bluuebunny/crossref_metadata_2025 huggingface dataset:
Secondary Prevention of Stroke and the Expanding Role of the Neurologist
Authors: Alberts Mark J.
Published: April 2003

Stroke is the leading cause of adult disability and dependency in western society. Following stroke, the risk of myocardial infarction (MI) is increased by a factor of around 2–3 compared with baseline. Indeed, after the first 30 days, stroke survivors are more likely to die from a cardiac event than from a cerebrovascular event. In patients with atherothrombotic stroke, preventing subsequent manifestations of the underlying disease is therefore an important therapeutic goal. A number of options have been shown to reduce the risk of stroke. Aggressively controlling stroke risk factors, such as hypertension, diabetes and smoking, should provide significant benefit in reducing stroke risk; however, it is difficult to realize the full potential of these approaches in routine clinical practice. A number of classes of medication can reduce the risk of stroke and other vascular events, including antiplatelet agents, anticoagulants, angiotensin-converting enzyme inhibitors and statins. Several antiplatelet agents are approved to reduce the risk of recurrent stroke, although only clopidogrel and acetylsalicylic acid (ASA) are approved for the reduction of both stroke and MI in such patients. In the CAPRIE study, clopidogrel showed a statistically significant relative risk reduction of 8.7% (p = 0.043) compared with ASA for the composite endpoint of ischaemic stroke, MI or vascular death. Evidence from animal studies, ex vivo models in humans, and patients undergoing coronary stent insertion or patients with unstable angina/non-Q-wave MI clearly demonstrates the synergistic antiplatelet effect of using clopidogrel with ASA. In summary, most patients with an ischaemic stroke should be treated with an antiplatelet agent to reduce their risk of recurrent stroke, MI, or vascular death. The use of aggressive antiplatelet therapy has the potential to become a new paradigm for managing patients with vascular disease due to atherothrombosis.
Insights from CURE: Using Clopidogrel on Top of Standard Therapy
Authors: Morais João
Published: April 2003

The principal pathophysiological mechanism in patients with unstable angina pectoris (UAP) and non-Q-wave myocardial infarction (NQMI) is atherothrombosis – the formation of a platelet-rich thrombus at the site of a disrupted or eroded atherosclerotic plaque. Despite standard therapy, which includes intravenous heparin or low-molecular-weight heparin and acetylsalicylic acid (ASA) during the acute phase followed by ASA on a long-term basis, the prognosis for patients remains poor. The efficacy of early and long-term treatment with clopidogrel (clopidogrel bisulphate) on top of standard therapy including ASA has recently been tested in patients with UAP and NQMI. In the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Ischaemic Events) Trial, more than 12,500 patients were randomized, in a double-blind manner, to receive placebo or clopidogrel, given as an initial 300-mg loading dose, followed by a 75-mg daily dose. All patients received a recommended dose of ASA (75–325 mg daily). The mean duration of treatment and follow-up was 9 months (minimum 3 months, maximum 12 months). CURE clearly showed that clopidogrel reduced the risk of a composite of cardiovascular death, stroke and MI, with a relative risk reduction of 20% (95% confidence interval, 72–90%; p < 0.001). The protective effect of clopidogrel was apparent within 2 h of initiation of therapy, and the benefit was consistent at 30 days and after long-term treatment. The benefit of clopidogrel was observed across the spectrum of high- and low-risk patients and was obtained with an acceptable risk of bleeding and no increase in intracranial haemorrhage. Based on data from CURE, the use of clopidogrel on top of standard therapy including ASA can be expected to become the new foundation therapy in patients with UAP and NQMI.
Development-Related Expression of AKAP79 in the Striatal Compartments of the Human Brain
Authors: Ulfig N. , Neudörfer F. , Bohl J.
Published: April 2003

The expression of AKAP79 which tethers regulatory proteins within postsynaptic densities has been studied in the two striatal compartments, i.e. patches and matrix, at different stages of the developing human brain by means of immunohistochemistry. The two striatal compartments exhibit various intensities of diffuse immunolabelling and a different number of immunoreactive nerve cells. From the 14th to 20th gestational week a nearly homogeneous distribution of immunoreactive structures in the two compartments of the striatum is seen. Thereafter, a decrease in immunoreactive structures within the matrix is observed (22nd–25th week, intermediate stage). From the 27th week onwards the patch compartment contains distinctly more immunoreactive puncta and nerve cells. Thus, the patches stand out clearly in the immunopreparations. This distribution pattern does not change during proceeding development. AKAP79-immunoreactive nerve cells closely resemble those constituting the class of medium-sized inhibitory projection neurons that receive the dopaminergic input of the striatum. Literature data suggest that AKAP79 may be functionally attributed to dopaminergic inputs. Accordingly, the patterns of AKAP79 expression can at least in part be correlated with the sequential occurrence of dopaminergic innervation. The mature matrix containing a dopaminergic innervation being as dense as in the patches displays distinctly less AKAP79-immunoreactive neurons and puncta than the patches. This discrepancy might indicate that a subpopulation of matrix neurons may, despite dopaminergic input, not express AKAP79.
Scanning Electron-Microscopic View of the Oral and Basal Epithelial Surfaces of the Rat Soft Palate
Authors: Sakai Hiroatsu , Morino Shinichi , Inoué Takao
Published: April 2003

