bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Retinoic Acid Treatment on Cytogenetic Remission of Chronic Myeloid Leukaemia
Authors: Egyed Miklós , Kollár Balázs , Rumi György , Keller Éva , Vass János , Fekete Sándorné
Published: April 2003

The cytogenetic responses during the first chronic phase of 11 patients with chronic myeloid leukaemia (CML) treated with all-trans retinoic acid (ATRA) + interferon (IFN) were compared with those of 9 other CML patients treated with IFN alone. Metaphase and interphase cytogenetics and a semi-quantitative polymerase chain reaction were used to evaluate the cytogenetic responses. Two of the 11 patients in the ATRA + IFN group were withdrawn, one of them because of IFN intolerance, and the other because of non-compliance. Of the 9 remaining ATRA + IFN-treated patients 6 exhibited major cytogenetic responses, 3 of which were complete. Of the 9 patients treated with IFN alone, only 2 showed major cytogenetic responses. No severe adverse effects were observed. The preliminary results suggest that the ATRA + IFN combination may be superior in achieving cytogenetic remission in the first chronic phase of CML.
Therapeutic Promise of Embryonic Kidney Transplantation
Authors: Hammerman Marc R.
Published: April 2003

One novel solution to the shortage of human kidneys available for transplantation envisions ‘growing’ new kidneys in situ via xenotransplantation of renal anlagen. We and others have shown that developing metanephroi transplanted into animal hosts undergo differentiation and growth, become vascularized by blood vessels of host origin and exhibit excretory function. Metanephroi can be stored for up to 3 days in vitro prior to transplantation with no impairment in growth or function post-implantation. Metanephroi can be transplanted across both concordant (rat to mouse) and discordant/highly disparate (pig to rodent) xenogeneic barriers. Here we review studies exploring the potential therapeutic use of embryonic kidney transplantation.
Selective Cyclooxygenase-2 Inhibition Upregulates Renal Cortical αv Integrin Expression
Authors: Waldner Christoph , Heise Gunhild , Meyer-Kirchrath Jutta , Schrör Karsten , Grabensee Bernd , Heering Peter
Published: April 2003

Background: Cyclooxygenase-2 (COX-2), the inducible isoform of the cyclooxygenases, is upregulated in various inflammatory renal diseases and responsible for prostaglandin formation. As prostaglandins are known to influence cell adhesion processes, we investigated the effect of COX-2 inhibition on the expression of αv integrins, which are also enhanced in renal diseases and control the adherence between the endothelium and the extracellular matrix (ECM) in the glomerulus. Methods: Healthy female Wistar rats and animals with previously induced passive Heymann nephritis (PHN) received either 5 mg/kg body weight/day celecoxib or a placebo. After 28 days, renal cortical mRNA expression of COX-2 and αv integrin subunits was determined. Results: Rats with PHN showed a significant 1.7-fold increase in renal cortical mRNA expression of αv integrin subunits. Treatment with celecoxib increased cortical αv integrin mRNA expression 2.2-fold (p < 0.05) in healthy animals and 4.0-fold (p < 0.05) in rats with PHN, but lowered COX-2 mRNA expression in rats with PHN to 0.8-fold (p < 0.05). An inverse correlation between the expression of COX-2 and αv integrins in rats with PHN was demonstrated. Conclusions: It is suggested that COX-2-derived prostaglandins suppress the expression of αv integrins. This implies a previously unknown role for COX-2 in chronic inflammation in the kidney.
Serum Ratio of Heart-Type Fatty Acid-Binding Protein to Myoglobin
Authors: Furuhashi Masato , Ura Nobuyuki , Hasegawa Koichi , Yoshida Hideaki , Tsuchihashi Kazufumi , Nakata Tomoaki , Shimamoto Kazuaki
Published: April 2003

Background: The concentration of heart-type fatty acid-binding protein (hFABP), a promising novel marker for detection of acute or persistent myocardial damage, is significantly influenced by renal clearance and thus has limitations to its usefulness in patients with renal dysfunction. We evaluated whether the serum ratio of hFABP to myoglobin (F/M) might be a useful marker for assessing cardiac damage in hemodialysis patients. Methods: Serum hFABP and myoglobin were measured, and the value of F/M was calculated in 21 hemodialysis patients. Cardiac markers (cardiac troponin T [cTnT], atrial natriuretic peptide [ANP], and brain natriuretic peptide [BNP]) and echocardiographic indices (left ventricular end-diastolic dimension [LVDd], left ventricular mass index [LVMI], and inferior vena cava [IVC] dimension) were examined and compared with hFABP, myoglobin, and F/M ratios. Results: Serum hFABP and myoglobin levels were significantly elevated in hemodialysis patients and reduced by 30–40% during hemodialysis. The value of F/M after hemodialysis, but not the concentration of hFABP or myoglobin, had significant linear correlations with ANP, BNP, cTnT, LVDd, LVMI, and IVC. Conclusion: The value of F/M after hemodialysis, but not the concentration of hFABP itself, might be a newly useful marker for estimation of cardiac damage and volume overload in hemodialysis patients.
Localization, cDNA sequence and genomic organization of the rat seipin gene (Bscl2) and sequence analysis in inbred rat models of Type 2 diabetes mellitus
Authors: Kaisaki P.J. , Sebag-Montefiore L.M. , Brown J.H. , Magre J. , Lathrop M. , Capeau J. , Gauguier D.
Published: April 2003

