bluuebunny/crossref_metadata_2025 huggingface dataset:
Recovery of Motor Functions following Hemiparetic Stroke: A Clinical and Magnetic Resonance-Morphometric Study
Authors: Binkofski F. , Seitz R.J. , Hackländer T. , Pawelec D. , Mau J. , Freund H.-J.
Published: April 2003

Predictors for the degree of clinical recovery after stroke are still poorly defined. In this study we tried to assess the predictive value of clinical data and of lesion size for motor recovery after ischemic stroke. In 52 hemiparetic patients we monitored the course of clinical recovery by a dedicated score of sensorimotor hand function after their first stroke. The course of the lesion size was measured in proton density magnetic resonance images. Three groups of patients were identified. Patients with moderate initial motor deficit recovered almost completely within 9 days (17/17, group 1). From the patients with severe initial motor deficit, about equal numbers recovered (16/35, group 2) or remained severely impaired during the entire observation period of more than 6 months (19/35, group 3). There was no correlation between changes of lesion size and motor deficit. Logistic regression of probability of good clinical outcome on initial lesion size, initial motor score and subcortical versus cortical location of lesion showed that only the initial motor score was predictive (p = 0.006). A relative improvement of the initial motor score of about 20% in the first 4 weeks after stroke appeared to be a relevant cut point for good outcome. The data indicate that patients with mild initial motor deficits recover well, whereas severely affected patients may differ in outcome. Since lesion size was not correlated with outcome the amount of spared residual function appeared as major determinant for the capacity for motor recovery.
MR Angiographic Evaluation of Carotid and Intracranial Arteries in Japanese Patients Scheduled for Coronary Artery Bypass Grafting
Authors: Uehara Toshiyuki , Tabuchi Masayasu , Kozawa Shu-ichi , Mori Etsuro
Published: April 2003

Background and Purpose: Stroke is a serious complication of coronary artery bypass grafting (CABG). Preoperative evaluation of the cerebral arteries to identify patients at increased risk of stroke after CABG is important. In a prospective study, we evaluated cerebral artery occlusive lesions with MR angiography in Japanese patients scheduled to undergo CABG to determine the prevalence of occlusive diseases in the extracranial carotid and intracranial arteries in this population and to identify preoperative risk factors for these patients. Methods: The subjects were 151 consecutive patients (115 men and 36 women ranging in age from 41 to 82 years) who were scheduled for CABG under nonemergency conditions between October 1995 and February 1998. Carotid and intracranial arteries were examined for occlusive lesions with MR angiography. Patient demographics and risk factors including age, sex, hypertension, diabetes mellitus, hyperlipidemia, smoking habit, history of stroke, peripheral vascular disease and preoperative thromboembolic infarcts revealed by MR imaging were recorded and analyzed. Results: Cervical carotid artery stenoses of more than 50% narrowing were detected in 16.6% of the subjects, and intracranial artery stenoses of more than 50% narrowing were detected in 21.2% of the subjects. Multiple logistic regression analyses identified peripheral vascular disease and lacunar infarcts in the basal ganglia as significant and independent predictors of cervical carotid arterial stenoses. No significant predictor for intracranial arterial stenoses was identified. Conclusions: The prevalence of extracranial carotid and intracranial artery stenosis in Japanese patients scheduled for CABG is considerably high. MR angiography is of value of identifying these patients. Preoperative evaluation of cranial arteries is recommended, particularly in patients with peripheral vascular disease and infarcts in the basal ganglia.
Poststroke Depression in Acute Phase after Stroke
Authors: Berg Anu , Palomäki Heikki , Lehtihalmes Matti , Lönnqvist Jouko , Kaste Markku
Published: April 2003

We studied factors associated with acute poststroke depression in 100 patients, aged 27–70, 2 weeks after their first clinically significant stroke. Depressive symptoms were relatively common (27% Beck Depression Inventory ≧10), but the prevalence of major depression was only 5.6%. Older patients were most vulnerable to poststroke depression. Patients with left hemisphere lesion had no more depression than other patients, but when the lesion was in the left hemisphere or in the brainstem, stroke severity was associated with depression.
Characterization of Cerebral Small Vessel Disease by Proton Spectroscopy and Morphological Magnetic Resonance
Authors: Hund-Georgiadis Margret , Norris David G. , Guthke Thomas , von Cramon D. Yves
Published: April 2003

This study sought to investigate whether clinical and neuropsychological impairment in cerebral small vessel disease (CSVD) can be evaluated by proton spectroscopy (1H-MRS) and structural magnetic resonance (MR) imaging. Sixteen patients with CSVD and 15 healthy age-matched controls participated in the study. In addition to spectroscopic and structural MR examination all patients underwent a comprehensive clinical and neuropsychological investigation. Significant differences in between patients and controls were revealed by 1H-MRS in the parietal white matter: decreased metabolic ratios of N-acetyl aspartate to choline (NAA/Cho; patients: 1.37 ± 0.17, control: 1.72 ± 0.25, p < 0.001) and of N-acetyl aspartate to creatin (NAA/Cr; patients: 1.41 ± 0.15, control: 1.66 ± 0.2, p < 0.01) indicated a pathological state. Evaluation of spectroscopic and neuropsychological data revealed a close relation between attentional impairment, i.e. delayed cerebral transmission time and decreased NAA/Cho and NAA/Cr (r = 0.62, p = 0.014). In sum, 1H-MRS allowed a clear discrimination between patients with CSVD and age-matched normal controls. Moreover, comparisons of 1H-MRS and neuropsychological data suggested that NAA metabolic levels, and particularly the delay in cerebral transmission time, could be potential predictors of the severeness of attentional impairment.
Long-Term Follow-Up of Patients after Intraarterial Thrombolytic Therapy of Acute Vertebrobasilar Artery Occlusion
Authors: Sliwka Ulrich , Mull Michael , Stelzer Angelika , Diehl Rolf , Noth Johannes
Published: April 2003