We studied corresponding structures on the oral and basal surfaces of the oral epithelial layer, focusing on the microanatomy of gustatory papillae. Specimens for scanning electron microscopy were obtained from the rat soft palates and fixed with a mixture of 2% paraformaldehyde and 1% glutaraldehyde. They were first prepared without postfixation and conductive-staining to study the oral surface. After examination, the epithelium was reinforced by additional sputter coating and treated with 6 N NaOH at 60°C to exfoliate the basal epithelial surfaces without any significant artifacts. The papillae, showing circular, elliptical or fusiform protuberances on the oral surface, were classified into two types: types I and II. The type I and type II papillae contained one and two taste pores, respectively. On the basal epithelial surface, the basal portions of the taste buds were associated with concentrically arranged nerve fibers and Schwann cells. Another characteristic finding on the basal epithelial surface was the presence of excretory ducts of minor salivary glands in a close spatial relationship to taste buds. It is suggested that saliva coming out through the duct is mixed with food, thus enabling intimate contact with the taste pores of the papillae.
Morphological Evidence for Secondary Vestibular Afferent Connections to the Dorsal Cochlear Nucleus in the Rabbit
Authors: Bukowska Dorota
Published: April 2003

An analysis of central afferent projections to the dorsal cochlear nucleus (dCo), one of the three target nuclei of the auditory nerve, was made using retrograde axonal tracer, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) in the rabbit. The findings showed that, in addition to its afferents from the brainstem auditory nuclei (they are not described herein), the dCo received sparse bilateral connections from the caudal three quarters of the vestibular nuclear complex (VNC). Following selective iontophoretic injections of WGA-HRP into the dCo, a small number of labelled neurones (from 2 to 28 per case) was found in the rostral and caudal portions of the medial vestibular nucleus and in the inferior vestibular nucleus. These neurones were observed mainly in the lateral regions of the nuclei. No labelling appeared in other nuclei which belonged to the VNC. The secondary vestibulocochlear connections have not been reported before in any species. With the anatomical method used, however, their functional role is difficult to explain. Further study is necessary to identify the type of neurotransmitter as well as the physiological properties of vestibular neurones projecting to the dCo, in terms of their responses to a change of the head position and to sound.
Immunocytochemical Light- and Electron-Microscopic Studies of Growth Hormone, Prolactin and Somatomammotroph Cells in Female Goat
Authors: Vásquez F. , Gómez M.A. , Serrano J. , Bernabé A.
Published: April 2003

We have studied the structural and ultrastructural changes that occur in growth hormone (GH), prolactin (PRL) and somatomammotroph (SMT) cells of female goats of the Murciano-Granadina breed during different physiological stages: prepuberty, anestrus, pregnancy and lactation. Serial sections were stained with double immunolabeling, alkaline phosphatase and avidin-biotin complex for light microscopy, and immunogold labeling was used for electron microscopy. These techniques allowed the identification of GH, PRL and SMT cells, which were evenly distributed throughout the whole pars distalis. PRL cells were the most frequent. Both PRL and GH cells showed morphological changes that may be related to a given physiological stage. These changes include the number of cells and the number and size of the secretory granules. SMT cells were clearly identified by having two types of monohormonal secretory granule showing single labeling, in spite of their similar ultrastructural characteristics to the other adenohypophysary cells. They are found in low percentages (0.6%). We postulate that cell aggregates which look like SMT syncytia may be artifacts caused by interdigitation of PRL and GH cells, and that cells which are normally taken to be SMT cells are not an interconversion stage between monohormonal cells.
Age-Related Morphological Changes in Squamous and Parietomastoid Sutures of Human Cranium
Authors: Saito Koji , Shimizu Yoshinaka , Ooya Kiyoshi
Published: April 2003

Age-related morphological changes in the inner and outer surfaces of the squamous and parietomastoid sutures were examined in 65 skulls (35 male, 30 female) obtained from Japanese subjects 5–90 years of age at the time of death. Dimensions were measured in both the horizontal and sagittal planes. Wavelength analysis was done by three-dimensional construction. Irregularities were evaluated by calculating fractal dimensions. The outer squamous suture showed no significant age-related changes in size, but wavelength increased because of the development of bony interdigitations with aging. The posterior part of the outer squamous suture showed significant age-related increases in both wavelength (p < 0.01, R2 = 0.164) and fractal dimension (p < 0.01, R2 = 0.101) in males. The parietomastoid suture showed significant age-related changes in size (p < 0.05), but not in wavelength or fractal dimension. These distinct morphological changes found on both the inner and outer surfaces of the squamous and parietomastoid sutures suggest that the age-related morphological characteristics of these sutures are affected by extrinsic mechanical forces.
Effect of Interferon-beta-1b on Cognitive Functions in Multiple Sclerosis
Authors: Barak Yoram , Achiron Anat
Published: April 2003

Introduction: Multiple sclerosis (MS) is recognised as a central nervous system disease also affecting cognition. The rate of cognitive dysfunction in MS is in the range of 45–65% and adversely affect the quality of life. Objective: To evaluate the effect of 1 year of treatment with interferon-beta-1b (IFNβ-1b) on cognitive functions in patients suffering from relapsing-remitting MS. Methods: A battery of cognitive tests was used to assess verbal learning, delayed recall, visual learning and recall, complex attention, concentration and verbal fluency at baseline and after 1 year of treatment with IFNβ-1b. A group of 23 relapsing-remitting MS patients matched for neurological disability served as controls. Results: Eighteen of 23 patients treated with IFNβ-1b (74%) completed the study. In the IFNβ-1b-treated group, complex attention, concentration as well as visual learning and recall improved significantly (p = 0.024, p = 0.006 and p = 0.005, respectively), while no deterioration was observed in the other dimensions. In the control group, complex attention, verbal fluency, as well as visual learning and recall deteriorated significantly (p = 0.02, p = 0.004 and p = 0.01, respectively), while no deterioration was observed in the other dimensions. Conclusion: Immunomodulating drugs that reduce the relapse rate and slow the disease progression also inhibit cognitive deterioration in patients with MS.
Thalamic Infarcts in Young Adults: Relationship between Clinical-Topographic Features and Pathogenesis
Authors: Pezzini Alessandro , Del Zotto Elisabetta , Archetti Silvana , Albertini Alberto , Gasparotti Roberto , Magoni Mauro , Vignolo Luigi Amedeo , Padovani Alessandro
Published: April 2003