Mutations in the gene encoding seipin cause Berardinelli-Seip congenital lipodystrophy 2, with symptoms including near-absence of adipose tissue and altered glucose tolerance. Radiation hybrid analysis localized the seipin gene (Bscl2) in rat to a major quantitative trait locus in rat chromosome 1 linked to glucose intolerance in the Goto-Kakizaki (GK) rat model of Type 2 diabetes. We determined the genomic organization of Bscl2 and screened coding exons and flanking intron sequences for mutations in GK, Wistar and Brown Norway rats, as well as in the Otsuka Long-Evans Tokushima Fatty (OLETF) diabetic rat. Two silent single nucleotide polymorphisms that were identified also were found in non-diabetic rat strains. We conclude that mutations in the gene for seipin are unlikely to contribute to diabetes in GK and OLETF rats.
Mechanisms Involved in Glucagon-Like Peptide-1 (7–36) Amide Action on the Rat Hypothalamo-Neurohypophysial System
Authors: Bojanowska Ewa , Stempniak Bozena
Published: April 2003

Glucagon-like peptide-1 (7–36) amide (tGLP-1) has been shown to modify the secretory function of the rat hypothalamo-neurohypophysial complex (HNC). However, mechanisms underlying this action are still unclear. Using explants containing the HNC obtained from euhydrated rats, possible interactions of tGLP-1 with angiotensin II (Ang II), forskolin-induced cAMP synthesis or calcium ions were investigated. In addition, explants taken from rats given 2% saline were used in order to examine whether chronic osmotic stimulation affects tGLP-1 action on vasopressin and oxytocin neurons. tGLP-1 did not modify Ang II- or forskolin-evoked hormone release. Incubation of the HNC in calcium-free medium inhibited the tGLP-1-dependent vasopressin/oxytocin secretion. Prolonged salt loading in vivo completely changed the neurohypophysial response to tGLP-1 in vitro; it did not only abolish the stimulatory effect of tGLP-1 on basal hormone release, but reduced K+-stimulated vasopressin/oxytocin secretion. Consequently, the neurohypophysial response to tGLP-1 may depend on the functional status of the HNC and on the presence of calcium ions, but not cAMP.
Unexpected Expansive Paranasal Sinus Mucormycosis
Authors: Larsen Kristian , Buchwald Christian von , Ellefsen Bjarki , Francis Dorthe
Published: April 2003

Mucormycosis infection of the paranasal sinuses is a very rare but serious condition. Patients are usually immunocompromised by systemic disease. We report an unexpected case of expansive paranasal sinus mucormycosis in an immunocompetent European treated successfully with surgical debridement and intravenous amphotericin B. The pathogenesis, diagnosis and treatment of paranasal sinus mucormycosis is discussed.
Lines of Evidence on the Risks of Suicide with Selective Serotonin Reuptake Inhibitors
Authors: Healy David
Published: April 2003

Background: There has been a long-standing controversy about the possibility that selective serotonin reuptake inhibitor (SSRI) antidepressants might induce suicidality in some patients. Methods: Starting from the clinical studies that gave rise to this issue, this paper reviews an unselected cohort of randomized clinical trials (RCTs), a series of meta-analyses undertaken to investigate aspects of the problem, studies in recurrent brief depressive disorders, epidemiological studies and healthy volunteer studies using SSRIs to shed light on this issue. Results: The original clinical studies produced evidence of a dose-dependent link, present on a challenge, dechallenge and rechallenge basis, between SSRIs and both agitation and suicidality. Meta-analyses of RCTs conducted around this time indicate that SSRIs may reduce suicidal ideation in some patients. These same RCTs, however, yield an excess of suicides and suicide attempts on active treatments compared with placebos. This excess also appears in the best-controlled epidemiological studies. Finally, healthy volunteer studies give indications that SSRIs may induce agitation and suicidality in some individuals. Conclusions: The data reviewed here, which indicate a possible doubling of the relative risk of both suicides and suicide attempts on SSRIs compared with older antidepressants or non-treatment, make it difficult to sustain a null hypothesis, i.e. that SSRIs do not cause problems in some individuals to whom they are given. Further studies or further access to data are indicated to establish the magnitude of any risk and the characteristics of patients who may be most at risk.
Metagenomes of Complex Microbial Consortia Derived from Different Soils as Sources for Novel Genes Conferring Formation of Carbonyls from Short-Chain Polyols on Escherichia coli
Authors: Knietsch Anja , Waschkowitz Tanja , Bowien Susanne , Henne Anke , Daniel Rolf
Published: April 2003

Metagenomic DNA libraries from three different soil samples (meadow, sugar beet field, cropland) were constructed. The three unamplified libraries comprised approximately 1,267,000 independent clones and harbored approximately 4.05 Gbp of environmental DNA. Approximately 300,000 recombinant Escherichia coli strains of each library per test substrate were screened for the production of carbonyls from short-chain (C2 to C4) polyols such as 1,2-ethanediol, 2,3-butanediol, and a mixture of glycerol and 1,2-propanediol on indicator agar. Twenty-four positive E. coli clones were obtained during the initial screen. Fifteen of them contained recombinant plasmids, designated pAK201–215, which conferred a stable carbonyl-forming phenotype on E. coli. Sequencing revealed that the inserts of pAK201–215 encoded 26 complete and 14 incomplete predicted protein-encoding genes. Most of these genes were similar to genes with unknown functions from other microorganisms or unrelated to any other known gene. The further analysis was focused on the 7 plasmids (pAK204, pAK206, pAK208, and pAK210–213) recovered from the positive clones, which exhibited an NAD(H)-dependent alcohol oxidoreductase activity with polyols or the correlating carbonyls as substrates in crude extracts. Three genes (orf6, orf24, and orf25) conferring this activity were identified during subcloning of the inserts of pAK204, pAK211, and pAK212. The sequences of the three deduced gene products revealed no significant similarities to known alcohol oxidoreductases, but contained putative glycine-rich regions, which are characteristic for binding of nicotinamide cofactors.
Orbital Metastasis from Prostatic Carcinoma
Authors: Baltogiannis Dimitrios , Kalogeropoulos Christos , Ioachim Elli , Agnantis Niki , Psilas Konstantinos , Giannakopoulos Xenofon
Published: April 2003

