In contrast, the intrathecal levels of nitrate were significantly positively correlated (r = 0.79, p < 0.001) to the neurological deficit and negatively correlated (r = –0.76, p < 0.05) to bcl-2, a protein downregulating neuronal apoptosis, in the late stage of the stroke. Early NO production is associated with a smaller infarct volume, suggesting a protective effect, whereas late NO production is associated with severer neurological deficits, suggesting a neurotoxic effect. Treatment trials pertaining to modulate NO production in stroke should take into consideration the dual effect of NO on ischemic brain damage.
Are All Cardio-Embolic Strokes Embolic?
Authors: MacKenzie James M.
Published: April 2003

Estimates of the frequency of different types of ischaemic stroke vary widely, particularly those said to be of embolic aetiology. This retrospective autopsy study of 100 acute ischaemic strokes was undertaken to clarify the incidence of cardio-embolic stroke. Criteria for separating cardio-embolic from other forms of stroke were defined. Using these criteria, 26% of acute ischaemic strokes were cardio-embolic, 28% thrombotic, 12% atheromatous and the remainder due to various other causes including hypoperfusion with 11% being of undetermined aetiology. A significantly higher incidence of non-hypertensive cardiac disease was found in the group in whom no thrombus or thrombo-embolus was found at autopsy, suggesting that some of these strokes may have been due to unrecognised cerebral hypoperfusion. Haemodynamic stroke is probably an important and underrecognised form of acute ischaemic stroke.
Cerebral Microembolus Detection in an Unselected Acute Ischemic Stroke Population
Authors: Lund Christian , Rygh Jørgen , Stensrød Brynhild , Sandset Per Morten , Brucher Rainer , Russell David
Published: April 2003

Objective: The aims of this study were firstly to determine prevalence, frequency, and clinical significance of cerebral microemboli in an unselected acute ischemic stroke population and secondly to examine how this information may improve ischemic stroke subtype classification. Methods: We intended to perform transcranial Doppler (TCD) microembolus monitorings of the middle cerebral artery (MCA) in the symptomatic hemisphere for 45 min in 120 consecutive patients with internal carotid artery territory ischemia. The first examination was performed within 72 h from start of symptoms and the second 5 ± 1 days later. Platelet and coagulation system activation were measured following TCD monitoring in 38 patients. The strokes were subtyped using the TOAST classification criteria, and the patients’ clinical status was assessed at discharge using the Scandinavian Stroke Scale and the Barthel Index. Results: Microembolus monitoring was technically possible in 83 (69.2%) of the 120 patients. Thirty-two (26.6%) patients had an inadequate temporal bone acoustic window or were too restless to allow long-time monitoring. In 5 (4.2%) patients the relevant MCA was occluded. Twenty-two (26.5%) of the 83 patients had microemboli despite the fact that over 90% were receiving an antiplatelet or an anticoagulant treatment. The mean frequency of microemboli was 6.7 ± 13.6 per 45 min. Microemboli were more prevalent in assumed cardioembolic stroke than in other subtypes of ischemic stroke (p = 0.047). We found no association between the presence of cerebral microemboli and the clinical outcome or the parameters for platelet or coagulation system activation. The presence of microemboli was not associated with in-hospital deaths (p = 0.17), whereas MCA occlusion was (p = 0.01). Conclusions: Cerebral microemboli are frequent in unselected acute ischemic stroke patients despite antiplatelet or anticoagulant treatment. TCD detection of microemboli provides valuable pathophysiological information and may, therefore, improve current ischemic stroke subtype classification.
What Constitutes a True Hyperdense Middle Cerebral Artery Sign?
Authors: Koo C.K. , Teasdale Evelyn , Muir Keith W.
Published: April 2003