Background: Most reports on thalamic infarcts have focused on clinicoanatomical correlations while the mechanisms of stroke have rarely been investigated. Moreover, most series have included mainly elderly stroke patients, whereas scarce information is available about the etiology of thalamic infarcts in the young. Objective: To investigate the mechanisms of thalamic infarcts according to vascular territory in a series of young adults. Methods: A sample of 24 consecutive patients with thalamic infarcts were found in an unselected series of 129 patients with cerebral infarction aged 18–45 years. Diagnostic investigation included computed tomography and magnetic resonance imaging scans, ultrasonic scanning of the extracranial and intracranial arteries, conventional angiography and magnetic resonance angiography, transthoracic and transesophageal echocardiography and extensive thrombophilic studies. The affected vascular territory within the thalamus was determined using standard templates. Results: Thalamic infarcts constituted almost one fifth of the ischemic strokes in our series. Ten patients (42%) had infarct in the territory of the thalamogeniculate pedicle (group 1), 10 (42%) in the territory of the paramedian thalamosubthalamic artery (group 2) and 3 (12%) in the territory of the tuberothalamic artery (group 3). In 1 patient (4%), the lesion involved more than one vascular thalamic territory. A significant association between cardioembolism and paramedian infarcts was found when comparing the mechanisms of stroke of group 2 with those of the group including infarcts in other thalamic territories (p = 0.002) and with those of group 1 (p = 0.02). Conclusions: Our findings provide information about the epidemiology of thalamic infarcts in young adults and point to a differential association between the distribution of infarcts in specific vascular territories and the mechanism of stroke.
Loss of Postural Reflexes in Long-Term Occupational Solvent Exposure
Authors: Kuriwaka Rika , Mitsui Takao , Fujiwara Soichiro , Nishida Yoshihiko , Matsumoto Toshio
Published: April 2003

Inhalation of organic solvents has long been known to damage various nervous systems, including cerebellum, brainstem, and pyramidal tract. However, little is known about the damage of the dopaminergic system. We report two patients with occupational long-term solvent exposure who developed postural instability without other features of parkinsonism. The concentration of HVA in CSF was decreased and the retropulsion was dramatically improved after the administration of levodopa. These findings indicate that the nigrostriatal dopaminergic neurons were disturbed by chronic solvent exposure, resulting in the loss of postural reflexes.
New Insights into the Viral Theory of Amyotrophic Lateral Sclerosis: Study on the Possible Role of Kaposi’s Sarcoma-Associated Virus/Human Herpesvirus 8
Authors: Sola Patrizia , Bedin Roberta , Casoni Federica , Barozzi Patrizia , Mandrioli Jessica , Merelli Elisa
Published: April 2003

In the last few years, three new herpesviruses, HHV-6, -7 and -8, have been discovered, which share interesting biological characteristics for a possible role in the development of both neurological and lymphoproliferative diseases. In particular HHV-8, besides being strongly associated with Kaposi’s sarcoma, is related with several lymphoproliferative diseases. More recently, specific viral sequences belonging to HHV-8 have been detected in autoptic brain specimens from multiple sclerosis patients and controls, suggesting that, similarly to HHV-6, this novel herpesvirus is strongly neurotropic. HHV-8 is an unusual herpesvirus in that it is able to produce homologues of several human gene products, resulting in alterations in cell cycle, in apoptosis and cell-mediated immune responses. To verify a possible relationship between HHV-8 and the development of amyotrophic lateral sclerosis (ALS), we investigated the presence of signs of HHV-8 infection, by both nested polymerase chain reaction (nPCR) and indirect immune fluorescence analysis in ALS patients. Both PCR and serological data did not suggest a clear role of this virus in originating ALS. Nevertheless, new insights into the mechanisms by which viruses may interact with the host cell genome and with the human immune system make the viral hypothesis of ALS still worthy of further studies.
Clinical Aspects of the AIDS Dementia Complex in Relation to Histopathological and Immunohistochemical Variables
Authors: Grassi M.P. , Clerici F. , Vago L. , Perin C. , Borella M. , Nebuloni M. , Moroni M. , Mangoni A.
Published: April 2003