A rare case of orbital metastasis from carcinoma of the prostate in a 76-year-old man who presented with pain in his left eye, mild proptosis and reduced visual acuity is reported. Cranial CT scanning demonstrated large bone metastases in the left orbit. The patient underwent orbital evisceration. The histopathological studies that were based on the morphological and immunohistochemical findings confirmed the histological diagnosis of orbital metastasis arising from prostatic carcinoma with neuroendocrine features.
Incisional Hernia after Suprapubic Trocar Cystostomy
Authors: Nabi Ghulam , Aron Monish , Gupta Narmada P.
Published: April 2003

A 25-year-old male with an incisional hernia following suprapubic trocar cystostomy for a failed traumatic perurethral catheterization is presented. This is only the 2nd case reported in the literature. Pathophysiology and management of this rare complication are discussed.
Identification and Quantification of Antigens Associated with HLA Class I Molecules on a Bladder Tumour Cell Line
Authors: Torabi-Pour Nasir , Morrow W. John W. , Saffie Roghieh , Gowda Prashant G. , Perrett D. , Oliver Timothy R.D.
Published: April 2003

The aim of this study was to isolate and identify antigenic peptides associated with HLA class I molecules on a bladder tumour cell line. HLA-A1 moelcules were purified using an immunobead-purification technique and following elution of nonapeptides associated with the complex, their HPLC profile was determined by Tandem mass spectrometry (MS/MS). Three peptides were identified namely: (1) P991 (VTDPGNLLY); (2) P1041.5 (LTDLGFLVY), and (3) P1057.7 (LTDPHLLSY); these sequences matched elements of hepatitis B, MAGE1-A1 and herpes simplex viruses. These antigens had half-lives of approximately 120 min which is within the theoretical range of such short peptides. These results indicate that identification of MHC-associated peptides is possible without using an assay for cytotoxic T cells. Although this approach was applied on a relatively small scale, broader applications can be foreseen.
Value of Diffusion-Weighted Imaging in Patients with a Nonlocalizing Examination and Vasospasm from Subarachnoid Hemorrhage
Authors: Phan Thanh G. , Huston, III John , Campeau Norbert G. , Wijdicks Eelco F.M. , Atkinson John L.D. , Fulgham Jimmy R.
Published: April 2003

We evaluated the value of diffusion-weighted imaging (DWI) in patients with suspected vasospasm from subarachnoid hemorrhage (SAH). Magnetic resonance imaging (MRI), including DWI, was performed in 5 patients with vasospasm resulting from SAH. Restricted diffusion (ischemia) was present in 3 patients with symptomatic vasospasm. A diffusion abnormality was not demonstrated in 2 patients with asymptomatic vasospasm despite persistently elevated velocities by transcranial Doppler ultrasonography in 1. In this patient, serial MRI studies showed no ischemia. Our results suggest that DWI may provide a method to assess the presence and severity of ischemia in patients with SAH and vasospasm and assist in patient management.
Is Ultrasound Examination Sufficient in the Evaluation of Patients with Internal Carotid Artery Severe Stenosis or Occlusion?
Authors: Paciaroni Maurizio , Caso Valeria , Cardaioli Gabriela , Corea Francesco , Milia Paolo , Venti Michele , Hamam Mohammed , Pelliccioli Gian Piero , Parnetti Lucilla , Gallai Virgilio
Published: April 2003

Background and Purpose: Carotid endarterectomy (CE) has been shown to be beneficial in patients with symptomatic high-grade internal carotid artery (ICA) stenosis. Some authors have suggested that when ultrasound shows a stenosis 70–99%, CE can be performed without further imaging study. However, ultrasound findings that suggest an ICA occlusion, not confirmed by angiography but which instead show a near-occlusion usually benefit from CE. The objectives of this study are: (1) to evaluate how angiography-obtained information on intracranial arteries affects the treatment decision in patients with 70–99% ICA stenosis, and (2) to evaluate when a symptomatic ICA occlusion shown by ultrasound could actually be a patent artery and therefore benefit from CE. Materials and Methods: We prospectively collected the cerebral angiograms of 133 consecutive patients with TIA or non-disabling stroke due to large artery disease where ultrasound suggested a stenosis ≧70% or occlusion of symptomatic ICA; we calculated the frequency of intracranial vascular malformations and intracranial artery disease (IAD) located in the infraclinoid or supraclinoid portion of the ICA, and in the anterior or middle cerebral artery. Results: Ultrasound showed 31 ICA occlusions and 102 ICA with 70–99% stenosis. All the patients with an ICA stenosis 70–99% on ultrasound examination had the degree of stenosis confirmed by angiography. Two out of 31 patients did not have a complete occlusion but angiography showed a near-occlusion and consequently they underwent CE. Sixty-five (62.5%) out of 104 patients with patent ICA had IAD (mild 26.9%, moderate 21.2%, and severe 14.4%). Five patients (4.8%) had intracranial vascular malformations (4 aneurysms and 1 arteriovenous malformation). One patient had disabling stroke during angiography. Seven patients (6.7%) did not undergo CE after angiography (1 patient had an aneurysm >10 mm, 1 patient had a very tight stenosis of the basilar artery, 5 patients had intracranial stenosis more severe than the extracranial stenosis). Conclusions: In patients that on the basis of ultrasound examination can benefit from CE, information on intracranial arteries is necessary. Moreover, complete occlusion cannot be detected with certainty only by ultrasound examination.
Do Obsessive-Compulsive Patients and Abstinent Heroin Addicts Share a Common Psychophysiological Mechanism?
Authors: Papageorgiou Charalabos , Rabavilas Andreas , Liappas Ioannis , Stefanis Costas
Published: April 2003