Local thrombolysis may reduce mortality after acute vertebrobasilar artery occlusion. We focused on variables affecting recanalization, outcome and long-term prognosis. Thirty-six patients with vertebrobasilar artery occlusion were treated with local intraarterial thrombolytic therapy. Four of the survivors were among the 16 patients without recanalization. Recanalization was associated with a higher survival rate. Top-of-the-basilar-type occlusions have the highest recanalization rate. The thrombolytic medication used did not influence the recanalization frequency. One patient died due to an intracerebral bleed after thrombolysis. There was no association between the time interval (greater or less than 6 h) between the onset of symptoms and therapy initiation and survival. Relapses during follow-up (mean follow-up 3.7 years) did not occur. MRI/MRA and ultrasound studies during follow-up showed unchanged results in these patients. All survivors at the time of follow-up lived at home.
Altered Food Preference after Cortical Infarction: Korean Style
Authors: Kim Jong S. , Choi Smi
Published: April 2003

Background: Altered food preference or preoccupation with certain food after stroke has been rarely described in the literature. Methods: We report four Korean patients who developed altered food preference secondary to unilateral cortical infarction. Results: Two patients showed preoccupation with meat such as Pulgogi or Kalbi (roast beef flavored with ingredients), which had not been their preference prior to the occurrence of stroke. All the patients became intolerant to the smell and taste of mackerel, and two disfavored hot Kimchi (cabbage salted with hot pepper). Quantitative taste assessment done in the patients revealed decreased taste perception in a variable pattern along with dysgeusia. Imaging studies showed that the region commonly involved was the frontal opercular area corresponding to the taste cortex. Conclusion: It is suggested that strokes involving the taste cortex may produce altered food preference associated with decreased taste sensation.
Development of Human Fetal Pancreas after Transplantation into SCID Mice
Authors: Si Zhaoyi , Tuch Bernard E. , Walsh David A.
Published: April 2003

Only a small component of human fetal pancreas consists of β cells, and yet this tissue is capable of normalizing the blood glucose levels of diabetic recipients when transplanted. The time taken to achieve this goal is several months, during which time the tissue proliferates and eventually differentiates into β cells. The dynamics of β cell development have not been described previously. We transplanted human fetal pancreas beneath the renal capsule of immunodeficient mice and analysed the grafts for a period of 12 weeks using antibodies against exocrine cells (lipase), endocrine cells and protodifferentiated duct cells. Exocrine cells constituted 48% of all epithelial cells in the untransplanted pancreas, with duct cells comprising 29% and endocrine cells 16% (β cells 7%). The percentage of exocrine cells declined with time after transplantation, with only a small number undergoing apoptosis, and the duct cells increased, the values for these two cell types at 12 weeks being 20 and 57%, respectively. Both cell types appeared to proliferate equally for up to 8 weeks after transplantation, but only duct cells thereafter. Endocrine cells began to increase from 8 weeks after transplantation, representing 28% of epithelial cells (β cells 11%) at this time. Intermediate cells, that is, cells expressing the characteristics of more than one type of mature pancreatic cell, were observed both in the ungrafted pancreas and after transplantation. The commonest intermediate cell type was duct/exocrine, with exocrine/endocrine and duct/endocrine cells also observed, suggesting active transdifferentiation from one cell type to another. We hypothesize that following the transplantation of human fetal pancreatic tissue, exocrine cells mostly transdifferentiate into duct cells and these eventually develop into endocrine cells, in particular β cells.
Interleukin-6 Signaling and Embryonic Mouse Submandibular Salivary Gland Morphogenesis
Authors: Melnick Michael , Chen Haiming , Zhou Yan-Min , Jaskoll Tina
Published: April 2003

Interleukin-6 (IL-6) is a multifunctional cytokine that mediates cell growth, differentiation, and survival. It was the objective of the present study to investigate the possible function(s) of IL-6 signaling in embryonic mouse submandibular salivary gland (SMG) morphogenesis. After characterizing in vivo mRNA and protein expression of various constituents of this pathway, we utilized in vitro strategies to investigate the phenotypic outcomes of enhanced IL-6-induced signaling and immunoperturbation of IL-6 binding to cognate receptors. These experiments demonstrate: (1) there is a significant increase of IL-6 mRNA with progressive SMG development, and that this is highly correlated with TNF transcript levels; (2) IL-6 and its cognate receptors are immunolocalized in SMG branching epithelia from the canalicular stage to the late terminal bud stage, as are other constituents of the IL-6 pathway; (3) as compared to controls, IL-6-supplemented explants exhibit a substantial increase in overall size and in the number of ductal branches and terminal buds, as well as a highly significant increase in epithelial cell proliferation; (4) SMG explants cultured in the presence of anti-IL-6 neutralizing antibodies exhibit a marked decrease in epithelial ducts and terminal buds, concomitant with a significant decline in cell proliferation and a highly significant increase in apoptosis. Taken together, our experimental results indicate that IL-6 signaling is important to SMG developmental homeostasis.
Granulated Decidual Cells in the Mouse Deciduoma: A Putative Source of Decidual Prolactin in Mice
Authors: Monice Fernanda L. , Andrade Célia G.T. , Abrahamsohn Paulo A. , Soto-Suazo Maurício , Oliveira Sérgio F. , Zorn Telma M.T.
Published: April 2003