To correlate cerebral histopathological and immunohistochemical changes in the neuroclinical features of the AIDS dementia complex (ADC), autopsy results of 28 ADC patients were related, in a retrospective analysis, to scores on a standardised neurological examination performed at neurologic onset. From a histopathological point of view, the cases were classified as follows: 9 cases of HIV leucoencephalopathy (HIVL; diffuse myelin damage and rare microglial nodules), 7 cases of HIV encephalitis (HIVE; several microglial nodules and no myelin damage) and 12 cases of mixed HIVL and HIVE (HIVL-E). The groups differed significantly with respect to symptoms and CD4 count at neurologic onset, survival and neurological impairment. Immunohistochemically, the interstitial component (p24-positive cells scattered singly within the white matter) was significantly more prevalent in HIVL, and the micronodular component (p24-positive cells confined within microglial nodules) in HIVE. Neurological damage was worse in cases with a high prevalence of interstitial component or a low prevalence of micronodular component. HIVE, HIVL and HIVL-E are distinct clinical forms of ADC. Neurological impairment is related to white matter damage.
The Winter Season Affects More Severely the Facial Skin than the Forearm Skin: Comparative Biophysical Studies Conducted in the Same Japanese Females in Later Summer and Winter
Authors: Kikuchi Katsuko , Kobayashi Hiromi , Le Fur Isabelle , Tschachler Erwin , Tagami Hachiro
Published: April 2003

Skin disorders such as atopic dermatitis, psoriasis and senile xerosis show a tendency to exacerbate in winter. We investigated the seasonal influence on the functional parameters of the skin in healthy female volunteers of different age groups. Biophysical noninvasive measurements, including transepidermal water loss (TEWL) as a parameter for the barrier function of the stratum corneum (SC), high-frequency conductance as a parameter for the hydration state of the SC, temperature, color and casual surface lipid levels, were conducted during the later summer and winter months in 39 healthy adult Japanese females ranging in age from 24 to 78 years. The measurements were made on the cheek, the exposed area, and flexor forearm, the semicovered area, in the same climate-controlled chamber. The barrier function of the SC was found to be significantly impaired in winter both on the cheek and flexor forearm. This difference between summer and winter was much larger on the cheek than on the forearm. The hydration state of the SC was significantly lower in winter on the flexor forearm, whereas no such seasonal change was apparent on the cheek where sebum levels did not show any seasonal change. We measured the corneocyte size in 24 out of the 39 subjects to estimate a seasonal change of the turnover rate of the SC. It tended to be smaller only on the exposed cheek skin, suggesting an enhanced turnover of the SC in winter, whereas it was somewhat larger on the semicovered flexor forearm. The skin surface temperature and redness were also significantly higher on the cheek in winter. We think that subclinical inflammation resulted in the enhanced turnover rate of the SC associated with elevated TEWL levels observed on the face in winter. In conclusion, the obtained data suggest that the exposed facial skin becomes more irritable under the influence of the dry and cold environment of winter even in healthy individuals where the barrier function of the SC is relatively poor as compared to the skin of other areas.
Treatment of Rheumatoid Arthritis by TNF-Blocking Agents
Authors: Graninger Winfried , Smolen Josef
Published: April 2003

Chimeric, humanized and fully human monoclonal antibodies directed against tumor necrosis factor-α as well as TNF receptor constructs can be administered relatively safely during long-term use for the treatment of rheumatoid arthritis (RA). Their therapeutic efficacy in patients refractory to treatment with conventional disease-modifying drugs was proven in large clinical trials and their ability to slow the progression of disease was demonstrated radiographically. The insights into the pathophysiology of RA provided by the beneficial effects of blocking proinflammatory cytokines will lead to further drug development for this destructive autoimmune disease.
Gemcitabine as First-Line Therapy in Patients with Metastatic Breast Cancer: A Phase II Trial
Authors: Blackstein M. , Vogel C.L. , Ambinder R. , Cowan J. , Iglesias J. , Melemed A.
Published: April 2003

Objectives: This phase II study was conducted to evaluate the efficacy and safety of gemcitabine in patients with metastatic breast cancer (MBC). Methods: Women with histologically or cytologically confirmed bidimensionally measurable MBC not amendable to curative surgery or radiation were eligible. Prior chemotherapy for metastatic disease was not permitted. Patients received gemcitabine 1,200 mg/m2 on days 1, 8 and 15 for 3 weeks every 28 days for a maximum of 8 cycles. Results: Thirty-nine patients, with a median age of 58 years, were enrolled. The overall response rate for the 35 evaluable patients was 37.1% (95% confidence interval [CI], 21.5–55.1%), with 2 complete responses and 11 partial responses. Median time to progression and survival were 5.1 months (95% CI, 3.5–8.8 months) and 21.1 months (95% CI, 11.0–26.9 months), respectively. Chemotherapy was well tolerated, with a median of 4 cycles completed. Grade 4 toxicities were 1 infection and 1 abnormal pulmonary function. Grade 3 neutropenia and thrombocytopenia occurred in 30.3% and 6.3% of patients, respectively. The most common grade 3 non-hematologic toxicity was nausea/vomiting (10.3%). Five of 21 patients had improved Karnofsky performance status (KPS) scores. Conclusion: Single-agent gemcitabine is active and well tolerated as first-line treatment in patients with MBC.
Oedematous Corneal Response of the Fellow Control Eye to Lotrafilcon A and Vifilcon A Hydrogel Contact Lenses in the Rabbit
Authors: Guzey Mustafa , Satici Ahmet , Kilic Adil , Karadede Sezin
Published: April 2003