Objectives: The ‘hyperdense MCA sign’ refers to an appearance of increased attenuation of the proximal middle cerebral artery (MCA) that is often associated with thrombosis of the M1 MCA segment and may be the only diagnostic feature on computed tomography early after ischaemic stroke. False positives are recognized, and correct recognition of this sign has, therefore, assumed greater importance with the advent of thrombolytic therapy for stroke. We sought to define objective criteria for hyperdensity of the MCA. Methods: Brain computed tomographs obtained by a standard protocol in a neuroradiology department were analyzed by a single observer. All consecutive scans reported as exhibiting a hyperdense MCA were compared to controls reported as having normal scans. Ovoid regions of interest were placed over the vessels and cerebral cortices, and the attenuation in Hounsfield units (HU) measured. Absolute attenuation and ratios of one side to the other were compared. Results: MCA attenuation was unrelated to age in cases (n = 18) and controls (n = 80). The mean MCA attenuation was greater in the affected MCA of cases as compared with controls [54.0 HU (99% confidence interval CI 46.7–61.2) vs. 41.3 HU (99% CI 39.7–43.0); p < 0.00001]. Cases were subdivided into true and false positives by the ratio of denser:less dense MCA (within or without the 95% prediction interval for controls). In all true positives, the MCA ratio was > 1.2. 9 of 10 true positives had acute ischaemic stroke; 1 patient had herpes simplex encephalitis, but had MCA attenuation within the 95% CI for controls. False positives had mature cerebral infarction or non-ischaemic pathologies. The ratio of MCA attenuation to adjacent cerebral cortex was significantly higher in both true and false positives than in controls. Conclusions: Hyperdense MCAs associated with acute ischaemic stroke can be distinguished from normal vessels and false positives by measurement of absolute attenuation of affected and normal vessels: an absolute density of >43 HU and a MCA ratio of >1.2 defined hyperdensity and excluded all other pathologies. Confirmation in other centres is required.
A Cytogenetic Register of Down Syndrome in Lebanon
Authors: Zahed L. , Megarbane A.
Published: April 2003

Objectives: To provide data on the cytogenetics and epidemiology of Down syndrome in our community. Methods: All cases of Down syndrome diagnosed cytogenetically were entered over a period of 5 years together with data regarding age at referral, parental ages and parity. Results: A total of 280 cases were entered. In postnatal cases, the mean maternal age was 32.19 years and 41.5% of mothers were over 35 years. Only 47.3% of Down syndrome children were diagnosed at less than 1 month of age. The male to female sex ratio of 1.66 is significantly more elevated than that reported in larger registers. Conclusions: Because of problems inherent to Lebanon, this register does not have a high level of ascertainment, however it appears that the emphasis in a potential prevention programme should be placed on education, information and family planning.
Comparison of the Cariostatic Effects between Regimens to Administer Oolong Tea Polyphenols in SPF Rats
Authors: Ooshima T. , Minami T. , Matsumoto M. , Fujiwara T. , Sobue S. , Hamada S.
Published: April 2003

The cariostatic effect of oolong tea polyphenols administered according to several regimens was examined in specific pathogen-free (SPF) Sprague-Dawley rats given both a diet containing 20% sucrose and infected with S. sobrinus 6715. The crude preparation (OTE) of oolong tea polyphenols showed the most prominent effect on caries reduction in SPF rats when OTE was administered in the drinking water beginning 1 day prior to the inoculation of S. sobrinus 6715, when compared with chromatographically isolated polyphenol fractions (OTF1 and OTF6) of OTE. Reduction in caries development was found even when OTE was given 1 day after inoculation of the organism. OTE was shown to significantly inhibit dental caries in rats at the concentrations of either more than 5 μg/ml in drinking water or more than 10 μg/g in diet. OTF1 and OTF6 also showed significant inhibition of caries induction, with the minimum inhibitory concentration of OTF6 being 50 μg/ml in drinking water and the minimum inhibitory concentration of OTF1 being 100 μg/g in diet. These results indicate that cariostatic activity of OTE was effective even after the establishment of S. sobrinus in the oral cavity and was more effective in drinking water than in diet. Furthermore, OTE may contain some anticaries substances that affect the virulence of S. sobrinus other than glucosyltransferases.
Fluoride Concentration in Whole Saliva and Separate Gland Secretions in Schoolchildren after Intake of Fluoridated Milk
Authors: Twetman S. , Nederfors T. , Petersson L.G.
Published: April 2003