Decidual cells are endometrial fibroblasts that redifferentiate during pregnancy in several species of mammals. In this work, we describe a subpopulation of resident decidual cells in the mouse endometrium that are joined by intercellular junctions and have cytoplasmic granules. Decidualization was induced in pseudopregnant mice on the 4th day of pseudopregnancy by injection of 30 µl of arachis oil into the uterine lumen. The uteri were collected on day 8 of pseudopregnancy (at 4 p.m., 8 p.m. and 11 p.m.) and on day 9 (at 8 a.m.). The tissues were fixed for light and electron microscopy. During day 8 of pseudopregnancy, granulated cells were present at the antimesometrial pole of the endometrium; they were concentrated at the periphery of the antimesometrial decidua and disappeared on day 9 of pseudopregnancy. The cytoplasm of the granulated decidual cells had acidophilic granules that stained also with periodic acid-Schiff (PAS). These granules stained with anti-rat prolactin antibody in both light and electron microscope immunocytochemical preparations. Vacuoles of various sizes were always present in the granulated cells. A PAS-positive and prolactin-stained material was often deposited at the periphery of the vacuoles. Our results indicate that the granulated decidual cells are the source of decidual prolactin which accumulates in cytoplasmic granules. These granulated cells therefore form a transient gland in the mouse antimesometrial endometrium (granulated decidual gland).
Light and Ultrastructural Immunocytochemical Study of Prolactin Cells in Ovine Adenohypophysis
Authors: Bernabé A. , Gómez M.A. , Seva J. , Serrano J. , Sánchez J. , Navarro J.A.
Published: April 2003

The influence of lactation and weaning on the number, distribution, and structure of mammotroph cells (PRL cells) in ewes was studied using immunocytochemical procedures for light and electron microscopy, as well as morphometric and stereological techniques. The adenohypophyseal gland of 12 ewes of the Segureña breed at different stages of milk production and weaning were analysed, while the same organ of 3 ewes in anestrus served as control. During lactation, PRL cells increased in number and decreased in size. Ultrastructurally, these cells showed a well-developed rough endoplasmic reticulum (RER) and Golgi complex (GC), and large secretory granules. These findings point to increased synthesis and secretion activities during lactation, and a decrease after weaning. One day after weaning ‘storage’ cells increased in number, and crinophagy became evident 7 days after weaning, when the first ‘inactive’ cells were seen (10% of total cells). In anestrus these last cells represented 40% of the total, and showed scarce granules, signs of inactivity, lysosomes and lipid droplets.
Brief Exposure to Testosterone Is Sufficient to Induce Sex Differences in the Rabbit Masseter Muscle
Authors: Reader Michael , Schwartz Gail , English Arthur W.
Published: April 2003

In order to evaluate whether testosterone is responsible for inducing long-lasting sex differences in myosin heavy chain gene expression in the rabbit masseter muscle, we castrated young adult animals and administered supra-physiologic doses of testosterone for 3 or 6 weeks duration. Biopsies were taken from the masseter muscles of these animals at the time of castration and 3, 6 and 9 weeks later. Both immunoblot and immunohistochemical analyses of the myosin heavy chain (MyHC) isoform content of these muscle samples were performed. Exposure to testosterone for either duration resulted in a dramatic decrease in the content of the cardiac alpha MyHC isoform and a comparable increase in the content of the IIa MyHC isoform. The decrease in the cardiac alpha MyHC isoform content persisted for as long as 6 weeks after the end of treatment, but the increase in the content of the IIa MyHC isoform declined to normal during this time. Significant numbers of fibers were found containing both the cardiac alpha (and slow) and the IIa isoforms. Several fibers were encountered that contained both IIa and, presumably, the IIx isoform. Thus, a brief exposure to testosterone during postnatal maturation is able to produce a long lasting myosin heavy chain isoform switch that is similar in magnitude to that found during normal development.
Orofacial Deep and Cutaneous Tissue Inflammation and Trigeminal Neuronal Activation
Authors: Imbe Hiroki , Iwata Koichi , Zhou Qi-Qi , Zou Shiping , Dubner Ronald , Ren Ke
Published: April 2003

A rat model has been developed to characterize the responses of brainstem trigeminal neurons to orofacial deep and cutaneous tissue inflammation and hyperalgesia. Complete Freund’s adjuvant (CFA) was injected unilaterally into the rat temporomandibular joint (TMJ) or perioral (PO) skin to produce inflammation in deep or cutaneous tissues, respectively. The TMJ and PO inflammation resulted in orofacial behavioral hyperalgesia and allodynia that peaked within 4–24 h and persisted for at least 2 weeks. Compared to cutaneous CFA injection, the injection of CFA into the TMJ produced a significantly stronger inflammation associated with a selective upregulation of preprodynorphin mRNA in the trigeminal spinal complex, an enhanced medullary dorsal horn hyperexcitability, and a greater trigeminal Fos protein expression, a marker of neuronal activation. The Fos-LI induced by TMJ inflammation persisted longer, was more intense, particularly in the superficial laminae, and more widespread rostrocaudally. Thus, the inflammatory irritant produces a stronger effect in deep than in cutaneous orofacial tissue. As there is heavy innervation of the TMJ by unmyelinated nerve endings, a strong nociceptive primary afferent barrage is expected following inflammation. An increase in TMJ C-fiber input after inflammation and strong central neuronal activation may initiate central hyperexcitability and contribute to persistent pain associated with temporomandibular disorders. Since deep inputs may be more effective in inducing central neuronal excitation than cutaneous inputs, greater sensory disturbances may occur in pain conditions involving deep tissues than in those involving cutaneous tissues.
Inflammation and Bony Changes at the Temporomandibular Joint
Authors: Kacena Melissa A. , Merrel Greg A. , Konda Sanjit R. , Wilson Kimberly M. , Xi Yougen , Horowitz Mark C.
Published: April 2003