Background/Aim: Working memory (WM) and attentional deficits have been implicated in the pathophysiology of both obsessive-compulsive disorder (OCD) and opioid addiction. The P300 component of event-related potentials (ERPs) is considered as an index of on-line updating of WM and/or attentional operations involved in this function. The present study aimed at comparing the P300 elicited during a WM test in patients with prolonged heroin abstinence, those with OCD and healthy controls, in order to demonstrate possibly common underlying psychophysiological mechanisms. Methods: The P300 component was evaluated during the anticipatory period of a WM test in 20 patients characterized by a past history of opioid dependence (6 months abstinence), in 18 OCD patients, and 20 healthy subjects matched for age, sex and educational level. Results: The two patient groups showed a considerable reduction of the P300 amplitudes, located at the right frontal area as compared with healthy controls. The abstinent heroin addicts exhibited a significantly lower P300 amplitude at central frontal areas and a significantly higher P300 amplitude at the left occipital region relative to the other two groups. Furthermore, the abstinent group showed a notable delay of P300 latency relative to controls and OCD patients at the right occipital region. Moreover, the OCD patients manifested a significant prolongation of P300 located at the central prefrontal area, relative to addicts and healthy controls. Conclusions: These findings point to considerable WM and/or attentional deficits in the long-term abstinent syndrome of heroin misuse and OCD associated with distributed and prefrontal cortical circuits, respectively. Furthermore, the present findings suggest that both OCD and long-term abstinent heroin addicts may share a common impairment of WM and/or attention involving or affecting the right prefrontal areas.
Jealousy and Subthreshold Psychopathology: A Serotonergic Link
Authors: Marazziti Donatella , Rucci Paola , Di Nasso Elena , Masala Irene , Baroni Stefano , Rossi Alessandra , Giannaccini Gino , Mengali Francesco , Lucacchini Antonio
Published: April 2003

Background: A few studies suggest that different neurotransmitters may play a role in the expression of jealousy. Our study aimed to explore the serotonergic system by means of the specific binding of 3H-paroxetine (3H-Par) to platelet membranes of healthy subjects with and without excessive jealousy concerns, according to a specific self-administered questionnaire [Questionnaire for affective relationships (QAR)]. Subjects and Methods: The study sample includes 21 subjects concerned by jealousy thoughts and 21 control subjects without jealousy concerns, as shown by their QAR scores. Subjects of the first group were administered a battery of self-report instruments designed to detect the presence of typical, atypical and subthreshold psychopathology. Platelet membranes and 3H-Par binding were carried out according to standardized protocols. Results: Subjects with excessive jealousy concerns had a reduced density of 3H-Par binding as compared with control subjects without jealousy concerns and had one or more psychiatric spectrum conditions. Conclusions: Our findings suggest that excessive jealousy is associated with various forms of psychopathology and may be underlain by alteration of the serotonergic system, as reflected by the lower density of the platelet serotonin transporter.
CIAS1 Mutation in a Patient with Overlap between Muckle-Wells and Chronic Infantile Neurological Cutaneous and Articular Syndromes
Authors: Granel B. , Philip N. , Serratrice J. , Ene N. , Grateau G. , Dodé C. , Cuisset L. , Disdier P. , Berbis P. , Delpech M. , Weiller P.J.
Published: April 2003

The Muckle-Wells syndrome is a rare autosomal dominant disorder belonging to the group of hereditary fever syndromes. The chronic infantile neurological cutaneous and articular (CINCA) syndrome is a systemic inflammatory disorder of unknown etiology with neonatal onset. They are considered as two different entities. We report the case of a 36-year-old man suffering since birth from a nonpruritic generalized urticaria, with inflammatory flares, joint manifestations and progressive deafness requiring a bilateral hearing aid. An initial diagnosis of Muckle-Wells syndrome was made. However, the patient had an unusual clinical presentation with slightly dysmorphic facial appearance, clubbing of the fingers, mild mental retardation and papilledema. After a genetic advice, a diagnosis of CINCA syndrome was made. Search for mutations in the CIAS1 gene revealed a new mutation in a heterozygous state. This case report really raises the question of a link between these two inflammatory diseases. Further studies are needed to confirm the involvement of mutations of the CIAS1 gene in CINCA syndrome.
Effect of Different Doses of Vitamin E on the Incidence of Malformations in Pregnant Diabetic Rats
Authors: Viana Marta , Castro Mario , Barbas Coral , Herrera Emilio , Bonet Bartolome
Published: April 2003

Background/Aims: Previously we have shown that administration of 150 mg of vitamin E (α-tocopherol) per day to rats having diabetes decreases the rate of embryo malformations and increases their maturation and size. The present study was addressed to determine the effects of different doses of vitamin E upon these parameters. Methods: Female rats were made diabetic (D) with streptozotocin, and from day 0 of gestation they were treated daily with 25 (D+25), 50 (D+50), 100 (D+100), 150 (D+150), and 500 (D+500) mg of vitamin E administered orally and were compared with control (C) animals. Results: On day 11.5 of gestation, crown-rump length, somite number, and protein and DNA levels were lower in D than in C embryos. Crown-rump length and somite number increased with 100 mg or higher doses of vitamin E, although the values observed in C embryos were not reached. The proportions of reabsorption and malformations were 24.7 and 50%, respectively, in D rats, and in the rats supplemented with vitamin E they decreased to 22.7 and 19% in D+25, 16.4 and 21.3% in D+50, 16.2 and 12% in D+100, 12.9 and 13.9% in D+150, and to 43.9 and 10.8% in D+500 rats, whereas the values were 6.8 and 4.9% in C animals. Conclusions: Administration of vitamin E to D rats decreases the rate of embryo malformations, dependent on the dose administered. However, high doses have a negative effect in the conceptus, as shown by the increased rate of reabsorptions in the D+500 group.
Quantity and Quality of Dietary Fat, Carbohydrate, and Fiber Intake in the German EPIC Cohorts
Authors: Linseisen Jakob , Schulze Matthias B. , Saadatian-Elahi Mitra , Kroke Anja , Miller Anthony B. , Boeing Heiner
Published: April 2003