Fluoride concentration in whole saliva and in separate gland secretions was studied after a 7–day fluoridated milk regimen (1mg F per day) in 12 healthy schoolchildren aged 10–13 years. A 2–week fluoride–free run–in period preceded the tests in order to establish the endogenous baseline levels. Unstimulated and stimulated whole saliva and stimulated parotid and submandibular–sublingual saliva were collected at 1, 3, 6, 12 and 24h after F–milk ingestion, and fluoride concentrations were determined with an ion–selective electrode. Typical time–dependent excretion curves were obtained in all collected secretions. The fluoride levels were significantly elevated 1 and 3h in whole saliva and up to 6h in the gland secretions after intake of fluoridated milk when compared to baseline values. When acid–stimulated, the submandibular–sublingual glands were the major contributors of fluoride in the oral cavity. In conclusion, the results of this study demonstrate that fluoride ingested with milk is excreted through the salivary glands, indicating that the bioavailability of fluoride from milk equals that of other vehicles.
Efficacy of Sterilisation Methods and Their Effect on Enamel Demineralisation
Authors: Amaechi B.T. , Higham S.M. , Edgar W.M.
Published: April 2003

The aim of this project was to determine the effectiveness of sterilisation methods for dental enamel for use in intra–oral cariogenicity tests, and their possible effect on the degree of demineralisation of enamel. Bovine incisors were cut vertically into five portions and each assigned to one of five groups. Group 1 was used as a control while the other four groups were subjected, respectively, to gamma irradiation (≅25kGy), steam autoclaving (121°C for 15min), sodium hypochlorite (12% w/v for 24h) and povidone–iodine (7.5% w/v for 24h). Total viable counts of microorganisms remaining following sterilisation of the specimens were performed following incubation of the specimens for 24h at 37°C. Caries–like lesions were produced in each specimen using an acidic buffer solution (pH4.5). Sections were cut from each specimen, ground to 80–μm thickness, and microradiographed. Mineral loss and lesion depth were quantified using transverse microradiography. Statistical analysis was by ANOVA. Dunnett's and Tukey's tests. Microbial growth (Staphylococcus aureus and bacilli) was observed only in control specimens in both brain heart infusion broth and on blood agar plates. The sterilisation methods affected the enamel surface as follows: gamma irradiation (cream discolouration), NaOCl (bleaching), and povidone–iodine (white spot–like lesion). Compared with the control, there was no significant difference in mineral loss and lesion depth with any of the groups, but the numerical values of mineral loss and lesion depth in groups can be ranked as follows: gamma irradiation <povidone–iodine <control <autoclave <NaOCl. In conclusion, the four sterilisation methods were all effective to sterilise enamel, but gamma irradiation proved the most acceptable method for enamel to be used in cariogenicity tests having the least adverse effect.
Human Salivary Sugar Clearance after Sugar Rinses and Intake of Foodstuffs
Authors: Luke G.A. , Gough H. , Beeley J.A. , Geddes D.A.M.
Published: April 2003

The aetiology of dental caries is in part related to the retention time of dietary carbohydrates in the oral cavity and their subsequent metabolism by the oral bacteria. Salivary clearance of fermentable carbohydrates from three different foodstuffs was examined in 5 subjects and analyses performed by high–performance anion–exchange chromatography with pulsed amperometric detection. The clearance of glucose, fructose, sucrose, maltose and sorbitol rinses was studied as well as that of chocolate bars, white bread and bananas. Of the sugar rinses studied, sucrose was removed from saliva most rapidly whilst appreciable levels of sorbitol remained even after 1 h. Clearance of residual carbohydrates from bananas and chocolate bars seemed marginally faster than in the case of bread, but sucrose levels still tended to fall more quickly than other carbohydrates studied. Surprisingly, carbohydrate residues from the three foods studied were still present in the mouth even 1 h after ingestion, which is longer than has hitherto been reported.
Bacterial Counts in Carious Dentine under Restorations: 2–Year in vivo Effects
Authors: Weerheijm K.L. , Kreulen C.M. , de Soet J.J. , Groen H.J. , van Amerongen W.E.
Published: April 2003