Purpose: To compare central corneal swelling after 24 h in eyes wearing Lotrafilcon A (high Dk silicone hydrogel) and Vifilcon A (low Dk hydrogel) lenses and the fellow control eyes of rabbits. Methods: 24 New Zealand albino rabbits, free of corneal and conjunctival disease, were anaesthetised with ketamine and xylazin. In 12 rabbits, the right eye was fit with the high Dk Lotrafilcon A silicone hydrogel lens. In the other 12 rabbits, the right eye was fit with the low Dk Vifilcon A hydrogel lens, whereas the left eyes were kept as control eyes. Thereafter, the lens-fitted eyes had partial tarsorrhaphy that left a central gap of approximately 4 mm in length. After 24 h the eyelids were opened and the lenses removed. Central corneal thickness was measured using an ultrasonic pachymeter (Mentor O&O-Advent). Results: Central corneal oedema induced by Vifilcon A lens was significantly higher than that with the Lotrafilcon A lens (p < 0.0001). The oedema of the fellow eyes paired with the Vifilcon A lens-wearing eyes was also higher than that of the fellow eyes paired with the Lotrafilcon A lens-wearing eyes (p < 0.01). Conclusions: The Lotrafilcon A lens induced significantly less corneal oedema than the Vifilcon A lens. Corneal oedema of the fellow eyes appears to be influenced by the swelling of the contralateral lens-wearing eyes. The oedema of the fellow control eye was significantly lower when there was less oedema in the contralateral eye wearing a high Dk silicone hydrogel lens. This may be a sympathetic physiological response. The presence of silicone in the high Dk hydrogel lens may suppress corneal oedema in the lens-wearing eye, thus affecting the fellow eye.
Observational Multicentric Trial Performed with Doxazosin: Evaluation of Sexual Effects on Patients with Diagnosed Benign Prostatic Hyperplasia
Authors: De Rose Aldo Franco , Carmignani Giorgio , Corbu Carlo , Giglio Matteo , Traverso Paolo , Naselli Angelo , Belgrano Emanuele , Catuogno Costanzo , Fontana Dario , Maver Armando , Mirone Vincenzo , Muzzonigro Giovanni , Di Trapani Daniele , Bonini Fabio
Published: April 2003

Introduction: The aim of our study is to verify the effects of doxazosin on sexual function in patients with benign prostatic hyperplasia (BPH). Materials and Methods: We enrolled 102 patients with BPH, selected by nine Italian Urology Departments. Patients were evaluated with the International Prostatic Symptom Score (I-PSS) and divided into two groups: those with intact sexual activity and those with erectile dysfunction. According to the International Index of Erectile Function (IIEF), the second cohort was divided into three subgroups on the basis of the degree of erectile dysfunction degree (severe, moderate or mild). All patients underwent 3 months of therapy with doxazosin. The effects of doxazosin on sexual activity and on voiding symptoms were monitored at 1, 2 and 3 months with IIEF and I-PSS scales. Results: Eighty-six of the 102 initial patients (84%) were monitored until follow-up was completed. The follow-up at 1 month showed a significant decrease in the I-PSS (p < 0.0001) from 20.2 ± 2.01 (base visit) to 13.1 ± 2.21. The mean IIEF was 19.24 ± 6.59 at baseline and 1 month later the score reached 21.44 ± 5.40, thus showing a statistically significant increase (p = 0.0177). This is more evident in the group presenting with severe to moderate erectile dysfunction. I-PSS and IIEF do not significantly change at the 2- and 3-month follow-ups. Conclusions: The use of doxazosin improved sexual function in patients with BPH.
Relation between Volume of Residual Urine and Urodynamic Findings in Women with Cystourethrocele
Authors: Vecchioli Scaldazza Carlo
Published: April 2003

Objective: To evaluate the relation between post-voiding residual urine (PVR) and urodynamic findings, voiding patterns, and the degree of prolapse in women with cystourethrocele. Patients and Methods: According to the average PVR value measured by means of catheterization after three separate and spontaneous micturitions, 73 women with minimal urethral hypermobility (n = 8) or colpocystocele (n = 65) were subdivided into 3 groups: group 1 = patients with a PVR of ≤50 ml; group 2 = patients with a PVR of >50 ml and ≤150 ml, and group 3 = patients with a PVR of >150 ml and ≤500 ml. The patients underwent a thorough physical examination, and prolapse was evaluated and graded. The women then underwent a complete urodynamic investigation. The 3 groups of patients were statistically correlated according to the urodynamic findings, voiding patterns and degree of prolapse. Results: A large PVR in women with cystourethrocele was often associated with poor maximum flow rate, intermittent flow and with the highest degree of prolapse. Conclusion: The present study suggests that uroflowmetry is a very simple, noninvasive, but also essential method of investigation in evaluating female patients with cystourethrocele, particularly when a large PVR is suspected.
Activity of Moxifloxacin and Twelve Other Antimicrobial Agents against 216 Clinical Isolates of Streptococcus pneumoniae
Authors: Esposito Silvano , Noviello Silvana , Ianniello Filomena
Published: April 2003

Background: An increased incidence of macrolide resistance in penicillin-resistant Streptococcus pneumoniae has been described. Methods: With this in mind, 216 S. pneumoniae isolates were evaluated for their in vitro susceptibility to a new fluoroquinolone, moxifloxacin, which was compared with penicillin, amoxicillin, cefuroxime, cefotaxime, ceftriaxone, erythromycin, clarithromycin, ciprofloxacin, sparfloxacin, ofloxacin, vancomycin and teicoplanin. A broth microdilution assay was performed in cation- adjusted Mueller-Hinton broth with 5% (v/v) lysed horse blood according to NCCLS guidelines. Results: Erythromycin resistance was observed in all the 22 penicillin-resistant S. pneumoniae (10.1%). All the penicillin- susceptible S. pneumoniae were susceptible to cephalosporins, whereas all the penicillin-resistant ones showed resistance to cefuroxime and only intermediate susceptibility to cefotaxime and ceftriaxone. The 216 tested strains were inhibited by sparfloxacin and moxifloxacin at concentrations of 0.12–0.5 mg/l and 0.06–0.25 mg/l, respectively, regardlesss of whether the strain was penicillin and/or erythromycin resistant. Seven penicillin-resistant strains displayed resistance to ofloxacin. All isolates were susceptible to vancomycin; teicoplanin MIC values ranged from 0.03 to 0.12 mg/l. The excellent in vitro activity of moxifloxacin against S. pneumoniae was not affected by penicillin and/or macrolides. Conclusion: Moxifloxacin appears to be a promising choice for the treatment of pneumococcal infections, including situations where therapeutic choices are limited due to penicillin and macrolide resistance.
Differences between Two New Quinolones (Gemifloxacin and Trovafloxacin) and Ciprofloxacin in Their Concentration-Dependent Killing of Streptococcus pneumoniae
Authors: Joyanes P. , Pascual A. , Giménez M.J. , García I. , Aguilar L. , Perea E.
Published: April 2003