Cytokines help mediate the acute and chronic inflammation and associated destruction of connective tissue in arthritic temporomandibular joints (TMJ). The proinflammatory cytokines TNFα, IL-1β, IL-6, IL-8, and IFN-γ are associated with inflammation in synovial joints and connective tissue destruction. Therefore, the increased levels of these cytokines in the synovial fluid of temporomandibular disorder (TMD) patients would be expected. Conversely, IL-1ra and IL-10 acts as inhibitors to these proinflammatory cytokines. Thus, in TMD patients, low levels of IL-1ra and IL-10 might be expected. A review of studies from multiple investigators confirms that proinflammatory cytokine levels increase in TMD patients, IL-1ra levels are also increased, and IL-10 levels remain unchanged. Because IL-10 can inhibit TNFα, IL-1, IL-6, and IL-8, the lack of IL-10 in the TMJ in the face of the other studies showing increases in TNFα, IL-1β, IL-6, and IL-8 could partially explain the exacerbation of the associated osteoarthritis. In addition, although IL-1ra levels are elevated in most of the TMD patients, the increases do not appear to be sufficient to inhibit the inflammation and connective tissue degradation associated with IL-1β. Thus, it appears that treatment of TMD requires a delicate balance between proinflammatory cytokines and cytokine inhibitors such as IL-1ra and IL-10.
Bone Blood Flow and Vascular Reactivity
Authors: Fleming John T. , Barati Michelle T. , Beck Dennis J. , Dodds James C. , Malkani Arthur L. , Parameswaran Dushi , Soukhova Galia K. , Voor Michael J. , Feitelson Jeremy B.A.
Published: April 2003

Blood flow is essential for normal bone growth and bone repair. Like other organs, the regulation of blood flow to bone is complex and involves numerous physiologic mechanisms including the sympathetic nervous system, circulating hormones, and local metabolic factors. Our studies addressed the following questions: (1) Which endogenous vasoconstrictor agents regulate in vivo blood flow to bone? (2) Does a decrease in bone vascular reactivity to vasoconstrictor hormones account for the increase in blood flow during bone healing? (3) Does the endothelium influence bone arteriolar function? An intact bone model was developed in the rat to assess hormonal regulation of in vivo bone blood flow and in vivo bone vascular reactivity. An isolated, perfused bone arteriole preparation was employed to characterize the responsiveness of small resistance-size arterioles (diameter < 100 µm) to vasoconstrictor hormones and to evaluate the role of the vascular endothelium to modulate vascular smooth muscle reactivity. Our results indicate that: (1) though exogenous endothelin is a potent constrictor of the in vivo bone vasculature, endogenous endothelin does not actively regulate in vivo blood flow; (2) the increase in blood flow to a bone injury site is not due to a decrease in bone vascular sensitivity to norepinephrine, and (3) isolated bone arterioles of young rats are very sensitive to vasoconstrictor hormones but exhibit only modest endothelium-mediated vasodilation.
Immunofluorescence and Electron-Microscopic Observations of Intermediate Cells in the Pancreas of Mice, Rats and Humans
Authors: Aughsteen Adib A.
Published: April 2003

The immunohistochemical method supplemented with a transmission electron-microscopic survey was used to investigate the pancreas of mice, rats and humans to demonstrate intermediate cells. Indirect immunofluorescence was applied to paraffin sections of pancreatic samples of normal rats and autopsied humans to localize amylase in the islets and excretory duct cells. The amylase immunofluorescent spots were occasionally detected in the apices and perinuclear cytoplasm of few islet and excretory duct cells, which completely disappeared in the specificity control sections. These cells, respectively, represented the islet amylase and duct amylase intermediate cells. The ultrastructural survey was conducted on pancreatic tissue samples from normal and streptozotocin-diabetic mice and rats to prove the existence of these intermediate cells. Three morphologically distinct types of intermediate cells were recognized and characterized into β-acinar, α-acinar and duct acinar types. The β-acinar and α-acinar cells contained numerous secretory granules with few large and dense, membrane-bound zymogen granules. No clear difference in the frequency of these cells between normal and diabetic tissues was qualitatively observed in either mice or rats. The duct acinar cells were occasionally seen in few small intercalated ducts of the normal mouse pancreas, which contained few dense, membrane-bound zymogen granules adjacent to a prominent Golgi complex. On the other hand, no δ-acinar, pancreatic polypeptide (PP)-acinar or acinoislet cells were observed in both normal and diabetic animals. In conclusion, the present study provides immunohistochemical and morphological evidence on the existence of different types of intermediate cells in the normal and streptozotocin-diabetic pancreas of mice, rats and humans. Although no prevalence of these cells in the streptozotocin-diabetic pancreas was observed qualitatively, their existence throws light on the possible transformation between structurally and functionally different pancreatic cells when subjected to pathological trauma. This concept might be of great significance in β-cell regeneration in insulin-dependent diabetes mellitus.
Comparative Evaluation of Nuclear Morphology of Equine Oocytes Aspirated in vivo and Stained with Hoechst and Orcein
Authors: Bézard Jacqueline , Bøgh Ingrid B. , Duchamp Guy , Hyttel Poul , Greve Torben
Published: April 2003