Little is known about the long–term effects of fluoride–releasing materials on carious dentine in vivo. The aim was to investigate the 2–year influence of a resin–modified glass ionomer cement (RM–GIC) and amalgam on the bacteriological counts of carious dentine that remained under class I restorations. To enable a split–mouth design, 33 molar pairs in 33 patients (mean age 15.1 years, SD 1.4) were selected, based on clinically and radiographically diagnosed occlusal dentine caries. The enamel of the carious molars was removed, and the carious dentine was sampled under aseptic conditions just beneath the dentinoenamel junction. The molars were alternately restored with RM–GIC or amalgam without further removal of carious dentine. The samples were processed for microbiological determination of total viable counts (TVC), mutans streptococci (MS), and lactobacilli (LB). The molar pairs of 25 patients were reevaluated after 2 years using the same clinical techniques and were permanently restored after complete caries removal. Both materials showed a substantial decrease in numbers of TVC and LB of the carious dentine after the 2–year period. Compared to amalgam, the decrease in the numbers of LB was significantly more pronounced for RM–GIC. No microorganisms were detected in only 11 molars (6 RM–GIC and 5 amalgam) after the 2–year period. Based on this study, we suggest that complete removal of carious dentine is still the best conservative treatment, irrespective of the restorative material used.
Effects of Dental Treatment and Single Application of a 40% Chlorhexidine Varnish on Mutans Streptococci in Young Children under Intravenous Anaesthesia
Authors: van Maele D.M. , de Soet J.J. , Weerheijm K.L. , Groen H.J. , Veerkamp J.S.J.
Published: April 2003

Clinical studies suggest that application of a highly concentrated chlorhexidine varnish results in a decrease in the number of mutans streptococci and thereby a decrease in the caries risks. The aim of this study was to determine the effect of dental treatment on the levels of mutans streptococci (MS) and lactobacilli (LB) and the additional effect of a single application of 40% chlorhexidine varnish (EC40) on the level of MS. Twenty–three children under the age of 5 years scheduled for full dental treatment were selected. Of these 23 children (mean dmf–s 27.1, SD 19.3), 11 children had nursing bottle caries. The mean sugar exposure was 6.4. Subjects were randomly distributed into two groups of approximately equal size. One group received an EC40 application after dental treatment, while the other group received only full dental treatment, both with intravenous anaesthesia with propofol as a single drug. An unstimulated saliva sample and a plaque sample were taken prior to dental treatment. The saliva and plaque sampling of the subjects was repeated after 6 weeks. MS and LB were isolated and counted. The number of children harbouring more than 106 MS in a pooled plaque sample decreased significantly from 8 to 2 children 6 weeks after dental treatment. No additional effect of EC40 was found. The number of salivary MS did not change significantly between the groups or before and after treatment. The figures for LB remained at a high level of more than 104/ml saliva before (21 children) and 6 weeks after treatment (17 children). The results of this study indicate that dental treatment results in a significant suppression of plaque MS, while a single application of EC40 showed no significant additional suppression after 6 weeks.
A Randomised Controlled Trial of the Caries– Preventive Efficacy of a Chlorhexidine–Containing Varnish in High–Caries–Risk Adolescents
Authors: Forgie A.H. , Paterson M. , Pine C.M. , Pitts N.B. , Nugent Z.J.
Published: April 2003

A professionally applied two–stage chlorhexidine varnish, Chlorzoin®, was developed to achieve sustained release and minimise the problems of staining and bad taste associated with chlorhexidine mouthrinses. The primary aim of this randomised controlled clinical trial was to assess the efficacy of Chlorzoin in reducing the caries increment in high–caries–risk adolescents. Secondary aims included investigating the effect of compliance upon caries increment, the effect of Chlorzoin upon salivary mutans streptococci levels and assessing the benefit of individual dental health advice by dental auxiliaries in a community setting. 1,240 children, initially aged 11–13 years, assessed to be at high caries risk were recruited into the trial. The trial design involved four arms: an observational group, a control group, an active (Chlorzoin) varnish group and a placebo varnish group. All subjects were examined annually by a calibrated examiner who was blind to the group allocation. Three–year caries increments were calculated using clinical, clinical and fibre–optic transillumination, and clinical and bitewing data sets. The results indicated that the use of Chlorzoin had an initial effect on mutans streptococci levels but that no long–term reduction in caries increment or mutans streptococci infection could be detected. One reason for this lack of efficacy may have been the regimen of reduced frequency of varnish applications after the initial period. Children who followed the protocol and, therefore, were seen regularly by dental auxiliaries had a lower caries increment than those who did not. This finding was independent of varnish allocation. In summary, under this regimen, Chlorzoin has been found to be effective in decreasing salivary mutans streptococci but ineffective as a caries–preventive agent in high–risk Scottish children when applied pragmatically in a community setting.
An in vitro Comparison of the Ability of Fibre–Optic Transillumination, Visual Inspection and Radiographs to Detect Occlusal Caries and Evaluate Lesion Depth
Authors: Côrtes D.F. , Ekstrand K.R. , Elias-Boneta A.R. , Ellwood R.P.
Published: April 2003