Background: Ciprofloxacin resistance influences the in vitro effect of new quinolones on Streptococcus pneumoniae.Methods: The early (over 3 h) in vitro bactericidal activity of gemifloxacin, trovafloxacin and ciprofloxacin was explored by time-kill tests against two ciprofloxacin-susceptible (MIC = 0.5 and 1 µg/ml) and two ciprofloxacin-resistant (MIC = 16 µg/ml) S. pneumoniae strains. Results: At subinhibitory concentrations (0.5 × MIC) and inhibitory concentrations (1 × MIC), only gemifloxacin exhibited significant bactericidal activity with, respectively, approximately 85 and approximately 95% decrease in the initial inoculum of the two ciprofloxacin-resistant strains. At concentrations similar to peak serum concentrations (1.5, 3 and 2.5 µg/ml for gemifloxacin, trovafloxacin and ciprofloxacin, respectively) after standard doses, only gemifloxacin exhibited an approximately 99.9% (3 log10) reduction in the initial inoculum for the four strains tested, regardless of their susceptibility to ciprofloxacin. No bactericidal activity was exhibited for the other two quinolones against the ciprofloxacin-resistant strains. Conclusions: Gemifloxacin offers high early bactericidal activity at concentrations similar to peak and trough levels, theoretically preventing regrowth over the dosing interval, and thus dealing with the problem of ciprofloxacin resistance in S. pneumoniae.
HLODs, Trait Models, and Ascertainment: Implications of Admixture for Parameter Estimation and Linkage Detection
Authors: Vieland Veronica J. , Logue Mark
Published: April 2003

Maximizing the homogeneity lod is known to be an appropriate procedure for estimating parameters of the trait model in an approximately ‘ascertainment assumption free’ (AAF) manner. We have investigated whether this same property also holds for the heterogeneity lod (HLOD). We show that, when the genetic models at linked and unlinked loci differ, HLODs are not AAF, and maximizing the HLOD yields parameter estimates that are for all practical purposes meaningless; indeed, the admixture parameter α does not even measure the proportion of linked families within the sample, as is commonly supposed. In spite of this, our results confirm a large body of evidence supporting the use of HLODs as robust tools for linkage detection, and suggest further that maximizing the HLOD over both α and parameters of the trait model can improve accuracy in estimation of the recombination fraction Θ. These findings have important implications for the optimal handling of nuisance parameters in linkage analysis, particularly when evaluating the evidence for or against linkage based on multiple independent heterogeneous sets of data.
The Hopkins Verbal Learning Test and Screening for Dementia
Authors: Hogervorst Eva , Combrinck Marc , Lapuerta Pablo , Rue Judith , Swales Kate , Budge Marc
Published: April 2003

The present study investigated the sensitivity and specificity of the Hopkins Verbal Learning Test (HVLT) for demented patients (n = 82, using NINCDS criteria) and 114 healthy controls – equivalent in age, years of education and gender-ratio – from the Oxford Project to Investigate Memory and Ageing. The HVLT ‘Total Recall’ score had 87% sensitivity and 98% specificity for dementia using a cut-off score of 14.5. Using a ‘Memory’ score (the sum of the ‘Total Recall’ and the ‘Discrimination Index’) with a cut-off score of 24.5 gave a 91% sensitivity and 98% specificity for Alzheimer’s disease cases when compared to controls. Unlike the MMSE, the HVLT has no ceiling effects and does not have to be adjusted for education. We conclude that the HVLT is an easy to administer, quick and well tolerated tool for the screening of dementia.
Corticobasal Degeneration and Frontotemporal Dementia Presentations in a Kindred with Nonspecific Histopathology
Authors: Boeve B.F. , Maraganore D.M. , Parisi J.E. , Ivnik R.J. , Westmoreland B.F. , Dickson D.W. , Hutton M. , Hardy J. , Caselli R.J. , Petersen R.C.
Published: April 2003

We report the clinical, neuropsychological, electroencephalographic and radiologic findings in a kindred with varying clinical presentations of a neurodegenerative disorder. Postmortem examination of one member with clinically suspected corticobasal degeneration (CBD) revealed nonspecific histopathology maximally involving the frontoparietal cortex with negligible degenerative changes in the basal ganglia and substantia nigra. The findings in this and other kindreds demonstrate that (1) similar findings on ancillary testing can occur in relatives presumably suffering from the same pathophysiologic process despite dissimilar clinical presentations, (2) the ‘CBD syndrome’ is not specific for CBD, (3) extrapyramidal dysfunction can exist in the absence of appreciable basal ganglia and nigral degeneration, (4) nonspecific histopathology can underlie familial focal/asymmetric cortical degeneration syndromes and (5) many of the findings in CBD are comparable to those reported in frontotemporal dementia.
Contributions of Other Brain Pathologies in Dementia with Lewy Bodies
Authors: Londos E. , Passant U. , Risberg J. , Gustafson L. , Brun A.
Published: April 2003