Nuclear maturation of equine oocytes was assessed immediately after in vivo collection. A double-staining technique (Hoechst and orcein) was used on the same oocytes to visualize nuclear morphology, i.e. to evaluate the chromatin configurations of each oocyte after Hoechst in relation to the nuclear morphology after orcein staining. The proportion of oocytes evaluated as germinal vesicle stages was significantly (p < 0.02) lower after Hoechst (14.5%) than after orcein staining (29.0%), while the incidence of the so-called dense chromatin stage was assessed to be higher (p < 0.05) after Hoechst than after orcein staining (14.5 vs. 6.5%). There was no difference between Hoechst and orcein staining in the incidence of diakinesis and germinal vesicle breakdown stages, respectively (44.9 vs. 42.0%), and the same applied for metaphase I (11.6 vs. 8.0%), metaphase II (7.2 vs. 8.0%) and degenerated stages (7.2 vs. 6.5%). It was concluded that the interpretation of the meiotic stages may differ between Hoechst and orcein staining and in a large proportion of equine oocytes the nuclear border may not be visualized on orcein staining.
Psychotic Symptoms and Emotional Distress in Patients with Guillain-Barré Syndrome
Authors: Weiss H. , Rastan V. , Müllges W. , Wagner R.F. , Toyka K.V.
Published: April 2003

Psychological disturbances in 49 most severely compromised Guillain-Barré syndrome patients were prospectively studied by a semistructured interview and assessed by repeat psychiatric examination during the patients’ stay in the neuro-intensive care unit (ICU). Additional information was obtained from attending physicians, nurses and relatives. Anxiety (82%), acute stress disorder, depressive episodes (67%) and brief reactive psychosis (25%) were observed, with oneiroid psychosis (14%) among the latter. Psychotic episodes were strongly associated (p < 0.001) with severe tetraparesis, artificial ventilation and multiple cranial nerve dysfunction. CSF protein concentration was also correlated with the occurrence of psychotic symptoms. Patients themselves experienced loss of communication to be the most difficult condition to cope with. Fifty-five percent explicitly felt reassured by the environment of the ICU and 90% described contact with relatives to be most helpful. Our data suggest that motor deprivation and loss of communication are the conditions most closely connected with the occurrence of psychotic symptoms. Therapeutically, continuous psychosocial support and psychopharmacological measures may both be valuable tools to ameliorate distress.
Efficacy, Tolerability and Safety of Oral Eletriptan and Ergotamine plus Caffeine (Cafergot®) in the Acute Treatment of Migraine: A Multicentre, Randomised, Double-Blind, Placebo-Controlled Comparison
Authors: Diener Hans-Christoph , Jansen Jan-Peter , Reches Avinoan , Pascual Julio , Pitei Daniela , Steiner Timothy J.
Published: April 2003

The 5-HT1B/1D/1F agonist eletriptan, at an oral dose of 80 mg, has been shown to be more efficacious than sumatriptan 100 mg and placebo in the treatment of migraine attacks with or without aura. Another commonly prescribed oral treatment for migraine attacks is Cafergot® (1 mg ergotamine tartrate with 100 mg caffeine per tablet). The efficacy, tolerability and safety of 40- and 80-mg doses of eletriptan and 2 tablets of Cafergot® were compared in a double-blind, randomised, placebo-controlled, parallel-group trial involving 733 migraine patients. Patients recorded symptoms at baseline (before treatment) and 1, 2, 4 and 24 h after dosing. Headache intensity was assessed on a 4-point scale (3 = severe pain, 2 = moderate pain, 1 = mild pain, 0 = no pain). Significantly more eletriptan-treated patients (80 mg, 68%; 40 mg, 54%) than Cafergot-treated patients (33%; p < 0.001) reported headache response (improvement from moderate-to-severe to mild or no pain) at 2 h. Substantially more eletriptan recipients reported no pain (80 mg, 38%; 40 mg, 28%; Cafergot, 10%; placebo, 5%; p < 0.001). Eletriptan headache response rates at 1 h were significantly higher (80 mg, 39%; 40 mg, 29%; Cafergot, 13%; placebo, 13%; p < 0.002 for each comparison). Both doses of eletriptan were significantly more effective than Cafergot in reducing nausea (p < 0.0001), photophobia (80 mg, p < 0.0001; 40 mg, p < 0.002), phonophobia (80 mg, p < 0.0001; 40 mg, p < 0.003) and functional impairment (p ≤ 0.001) at 2 h. Adverse events were generally mild or moderate and transient. This randomised trial shows that oral eletriptan is more efficacious in the acute treatment of migraine than oral Cafergot and is well tolerated.
Downregulation of Striatal Dopamine D2 Receptors in Advanced Parkinson’s Disease Contributes to the Development of Motor Fluctuation
Authors: Hwang Wen-Juh , Yao Wei-Jen , Wey Shiaw-Pyng , Shen Lie-Hang , Ting Gann
Published: April 2003