Aim: This evaluation aims to describe the quantity and quality of dietary fat, carbohydrate and fiber intake in both German cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: Estimates are based on standardized computer-guided 24-hour dietary recalls from 1,078 women and 1,013 men in Heidelberg and 898 women and 1,032 men in Potsdam. In a subsample, plasma phospholipid (PL) fatty acids were analyzed as well. Results: Adjusted mean dietary intake estimates demonstrated that the contribution of fat as well as n–6 and n–3 polyunsaturated fatty acids (PUFA) to the total daily energy intake was higher in both women and men of EPIC-Potsdam compared to EPIC-Heidelberg. Surprisingly, the dietary n–6/n–3 PUFA ratio was lower in the Potsdam cohort. These results were confirmed by means of the PL fatty acid pattern. Besides the higher contribution of polysaccharides to total energy intake in EPIC-Heidelberg, women of the Heidelberg cohort revealed a significantly lower contribution of mono- and disaccharides (sucrose) to total energy intake. Although total fiber intake data were similar in both cohorts, analysis by food groups showed differences in dietary fiber intake originating from the food groups cereals, fruits and potatoes. Conclusion: The results demonstrate distinct differences in the dietary fat, carbohydrate and fiber intake between both German EPIC cohorts, which contribute to the exposure variation in the whole of EPIC.
Deep Brain Stimulation for Dystonia
Authors: Coubes Philippe , Vayssiere Nathalie , El Fertit Hassan , Hemm Simone , Cif Laura , Kienlen Jacques , Bonafe Alain , Frerebeau Philippe
Published: April 2003

Stimulation electrodes are implanted under general anesthesia, without intra-operative electrophysiology or clinical testing, based only on stereotactic MRI and direct anatomical localization of the postero-ventro-basal GPi. We retrospectively analyzed the surgical procedure that has been designed and implemented in our center, using the Leksell G frame, for initiating deep brain stimulation in 65 dystonic patients. We report the surgical technique and the hardware and software complications. We recommend immediate postoperative stereotactic MRI under general anesthesia as a prerequisite to check the reliability of MR acquisition (magnet stability) and the exact localization of each electrode. This technique allowed us to reduce the duration of the operation to 4 h, including general anesthesia, frame fixation, MRI acquisition, implantation of two electrodes under radioscopic control, immediate postoperative stereotactic MRI and frame removal. Surgery-related morbidity was very low with a 0% hemorrhage rate and three delayed unilateral infections re-operated 6 months later. Hardware and software complications were rare. The advances in 3D-MR imaging permit the electrode implantation for deep brain stimulation without resorting to intraoperative localization techniques, which is especially helpful in children and for treating dystonia. The maximum follow-up period is 58 months (first case: November 1996). GPi stimulation has proven to be an effective treatment for most dystonic syndromes with particular efficacy in the disease due to the DYT1 mutation.
Deep Brain Stimulation for Dystonia in Adults
Authors: Krauss Joachim K.
Published: April 2003

The renaissance of functional neurosurgery in the treatment of Parkinson’s disease has sparked also the interest in other movement disorders which are refractory to medical treatment. Deep brain stimulation (DBS) has been used only since a few years in dystonia patients. This review summarizes the available data on pallidal and thalamic DBS for various dystonic syndromes. The major advantage of DBS as compared to radiofrequency lesioning is that it allows performing contemporaneous bilateral surgery with relatively low morbidity in these patients. The posteroventral lateral globus pallidus internus (GPi) has been the preferred target in most instances, thus far. While phasic dystonic movements may improve early after surgery, the response of tonic dystonic movements to chronic stimulation may be delayed. The most beneficial results have been achieved in patients with primary genetic generalized and segmental dystonia, myoclonic dystonia, and complex cervical dystonia. Outcome has been varied in patients with other dystonic disorders, in particular those with secondary dystonia. Most studies have reported on relatively short follow-up periods, on single cases, or were retrospective. Pallidal DBS has been shown to be effective in complex cervical dystonia yielding both symptomatic and functional benefit for up to 2.5 years of follow-up. Dramatic improvement has been obtained in children and in adults with DYT1 positive dystonia. Also, patients with non DYT1 genetic dystonia achieved sustained benefit for up to 2 years of follow-up. Preliminary experience indicates that choreoathetosis in patients with cerebral palsy responds less well to pallidal DBS, and that it may not be effective at all in some patients. In single instances unilateral pallidal DBS has been shown to yield valuable benefit in patients with hemidystonia. The experience with DBS for treatment of Meige syndrome and other focal dystonias has been explored only recently. There is much less experience with thalamic DBS for dystonia. Thalamic DBS has been shown to be effective in single cases with posttraumatic dystonia, postanoxic dystonia and paroxysmal nonkinesigenic dystonia. Future perspectives of DBS for treatment of dystonia include the development of new technology, the evaluation of the possible role of other targets, and carefully planned studies to further establish the role of surgery.
Metabolic Control as a Modifier of the Association between Salivary Factors and Dental Caries among Diabetic Patients
Authors: Syrjälä Anna-Maija H. , Niskanen Mirka C. , Ylöstalo Pekka , Knuuttila Matti L.E.
Published: April 2003