The clinical picture with its pathological correlate was analysed in 16 patients fulfilling consensus criteria for dementia with Lewy bodies (DLB). The cases were part of a larger cohort (n = 200) of patients within a prospective longitudinal study of dementing disorders. Six cases exhibited not only Lewy bodies (LBs) but also other brain pathologies such as Alzheimer changes, multiple infarcts or complete and incomplete white matter infarcts. Degeneration of the nucleus basalis of Meynert and substantia nigra was also seen. The 10 cases without LBs all had Alzheimer changes. In 7 cases, these changes were combined with mainly incomplete frontal white matter infarcts. However, the degeneration of brain stem nuclei was less pronounced in these cases. Symptoms such as fluctuations in cognition, falls and episodic confusion appeared in association with arterial hypotension, which developed during the course of dementia in almost all the 16 cases. The majority of the cases were treated with neuroleptics and other potentially hypotensive medication. This study shows that multiple and different pathological features may contribute to a clinical symptom constellation as in DLB. The case study approach reveals the complexity of the clinico-pathological relationships in dementia that might otherwise be lost in the analysis of larger group data.
Establishing a Gradient of Risk in Patients with Acute Coronary Syndromes Using Troponin I Measurements
Authors: Al-Harbi Khalid , Suresh C.G. , Zubaid Mohammad , Akanji Abayomi O.
Published: April 2003

Objective: To evaluate the role of serum troponin I (TnI) estimations in the early risk stratification of patients with acute coronary syndromes (ACS) subsequently diagnosed as acute myocardial infarction (AMI) or unstable angina (UA). Subjects and Methods: Blood samples were collected from 86 patients admitted to the Coronary Care Unit of the Mubarak Al-Kabeer Hospital, Kuwait, with a diagnosis of ACS on admission (TnI-1) and after 8 h (TnI-2) and 16 h (TnI-3). Blood was also collected from 38 age-matched healthy controls for comparison. Serum TnI was measured by paramagnetic particle chemiluminescent immunoassay. Results: Serum TnI of <0.05 ng/ml, corresponding to the 99th percentile, was established for healthy subjects. Patients diagnosed as UA had a 99th percentile TnI-1 value of about 0.30 ng/ml. The best specificity and sensitivity for ACS was obtained for TnI-2; indeed, TnI-2 >0.3 ng/ml gave a >80% certainty of diagnosis of AMI. Also, TnI-2 <0.3 ng/ml in ACS patients was approximately 80% sensitive for the diagnosis of UA but relatively nonspecific (approximately 40%). Specificity for TnI-2 for the diagnosis of UA improved to about 90% by narrowing the diagnostic range to 0.05–0.3 ng/ ml. TnI values in UA increased by <100% at 8 h, while in AMI, this increase was up to 1,000%. Conclusion: In the evaluation of ACS, admission and 8-hour serum TnI <0.05 ng/ml is probably not cardiac in origin; serum TnI >0.3 ng/ml on admission and increasing rapidly by 8 h is likely AMI, and serum TnI >0.05 and <0.3 ng/ml on admission with a mild increase by 8 h is likely due to UA.
Hospital-Acquired Clostridium difficile Infection amongst ICU and Burn Patients in Kuwait
Authors: Rotimi V.O. , Mokaddas E.M. , Jamal W.Y. , Verghese T.L. , El-Din K. , Junaid T.A.
Published: April 2003

Objectives: To prospectively study the prevalence of nosocomially acquired Clostridium difficile, a major cause of diarrhoea in hospitalized patients, in the intensive care units (ICUs) and burn unit (BUs) of three teaching hospitals in Kuwait. Methods: During a 1-year prospective study, stool/rectal swabs were obtained from 344 patients admitted into the ICUs of Mubarak Hospital (ICU-1), the Kuwait Cancer Control Centre (ICU-2), and the BU of Ibn Sina Hospital. The presence of C. difficile and/or its toxin was detected by serially culturing the specimens on differential, selective and enriched media and the use of TOX-A/B test, on admission and at subsequent 1-weekly interval until discharge. Results: Out of the 344 patients admitted into these units, over a study period of 1 year, only 263 (77%) were evaluable. All of them had negative stool culture/toxin on admission. Overall, 25 (9.5%) of these 263 patients acquired C. difficile during their hospitalization. Thirteen (7%) of 187 patients acquired C. difficile in ICU-1, 9 (36%) of 25 on ICU-2 and 3 (5.9%) of 51 patients in BU. Eight (32%) developed diarrhoea attributable only to C. difficile and/or toxin, and the remaining 17 (68%) were asymptomatic: none had pseudomembranous colitis. The diarrhoea in these patients was associated with antibiotic use, the main trigger-antibiotics being the third-generation cephalosporins. Acquisition occurred within 4–53 days of admission, with the majority occurring in the first 15 days. Conclusion: Overall, the prevalence of hospital-acquired C. difficile infection/colonization was less than 10%. The use of third-generation cephalosporins was high and was related to the development of diarrhoea. Once acquired, diarrhoea developed in about one third of C. difficile-positive cases, an indication that C. difficile infection/colonization endemic in the hospital ICUs studied is usually transmitted among the hospitalized patients.
Activation of the Inflammatory Response System in Autism
Authors: Croonenberghs Jan , Bosmans Eugene , Deboutte Dirk , Kenis Gunter , Maes Michael
Published: April 2003