The purpose of this study was to evaluate the contribution of the postsynaptic mechanism to the development of motor fluctuation in advanced Parkinson’s disease (PD). We used 123I-iodobenzamide single-photon emission computed tomography to measure the striatal dopamine D2 receptor densities in early levodopa-naïve PD, chronic PD with stable levodopa response, and advanced PD with fluctuating levodopa response. The basal ganglia/frontal cortex ratios at both hemispheres were calculated and averaged. PD patients with fluctuating levodopa response showed a significant decrease in striatal dopamine D2 receptor densities compared to those with early (1.57 ± 0.20 vs. 1.77 ± 0.12, p = 0.009) or chronic stable PD (1.57 ± 0.20 vs. 1.77 ± 0.10, p = 0.024). We conclude that the decreased D2 receptor densities in advanced PD reduced the ‘safety factor’ for synaptic transmission and contributed to the development of motor fluctuation.
Is the Right Amygdala Involved in Visuospatial Memory? Evidence from MRI Volumetric Measures
Authors: Pegna Alan J. , Caldara-Schnetzer Anne-Sarah , Perrig Stephen H. , Lazeyras François , Khateb Asaid , Landis Theodor , Seeck Margitta
Published: April 2003

Quantitative MRI measurement of hippocampal sclerosis in patients suffering from temporal lobe epilepsy (TLE) have, as yet, failed to evidence any correlation between the right hippocampus and visuospatial memory. In this report, word learning and design learning tasks were carried out as well as MRI volumetric measurements of the hippocampus and amygdala in order to verify possible modality-specific correlations between function and structure. Delayed recall indices in our memory tasks provided significant results. Visuoverbal ratios differed between right and left TLE groups, as did laterality indices of hippocampal and amygdalar volumes. Furthermore, correlations were found between the left hippocampal volume and verbal memory, and between the right amygdala and visuospatial memory. We suggest that the difficulty encountered in establishing a correlation between right temporal structures and visuospatial memory could come both from the type of test employed and the structures considered.
Comparative Study of a Portable Prothrombin Time Monitor Employing Three Different Systems in Oral Anticoagulant Units
Authors: Vacas M. , Fernández M.A. , Martínez-Brotons F. , Lafuente P.J. , Ripoll F. , Alvarez C. , Iriarte J.A.
Published: April 2003

The aim of this study was to evaluate the accuracy of the portable coagulometer CoaguChek® (Roche Diagnostics) as a prothrombin time (PT) monitor, and to correlate capillary blood results with those of three different routine methods used for monitoring oral anticoagulant therapy (OAT): capillary, plasma and whole blood samples. Three hospitals participated in the study with a total of 235 patients on OAT. The international normalized ratio (INR) results obtained with CoaguChek were compared with those obtained using each of the routine methods. The study presents a good correlation between the PT monitor and the three methods studied: r = 0.9745 (hospital A), r = 0.9283 (hospital B), r = 0.9136 (hospital C). A simplified concordance test of the methods results in a nine-field comparison table showing concordances of 87.2, 85.7 and 68.4%, respectively. The absolute difference (mean ± SD) between laboratory A and CoaguChek INRs was 0.0571 ± 0.2042, with values of 0.04286 ± 0.3906 for laboratory B and 0.6986 ± 0.6170 for laboratory C. These results confirm that CoaguChek could be used as a new method for oral anticoagulant monitoring, and is in best agreement with the capillary blood PT system.
Measurement of a Newly Developed Thrombomodulin Addition Activated Partial Thromboplastin Time Assay in Patients with Deep Venous Thrombosis
Authors: Suehisa Etsuji , Toku Masayuki , Kawasaki Tomio , Kanakura Yuzuru
Published: April 2003

We developed a simple assay using rabbit thrombomodulin (TM) based on an activated partial thromboplastin time method, which detected the response to TM in plasma coagulation. We call it thrombomodulin addition clotting time (TACT). The anticoagulant response to TM was calculated by dividing the clotting time with TM by the clotting time with buffer solution. Results were expressed as TACT ratio, which indicates the degree of inhibition of plasma clotting by TM. Using this assay, we measured the TACT ratio in 80 patients with deep-vein thrombosis (DVT) and in 126 controls matched to the patients according to age and sex. A significant difference in the TACT ratio was observed between patients with DVT (mean 1.874) and controls (mean 1.956) (p < 0.001). Twenty- three patients (29%) had TACT ratios below the 10th percentile (1.757) of distribution of control subjects (odds ratio: 3.5; 95% confidence interval (CI): 1.7–7.2). After excluding subjects with a deficiency of protein C, protein S and antithrombin III, we found an odds ratio for DVT of 3.4 (95% CI: 1.6–7.2). These data suggest that natural anticoagulant deficiencies do not influence the TACT ratio, and our case-control study may show that the plasma of patients with DVT has a low response to TM.
Enhanced Thrombolysis Induced by Argatroban or Activated Protein C in the Presence or Absence of Staphylokinase, Measured in an in vivo Animal Model Using Mesenteric Arterioles
Authors: Hashimoto Masaru , Watanabe Sadahiro , Oiwa Kazuhiro , Ohta Yoshio , Kishi Takeo , Okamoto Tadashi , Giddings John C. , Yamamoto Junichiro
Published: April 2003