The aim here was to analyze the role of metabolic control as a modifier of the association of salivary factors with dental caries among diabetic patients. Cross-sectional data were gathered from 149 insulin-dependent diabetes mellitus patients by means of clinical examination, a quantitative questionnaire and patient records. Dental caries was measured as the number of decayed surfaces. The data were analyzed using negative binomial regression models. HbA1c level appeared not to be associated with dental caries. Of the salivary factors, only high levels of mutans streptococci (MS) and lactobacilli were associated with dental caries. Among the subjects with HbA1c ≧8.5, the presence of dental caries was more distinctly associated with higher levels of MS (RR = 3.86, CI: 1.39–11.96) and lactobacilli (RR = 3.59, CI: 1.44–9.33) compared to those with HbA1c <8.5. It can be concluded that poor glycemic control strengthens the positive association of MS and lactobacilli with dental caries.
Inhibition of nNOS and iNOS following Hypoxia-Ischaemia Improves Long-Term Outcome but Does Not Influence the Inflammatory Response in the Neonatal Rat Brain
Authors: van den Tweel Evelyn R.W. , Peeters-Scholte Cacha M.P.C.D. , van Bel Frank , Heijnen Cobi J. , Groenendaal Floris
Published: April 2003

In this study, we tested the hypothesis that combined inhibition of nNOS and iNOS will reduce neuronal damage and the inflammatory response induced by perinatal hypoxia-ischaemia (HI). In 12-day-old rats, HI was induced by right carotid artery occlusion followed by 90 min of 8% O2. Immediately upon reoxygenation, the rats were treated with NOS inhibitors (n = 24) or placebo (n = 24). Neuropathology was scored at 6 weeks after HI on a 4-point scale (n = 12 per group). The expression of heat shock protein 70 (HSP70) and mRNA expression for cytokines were measured 12 h after HI (n = 12 per group). Histopathological analysis showed that the ipsilateral hemisphere in the NOS inhibition group was less damaged than in the placebo group (p < 0.05). HI induced a significant increase in HSP70 levels (p < 0.05) in the ipsilateral hemispheres, which tended to be lower in the NOS inhibition group (p = 0.07). HI induced an increase in mRNA expression for IL-1β, TNF-α and TNF-β, but there was no difference between the ipsi- and contralateral hemispheres. Combined inhibition of nNOS and iNOS did not induce any change in cytokine expression. We conclude that the long-term neuroprotective effects of combined nNOS and iNOS inhibition were not achieved by an altered cytokine response.
Early Appearance of Functional Deficits after Neonatal Excitotoxic and Hypoxic-Ischemic Injury: Fragile Recovery after Development and Role of the NMDA Receptor
Authors: Felt Barbara T. , Schallert Timothy , Shao Jie , Liu Yiqing , Li Xiaoling , Barks John D.E.
Published: April 2003

We sought to determine whether neonatal rats that sustain unilateral cerebral hypoxic-ischemic or excitotoxic insults (1) manifest contralateral sensorimotor deficits during development or in adulthood and (2) recover from those deficits. Seven-day-old (P7) rats received a right intrastriatal injection of the glutamate analog N-methyl-D-aspartate (NMDA). Unilateral hypoxia-ischemia (HI) was induced by right carotid ligation followed by 1.5 h in 8% O2. Both procedures produce neuronal loss in the striatum and sensorimotor cortex. Nonlesioned controls were included. We scored percent forepaw placement on the edge of a horizontal surface, with lateral vibrissa stimulation, from P9 to P19, and at P33 and P50. Then, on P50, rats were treated with the NMDA antagonist MK-801 to determine whether deficits could be reinstated. NMDA- and HI-lesioned rats exhibited a deficit in contralateral vibrissa-stimulated forepaw placing that emerged during the second week of life. Yet, by P33 and P50, the lesioned groups and controls were indistinguishable. MK-801 injection on P50 resulted in transient reinstatement of the placing deficit. After unilateral neonatal excitotoxic or HI brain injury, contralateral sensorimotor deficits are detected, but in many animals, these deficits have resolved by adulthood. Thus, timing of sensorimotor tests may influence their sensitivity for detection of focal neuropathology originating in the neonatal period.
New Approaches to Brain Injury in Preterm Infants
Authors: Edwards David
Published: April 2003

Preterm birth is strongly associated with neurodevelopmental impairment, but the causes of cerebral injury are not completely understood. It is often assumed that damage is due to cerebral hypoxia-ischemia secondary to the extreme stresses induced by prolonged intensive care. However, the primary role of reduced cerebral blood flow is questioned by the findings of several studies that normal cerebral blood flow can be as low as 5–10 ml/100 g–1/min–1 in infants who have normal neurological outcome [1, 2]. Indeed, some commonly used drugs, particularly indomethacin, but also aminophylline, cause significant falls in cerebral blood flow without any clear evidence that they lead to cerebral injury [3, 4].
Comparative Single-Dose Pharmacokinetics of Clonazepam following Intravenous, Intramuscular and Oral Administration to Healthy Volunteers
Authors: Crevoisier C. , Delisle M.C. , Joseph I. , Foletti G.
Published: April 2003