The aim of this study was to compare the performance of fibre–optic transillumination (FOTI), visual inspection and bite–wing radiographs to detect occlusal caries and estimate the lesion depth. Fifty–nine extracted molars were assessed using FOTI and visual examination by 4 trained examiners and 1 examiner evaluated the bite–wing radiographs. Histological validation was performed using 250–μm sections examined with a stereomicroscope. For the three methods, the correlation between the lesion depth and the histological scores varied from 0.65 to 0.73. For dentinal caries detection, the areas under ROC curves ranged from 0.83 to 0.87. The radiographic method was poor at detecting lesions confined to enamel. FOTI, visual inspection and radiographs showed a good correlation with the histology but had difficulty in distinguishing lesions located deep in enamel or in the outer third of dentine. FOTI was shown to be as accurate as a detailed visual inspection in detecting occlusal caries.
Strain–Related Acid Production by Oral Streptococci
Authors: de Soet J.J. , Nyvad B. , Kilian M.
Published: April 2003

Acid production, in particular at low pH, is thought to be an important ecological determinant in dental caries. The aim of the present study was to determine the acid producing capability at different pH levels of 47 streptococcal strains, representing 9 species, isolated from human dental plaque. The bacteria were grown until mid log–phase under anaerobic conditions and acid production was measured in a pH–stat system at pH 7.0, 6.0, 5.5 and 5.0. At all pH values, the mean velocity of acid production (Vap) by Streptococcus mutans and S. sobrinus was significantly higher (p<0.01; ANOVA) than that of the other oral streptococci, including S. mitis, S. oralis, S. gordonii, S. sanguis, S. intermedius, S. anginosus, S. constellatus, and S. vestibularis. However, the Vap of some strains of S. mitis biovar 1 and S. oralis, particularly at pH values of 7.0 and 6.0, exceeded that of some strains of S. mutans. The Vap decreased with pH for all strains, but some strains of S. mitis biovar 1 and strains of the mutans streptococci maintained a relatively high rate of acid production. The results suggest that some strains of S. mitis biovar 1 and S. oralis may play an important role in caries development by modifying the environment in dental plaque to become favourable for the succession of aciduric species. The study furthermore emphasises the need for detailed species and biovar identification of oral streptococci and for recognition of the significant physiological differences that occur within single species.
Modulation of α-Actin and α-Actinin Proteins in Cardiomyocytes by Retinoic Acid during Development
Authors: Aránega A.E. , Velez C. , Prados J. , Melguizo C. , Marchal J.A. , Arena N. , Alvarez L. , Aránega A.
Published: April 2003

Early heart development is known to be sensitive to retinoid concentrations. Although the influence of retinoids on cardiac morphogenesis has been described previously, the effect of retinoids on cardiomyocyte differentiation during development has not been characterized. We quantified the effects of the retinoic acids all-trans RA and 13-cis RA on α-actin and α-actinin at the subcellular level in cultures of chick embryo cardiomyocytes obtained from Hamburger and Hamilton’s (HH) stage 22, 32 and 40 embryos. The retinoids increased the concentration of α-actin and α-actinin in the cytoplasmic and cytoskeletal fractions of cells at all three stages of development. The effect was greatest in cardiomyocytes treated for 24 h with all-trans RA and in cells from HH22 embryos. The greatest increases in α-actin concentration occurred in the cytoskeletal fraction of HH22 cells cultured for 24 h with all-trans or 13-cis RA, whereas the greatest increases in α-actinin were found in the cytoplasmic fraction of HH22 cells exposed to retinoids for 24 h. We conclude that retinoic acid plays a role in the reorganization of the pattern of sarcomeric protein expression during cardiomyocyte differentiation.