Successful administration of thrombolytic agents is associated with vessel reocclusion in a high proportion of cases. We have previously established an animal model to investigate platelet-rich thrombolytic mechanisms in vivo and demonstrated that recombinant staphylokinase (rSAK)-induced thrombolysis was enhanced by the concomitant administration of the direct thrombin inhibitor argatroban. The present study expanded the use of this model by comparing arterial and venous thrombolysis using advanced image analysis software. Mural thrombi were formed by Helium-Neon laser irradiation in mesenteric arterioles and were shown to be lysed, dose-dependently, by smaller amounts of rSAK than those required in venules. Activated protein C (APC), as well as argatroban, enhanced the rSAK-induced thrombolysis. APC or argatroban also induced thrombolysis in the absence of rSAK, and the effect was inhibited by tranexamic acid. The enhanced thrombolysis induced by APC or argatroban in the presence or absence of rSAK may be due to increased endogenous thrombolysis mediated by the inhibition of thrombin activity or delayed thrombin generation.
The Use of Snake Venom Toxins as Tools to Study Platelet Receptors for Collagen and von Willebrand Factor
Authors: Andrews Robert K. , Kamiguti Aura S. , Berlanga Oscar , Leduc Mireille , Theakston R. David G. , Watson Steve P.
Published: April 2003

A large proportion of the biologically active proteins and peptides present within snake venoms interact with components of the haemostatic system to promote or inhibit the normal sequence of events that lead to clot formation. The venom proteins achieve their effects through interaction with various components of the coagulation cascade, endothelial matrix and platelets. Within the latter group, a number of venom proteins target the interaction of platelets with the major adhesive proteins, von Willebrand factor and collagen. The venom proteins bind either the adhesive protein itself or their receptors on the platelet surface, notably GP-Ib-IX-V and GPVI. This review discusses the substantial contribution that venom proteins have made to our understanding of the role of these two adhesive proteins and their receptors (excluding GPIIb-IIIa) in platelet regulation.
New Insights on Disintegrin-Receptor Interactions: Eristostatin and Melanoma Cells
Authors: McLane M.A. , Kuchar M.A. , Brando C. , Santoli D. , Paquette-Straub C.A. , Miele M.E.
Published: April 2003

Viper venom disintegrins have been used frequently to study the cellular receptors which characterize various types of cells, including platelets, endothelial cells and cancer cells. While the majority of such analyses have pointed to involvement of integrin receptors αvβ3, α5β1 or αIIbβ3, this may not always be so. Eristostatin, from Eristocophis macmahoni, is a potent inhibitor of ADP-induced platelet aggregation as well as of human and murine melanoma metastases in mouse model systems. This disintegrin requires an RGDW motif, as well as an intact C-terminus, in order to interact with both platelets and four different types of melanoma cells. Eristostatin causes nonmetastatic SBc12 melanoma cells to show higher susceptibility to specific killing by NK-like TALL-104 cells. While it is known that eristostatin binds to αIIbβ3 on platelets, the receptor with which eristostatin binds to the melanoma cells has not yet been identified.
Snake Venom Prothrombin Activators Homologous to Blood Coagulation Factor Xa
Authors: Joseph Jeremiah S. , Kini R. Manjunatha
Published: April 2003

We have recently determined the complete amino acid sequence of trocarin, a group D prothrombin activator from the venom of Tropidechis carinatus (Australian rough-scaled snake). This proteinase is both functionally and structurally similar to mammalian blood coagulation factor Xa. It shows ∼70% homology and possesses the characteristic Gla domain, two EGF domains and serine proteinase domain. To examine structure-function relationships, we generated a molecular model of trocarin based on a human factor Xa des-Gla crystal structure (1xka) as template. Based on known sites of interaction between mammalian factor Xa, factor Va and prothrombin, structure-function relationships of trocarin were explored. Unlike factor Xa, trocarin is glycosylated and has a large carbohydrate moiety at the entrance to its active site pocket. This might contribute to differences observed in the kinetics of hydrolysis of synthetic substrates by trocarin as compared to human factor Xa. A Ca2+-binding loop present in the heavy chain of factor Xa also seems to be lost in trocarin. In addition to its role in hemostasis, factor Xa shows other biological effects, including inflammation via its interaction with effector protease receptor-1 (EPR-1). Interestingly, the EPR-1 recognition site is distinctly different in trocarin, the functional consequences of which are being investigated.
Factor V Activation and Inactivation by Venom Proteases
Authors: Rosing Jan , Govers-Riemslag José W.P. , Yukelson Lev , Tans Guido
Published: April 2003

Blood coagulation factor V is a single-chain glycoprotein with Mr = 330,000 which plays an important role in the procoagulant and anticoagulant pathways. Thrombin activates factor V into factor Va, a two-chain molecule which is composed of a heavy (Mr = 105,000) and a light chain (Mr = 71,000/74,000). Factor Va accelerates factor Xa-catalysed prothrombin activation more than 1,000-fold and under physiological conditions the cofactor activity of factor Va in prothrombin activation is down-regulated by activated protein C. Factor V can also be activated by a wide variety of snake venoms (e.g. from Vipera species, Naja naja oxiana, Bothrops atrox) and by proteases present in the bristles of a South American caterpillar (Lonomia achelous). Some venoms, notably of Vipera lebetina turanica and Lonomia achelous, contain proteases that are able to inactivate factor V or factor Va. Venom factor V activators are excellent tools in studying the structure-function relationship of factor V(a) and they are also used in diagnostic tests for quantification of plasma factor V levels and for the screening of defects in the protein C pathway. In this review, the structural and functional properties of animal venom factor V activators and inactivators is described.
Anticoagulant Venom and Mammalian Secreted Phospholipases A2: Protein- versus Phospholipid-Dependent Mechanism of Action
Authors: Mounier Carine M. , Bon Cassian , Kini R. Manjunatha
Published: April 2003