The objective was to assess the single-dose pharmacokinetics of clonazepam following i.m., p.o. and i.v. administration. In an open-label, three-way crossover study, 12 healthy volunteers were randomized to receive a single dose of 2 mg clonazepam either by the i.m., p.o. or i.v. route. Serial blood samples were collected up to 120 h after drug administration. Plasma concentrations of clonazepam were determined by electron-capture gas-liquid chromatography. The absorption rates of clonazepam after i.m. and p.o. administration of clonazepam were significantly different from each other, as reflected by the respective mean values of maximum plasma concentration (Cmax 11.0 vs. 14.9 ng·ml–1) and time to reach maximum concentration (tmax 3.1 vs. 1.7 h). Secondary plasma peaks of clonazepam were observed in 9 volunteers after i.m. injection (Cmax 9.9 ng·ml–1; tmax 10.4 h). A comparison of the area under the plasma concentration-time curves (AUC) shows that the i.m. route is equivalent to the oral route (AUC0–∞ 620 vs. 561 ng·h·ml–1). Clonazepam was almost completely absorbed after i.m. and p.o. administration, as shown by the mean absolute bioavailability of 93 and 90%, respectively. No significant differences existed between the elimination half-lives (i.v. 38.0 h; i.m. 43.6 h; p.o. 39.0 h). The average clearance and volume of distribution (VZ) were 55 ml·min–1 and 180 liters, respectively. In conclusion, the observed differences in Cmax and tmax after i.m. and p.o. administration were consistent with a slower absorption rate of clonazepam after i.m. injection. The systemic exposure to clonazepam was not affected by the route of extravascular administration. Statistical evaluation of these kinetic data showed differences in the absorption rate, so that clonazepam given by the i.m. route is not bioequivalent to the oral route. On the basis of the results of this study, we would recommend the same i.m. and p.o. dose in epileptic patients, but therapeutic response would be expected to be less predictable and to occur later in the case of i.m. administration.
Surgical Treatment and Follow-Up of Pulmonary Hydatid Cyst
Authors: Ayed Adel K. , Alshawaf Emad
Published: April 2003

Objective: To report our experience of surgical procedures in the management of hydatid cysts of the lung and to assess the effect of postoperative chemotherapy. Subjects and Methods: In a longitudinal cohort study, 64 consecutive patients who presented with hydatid cysts of the lung from 1994 to 1998 were included. The main measures were: characteristics on presentation, operative techniques, postoperative morbidity, and the outcome of treatment. The mean age was 28 years (range 4–65 years). The most common symptoms were cough, chest pain, fever, and hemoptysis. Chest radiographs and computed tomograms were the main method of diagnosis. Pulmonary cystotomy and capitonnage were performed in 46 patients. Pulmonary resection was needed in 8 of 64 patients. Simultaneous combined resection of hydatid cysts through thoracotomy with transdiaphragmatic removal of liver cysts was performed in one stage in 13 patients. Results: Chest radiographs and CT scans showed a smoothly outlined spherical opacity in 45 patients. Other radiographic findings included ill-defined shadow (in 8 patients), pleural effusion (7 patients), air fluid level (3 patients), and hydropneumothorax in a single patient. There were 8 (12.5%) cases of immediate postoperative complications. These occurred mostly in patients who had cysts larger than 10 cm (p = 0.003). Thirty-four patients were treated by a 3-month course of albendazole chemotherapy. Four patients (6%) had recurrences of the disease during the follow-up period. These recurrences occurred in patients with large cysts >10 cm (p = 0.001). Conclusion: Conservative surgical methods are the preferred surgical techniques. Postoperative chemotherapy with albendazole for 3 months is recommended.
Patients on Chronic Hemodialysis Have No Intrinsic Lymphocyte Defect upon Stimulation with Interleukin-2, Interleukin-15 or Tumor Necrosis Factor-Alpha
Authors: van Riemsdijk I.C. , Baan C.C. , Loonen E.H.M. , Zietse R. , Weimar W.
Published: April 2003

Background: Patients on chronic hemodialysis (HD) suffer from general immune incompetence, resulting in a high incidence of infectious complications, impaired response to vaccinations and a high incidence of malignancy. Although various abnormalities in T cell function of HD patients have been described, it remains unclear whether this is due to an intrinsic T cell defect. Aim: In the present study we tested the capacity of T cells to proliferate upon stimulation with antigen-presenting cell and T-cell-derived cytokines. Methods: The proliferation capacity of lymphocytes obtained from patients on HD and healthy controls was determined by measuring the proliferation of peripheral blood mononuclear cells (PBMC) after stimulation with rhIL-2, rhIL-15, rhTNF-α, or combination of those cytokines. In all samples the percentage of α/β TCR-positive T cells was measured. Results: After isolation of PBMC the percentage of T cells varied from 70% (before stimulation) to 80% (after stimulation). IL-2, IL-15 and TNF-α all induced PBMC proliferation, while the combination TNF-α plus IL-2 or TNF-α plus IL-15 appeared to be additive. No difference between PBMC from HD patients and controls was found. Conclusion: We conclude that lymphocytes from HD patients have no intrinsic defects in their proliferation capacity after stimulation with IL-2, IL-15 or TNF-α, in vitro, as the increase in counts per minute is predominant.
Multizentrische Umfrage zum Stellenwert der Lymphonodektomie beim Endometriumkarzinom in Deutschland
Authors: Sehouli Jalid , Camara Oumar , Stengel Dirk , Köhler Günter , Lichtenegger Werner
Published: April 2003