Background/Aim: There is now some evidence that autism may be accompanied by abnormalities in the inflammatory response system (IRS). Products of the IRS, such as proinflammatory cytokines, may induce some of the behavioral symptoms of autism, such as social withdrawal, resistance to novelty and sleep disturbances. The main aim of the present study was to examine whether autism is accompanied by an activation of the IRS. Methods: We measured the production of interleukin (IL)-6, IL-10, the IL-1 receptor antagonist (IL-1RA), interferon (IFN)-γ and tumor necrosis factor (TNF)-α by whole blood and the serum concentrations of IL-6, the IL-2 receptor (IL-2R) and IL-1RA. Results: This study showed a significantly increased production of IFN-γ and IL-1RA and a trend toward a significantly increased production of IL-6 and TNF-α by whole blood of autistic children. There were no significant differences in the serum concentrations of IL-6, IL-2R and IL-1RA between autistic and normal children. Conclusions: These results suggest that autism may be accompanied by an activation of the monocytic (increased IL-1RA) and Th-1-like (increased IFN-γ) arm of the IRS. It is hypothesized that increased production of proinflammatory cytokines could play a role in the pathophysiology of autism.
Brain Function and Effects of Shift Work: Implications for Clinical Neuropharmacology
Authors: Garbarino Sergio , Beelke Manolo , Costa Giovanni , Violani Cristiano , Lucidi Fabio , Ferrillo Franco , Sannita Walter G.
Published: April 2003

Night or shift work is to a relevant extent unavoidable, suits a growing preference for flexibility and is predicted to spread. However, a significant percentage of shift workers report discomfort or health problems and they often (15–20% of cases) move to different occupations. Apart from social implications, the issue has medical and scientific relevance, with evidence suggesting that the circadian rhythm phases are neither equivalent nor interchangeable with respect to function and performance. Shift work may affect the gastrointestinal and cardiovascular functions, alter the hormonal and sleepiness cycles, favor sleep disturbances of medical relevance, interfere with behavior and social life and increase the risk of accidents (e.g. road accidents). The implications for clinical (neuro)pharmacology are relevant and, in several instances, critical. Shift work can interfere with mechanisms regulating drug kinetics in peripheral compartments and action at selective brain sites, either directly or through effects on the gastrointestinal/hormonal cycles. In this paper, the relevant literature is reviewed and original data on the effects of shift work are reported. Basic and clinical research should take into account the possible effects on drug action of an active life and working schedule in inappropriate phases of the circadian cycles and the risk of inadequate drug dosing or inexpected abnormal action in subjects under long-term or chronic treatment. A scientific approach, action by the scientific community involved in pharmacological research and monitoring by the regulating agencies are advisable. Regulation may help reduce the medical and social impact and improve quality of life.
NMR Spectroscopic Analysis of Rat Brain Development: In vitro Proton and Carbon Studies of Whole Tissue and Its Phospholipid Fraction
Authors: Zancanaro Carlo , Bolner Andrea , Righetti Claudia
Published: April 2003

The developmental patterns of the rat brain at several postnatal time points were investigated in Folch (chloroform-methanol) extracts. The chloroform- (lipid-containing) and water-soluble (cytosolic) fractions of whole-tissue extracts and the phospholipid fraction separated from the organic fraction by chromatography were analysed by means of high-resolution 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. Analysis of the cytosolic fraction showed the changing patterns of several brain metabolites during postnatal maturation, in full agreement with data obtained from perchloric acid extracts. 1H NMR spectroscopy of the phospholipid fraction allowed for quantitative evaluation of fatty acid acyl chain length, mean unsaturation and mean polyunsaturation. It was found that both mean unsaturation and polyunsaturation are lower in adult brain phospholipids than during the first 3 postnatal weeks. 13C NMR spectroscopy of the same fraction showed that the molar percentage of C18 fatty acids (oleic, linoleic, linolenic) in brain phospholipids is similar at all the investigated time points. These results indicate that the combination of Folch extraction with simple chromatographic procedures and NMR analysis yields useful data to define the chemical maturation of the brain.
Study of the Role of the Low-Affinity Neurotrophin Receptor p75 in Naturally Occurring Cell Death during Development of the Rat Retina
Authors: Ding Jindong , Hu Bing , Tang Louisa S. , Yip Henry K.
Published: April 2003

The aim of this study was to examine the tempo-spatial expression of low-affinity neurotrophin receptor p75, or p75NTR, and its role in the induction of retinal ganglion cell (RGC) apoptosis in the rat retina during development. The cellular distribution of p75 in the retina was demonstrated with immunohistochemistry and double-immunofluorescent staining. Apoptosis in the developing rat retina was detected by DNA gel electrophoresis, and the number of RGCs undergoing apoptosis was estimated by terminal deoxyribonucleotidyl-mediated dUTP-digoxigenin nick end labeling (TUNEL). To localize p75 on apoptotic RGCs, p75 immunofluorescence and TUNEL fluorescent staining was performed on sections with Fluoro-Gold-prelabeled RGCs. p75 immunoreactivities were not detected either on the RGCs or TUNEL-positive cells, whereas Müller cell processes were p75 immunopositive. Thus, it was most unlikely that p75 induced apoptosis of RGCs in the rat retina.