Some venom and mammalian-secreted phospholipases A2 (sPLA2) have been described to exert an anticoagulant effect. This review will discuss and compare phospholipid-dependent versus protein-dependent mechanisms of action of these sPLA2 on the coagulation cascade. The importance of venom proteins, and of the study of their pharmacological effects, to explore the physiological functions of homologous mammalian proteins is also pointed out.
Touch: Its Communicative Functions in Infancy
Authors: Hertenstein Matthew J.
Published: April 2003

The communicative functions that the tactile modality serves in infancy have been severely neglected by researchers. The present article highlights the importance of touch by addressing two questions. First, what is communicated to infants by touch from their caregivers? In addition to the common notion that touch regulates arousal levels, it is argued that touch is capable of communicating valenced and discrete emotions as well as specific information. Second, how does meaning come about from the touch that adults administer to infants? This question is addressed by discussing specific qualities and parameters of touch and three mechanisms by which infants gain meaning from touch. Empirical evidence is provided and hypotheses are made regarding each of these questions. Furthermore, a preliminary model of tactile communication is presented based upon the literature on touch, as well as the conceptual framework outlined in the article.
Comparison of IgE Antibody Concentrations to Pyromellitic Dianhydride-Modified Laminin and Human Serum Albumin in Sera of Exposed Workers with Respiratory Complaints
Authors: Czuppon A.B. , Merget R. , Raulf-Heimsoth M. , Bruening T.
Published: April 2003

Background: Acid anhydrides are used in a variety of industrial branches because of their highly reactive anhydride groups. Adverse effects of anhydride exposure include toxic/irritative effects as well as IgE- and IgG-mediated respiratory disorders. It was the aim of this study to examine the usefulness of conjugates of pyromellitic dianhydride (PMDA) and laminin, a respiratory tract protein, for the in vitro diagnosis of sensitization to PMDA. Methods: Sera of PMDA-exposed workers (n = 9) and nonexposed controls (n = 8) were tested with an enzyme allergosorbent test (EAST). Human laminin and human serum albumin (HSA) were derivatized with PMDA and used as solid-phase in a commercial assay. Results: Seven out of 9 exposed workers revealed elevated IgE antibody concentrations (>0.35 kU/l) against laminin-PMDA whereas 5 of 9 subjects had elevated IgE antibody concentrations to HSA-PMDA. All 9 workers had elevated IgE antibody concentrations in at least one of the two tests. Of the 4 workers who complained of shortness of breath, 3 were positive for laminin-PMDA and 2 for HSA-PMDA. All of the nonexposed subjects were negative (<0.35 kU/l) for laminin-PMDA. Conclusion: PMDA-modified laminin could provide an additional diagnostic tool for the detection of sensitization to PMDA.
Mastocytosis and Fibrosis: Role of Cytokines
Authors: Li Chin-Yang , Baek Jin-Young
Published: April 2003

Mastocytosis is a rare stem cell disorder characterized by abnormal growth and accumulation of mast cells in one or more organ systems. Clinical heterogeneity is a hallmark of mastocytosis. Recent observations of activating mutations in c-kit may help to understand the abnormal growth of mast cells in mastocytosis. However, this mutation alone does not explain the entire clinical heterogeneity of the disease. Reticulin fibrosis is also commonly associated with systemic mastocytosis. Mast cells are known to be the source of fibrogenic cytokines, including platelet-derived growth factor, transforming growth factor-β (TGFβ) and basic fibroblast growth factor (bFGF). Immunohistochemical studies show a close correlation between the mast cell expression of bFGF and the reticulin fibrosis of mastocytosis lesions. The study of cytokine receptor expression also demonstrates that the TGFβ receptor I (RI)-negative cases of mastocytosis are prognostically less favorable than the TGFβRI-positive cases. This finding may be related to the fact that the TGFβR complex functions as a tumor suppressor gene in neoplastic cells.
Effectiveness of the MSC Cold Cap System in the Prevention of Chemotherapy-Induced Alopecia
Authors: Christodoulou C. , Klouvas G. , Efstathiou E. , Zervakis D. , Papazachariou E. , Plyta M. , Skarlos D.V.
Published: April 2003

Objective: To study the effectiveness of the MSC cold cap system to prevent chemotherapy-induced alopecia. Methods: The system was applied in 83 cancer patients (mean age 49.8 years) undergoing chemotherapy with alopecia-causing agents. Seven patients did not tolerate the system. Seventy-six patients were evaluable for assessment; 26 received anthracycline (group A), 33 taxane (group T), 5 anthracycline plus taxane (group AT), 7 intravenous etoposide (group E) and 5 ifosfamide with or without other alopecia-causing drugs (group I). In group A, 18 patients received conventional (subgroup Ac) and 8 high doses (subgroup Ah). In group T, 8 patients received docetaxel (subgroup D) and 25 paclitaxel (subgroup P). Alopecia grade 0–1 (Dean’s system) was considered as treatment success. Results: Grade 0–1 alopecia was achieved in 49/76 (64.5%) patients: group T 23/33 (69.6%), subgroup P 16/25 (64%) and subgroup D 7/8 (87.5%); group A 18/26 (69.2%), subgroup Ac 16/18 (88.8%) and subgroup Ah 2/8 (25%); group AT 1/5 (20%); group E 6/7 (85.7%), and group I 1/5 (20%). Conclusions: The MSC cold cap system is effective in preventing alopecia from anthracycline, etoposide or taxane but not from anthracycline-taxane combinations or ifosfamide-containing regimens.