Einleitung und Fragestellung: Im Management des Endometriumkarzinoms hat sich das primär chirurgische Staging etablieren können. Hierbei wird von verschiedenen Arbeitsgruppen auch die Lymphonodektomie empfohlen. Im Gegensatz zur prognostischen Bedeutung des Lymphknotenstatus ist der therapeutische Nutzen der Lymphonodektomie unklar. Methodik: Im Rahmen einer Querschnittsstudie im Zeitraum von Oktober 2001 bis Januar 2002 wurden insgesamt 1030 standardisierte Fragebögen an Frauenkliniken in Deutschland versendet. Ergebnisse: 595 Antworten (58%) konnten ausgewertet werden. Die Zusammensetzung war wie folgt: Universitätskliniken 5,2%, Kliniken der Maximalversorgung 69,7% und Regelversorgung 25%. Führen Sie eine Lymphonodektomie beim Endometriumkarzinom durch? Nur 7,3% (95% Kl: 5,3–9,7%) gaben an, nie eine Lymphonodektomie durchzuführen, 62,9% (95 Kl: 58,9–66,9%) führen diese in ausgewählten Fällen, 29,7% (95% Kl: 26–33.7%) regelmässig durch. Welche Methode der Lymphonodektomie wenden Sie an? 27,1% (95 Kl: 23,2–31,4%) setzen das «Sampling», 72,9% (95 Kl: 68,6–76,8%) die systematische Entfernung ein. 26,6% (95% Kl: 22,8–30,6%) lymphonodektomieren sowohl pelvin als auch paraaortal. Welche Intention verfolgen Sie mit der Lymphonodektomie? 31,7% (95% Kl: 22,8–30,6%) führen diese aus Gründen des Stagings, 3,1% (95% Kl: 1,8–4,9%) wegen des Überlebens und 65,2% (95% Kl: 60,9–69,3%) wegen beidem durch. 94,5% (95% Kl: 92,1–96,3%) gaben an, dass der Lymphknotenbefall einen Einfluss auf die Wahl der adjuvanten Behandlung besitzt. 76,8% (95% Kl: 72,8–80,4%) bzw. 36,9% (95 Kl: 46,9–56.5%) wählen in den Stadien I/II bzw. III/IV eine Radiotherapie, 20,4% (95% Kl: 16,9–24,2%) bzw. 51,7% (95% Kl: 46,9–56.5%) eine Radiochemotherapie. Schlussfolgerungen: Die vorliegenden Ergebnisse sollten als Grundlage für die Konzeption prospektiver, multizentrischer Studien zum operativen und zytostatischen Management dienen.
Influence of Apolipoprotein E Polymorphism on Cardiovascular Risk Factors in Obese Children
Authors: Guerra António , Rego Carla , Castro Elizabete M.B. , Seixas Susana , Rocha Jorge
Published: April 2003

Aim: The main objective of the study was to determine whether risk factors associated with obesity are influenced by genetic variation of apolipoprotein E (ApoE). Methods: 81 obese children (mean age 9.4 ± 2.8 years) and an age-matched control group were included. Body composition, lipid profile, and glucose and insulin levels were evaluated according to international recommendations, and the blood pressure was measured by an oscillometric method. Results: The calculated frequencies of the ApoE alleles *2, *3, and *4 (0.04, 0.88 and 0.08) in obese children were similar to those of eutrophic age-matched controls (0.07, 0.82, and 0.11) and fitted the range of variation generally observed in southern European populations. Age, anthropometric parameters, body fat mass, and blood pressure were similar in E2/3, E3/3 and E4/3 genotypes. Total/high-density lipoprotein cholesterol and low-density lipoprotein/high-density lipoprotein cholesterol ratios were higher in the E4/3 group as compared with E3/3 (p < 0.01) and E2/3 (p < 0.05) groups. No differences concerning clusters of risk factors were observed among the three genotypes. No associations were found between ApoE polymorphism and glucose levels (fasting and at 2 h) and between fasting insulin levels and HOMAIR results. Higher levels of fasting and 2-hour insulin and higher HOMAIR values were significantly associated with a higher fat mass. Conclusions: ApoE polymorphism seems to influence some lipid profile abnormalities associated with obesity in childhood. However, clustering of risk factors and insulin resistance seem not to be dependent on ApoE polymorphism.
A Computational Model for Neocortical Neuronogenesis Predicts Ethanol-Induced Neocortical Neuron Number Deficits
Authors: Gohlke J.M. , Griffith W.C. , Bartell S.M. , Lewandowski T.A. , Faustman E.M.
Published: April 2003

We have developed a computational model that allows for the evaluation of normal and perturbed neurodevelopmental processes. This mathematical construct is used to test the hypothesis that reduced neuronal production is the critical mechanism behind fetal alcohol syndrome. Model predictions of normal neurodevelopment match independent stereological measures but challenge estimates generated using a previously published model of normal neocortical neuronogenesis. Evaluation of data showing an increased cell cycle length after prenatal exposure to ethanol during neocortical neuronogenesis yields predictions of cellular deficits that can account for the permanent neocortical neuronal loss seen in rodents exposed to ethanol concentrations of public health relevance.
Ganglioside Patterns Mature at Different Rates in Functionally Related Subregions of the Rat Pons
Authors: Byers Donna M. , Irwin Louis N. , Cabeza Rafael
Published: April 2003

Gangliosides are known to be developmentally regulated and regionally variable, but these variations have not been shown to occur among precisely defined nuclei of the brain in relation to either aging or function. We have sought to correlate changes in ganglioside distribution with age-related changes in highly specific brain regions known to control a common function, the regulation of rapid eye movement sleep architecture. Gangliosides were extracted and quantified from micropunched regions of the locus coeruleus, dorsal raphe, laterodorsal tegmentum, pedunculopontine tegmentum and the general region of the pons containing these nuclei in young adult (3 months), adult (12 months), and aged (24 months) rats. The ganglioside distribution patterns were generally characteristic of the pons as a whole, but showed a high level of differentiation in time course at specific anatomical sites.