bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic Organophosphate Poisoning following the Percutaneous Injection of Insecticide
Authors: Hadimioglu Necmiye , Dosemeci Levent , Arici Gulbin , Ramazanoglu Atilla
Published: April 2003

Organophosphates are the most common group of chemicals in the southern part of Turkey. Although organophosphate poisoning (OPP) may occur due to skin exposure or inhalation, severe poisoning is usually the result of ingestion to attempt suicide. Despite the fact that there have been a lot of experimental studies using intravenous or percutaneous injection of organophosphates, reports of human poisoning due to percutaneous injection are rare. The systemic signs of OPP have not been described in these reported patients. We report 2 cases having systemic signs of OPP due to percutaneous injection. In our first case, we noticed a 17-day muscle weakness and a 12-day muscarinic syndrome, which required prolonged atropinization. In the second patient, atropine infusion had to be continued for 2 days. Both cases also had severe swelling of the affected limb and wound infection. In conclusion, in cases of percutaneous injection of organophosphates systemic toxicity may develop in addition to local findings such as necrosis and abscesses. Close observation for evidence of systemic involvement is required, and the patient should be carefully monitored for secondary abscess formation and any delayed impairment of neurologic function.
Incidence of Infectious Morbidity and Mortality in Dialysis Patients
Authors: Vanholder R. , van Biesen W.
Published: April 2003

Infections remain among the major causes of disease, hospitalization and death in uremic patients, especially in those treated by dialysis. Several pathophysiologic factors enhance this infectious risk: (1) breakdown of protective barriers; (2) affinity of bacteria for foreign materials; (3) bioincompatibility; (4) uremic toxin retention; (5) deficiency and resistance to vitamin D; (6) carriership of germs, and (7) malnutrition. Twenty to 30% of dialysis patients develop infection, and 20–30% of these die from their infection. Sepsis is significantly more frequent, and mortality secondary to sepsis is 50 times higher than in the normal population. Bacteremia (prevalence 1 episode/100 patient-months) is mainly caused by Gram-positive species, especially in vascular access-related infection and infection of unknown origin. Among these Gram-positive germs, staphylococci play a predominant role. The most frequent and most morbid viral infections are associated with hepatitis. Whereas the incidence of hepatitis B decreases, hepatitis C has become the major variant. The incidence of tuberculosis has increased up to 15 times, and in the Western world it mainly affects patients who immigrated from endemic areas. Fungal infections are also frequent, especially in the setting of peritoneal dialysis. In conclusion, infections remain a frequent and morbid problem in dialysis patients. Preventive measures should be applied more vigorously.
Evolution of Cerebellum-Like Structures
Authors: Bell Curtis C.
Published: April 2003

All vertebrate brains have a cerebellum, and most of them have one or more additional structures that are histologically similar to the cerebellum. The cerebellum-like structures include the medial octavolateral nucleus in most aquatic vertebrates; the dorsal octavolateral nucleus in many aquatic vertebrates with an electrosensory system; the marginal layer of the optic tectum in ray-finned fishes; electrosensory lobes in the few groups of advanced bony fish with an electrosensory system; the rostrolateral nucleus of the thalamus in a few widely scattered groups of bony fish; and the dorsal cochlear nucleus in all mammals except monotremes. All of these structures receive topographically organized sensory input in their deep layers. Purkinje-like cells receive the sensory input near their cell bodies. These cells extend apical dendrites up into the molecular layer where they receive synaptic input from parallel fibers. The cerebellum itself can be included within this characterization by considering the climbing fiber as at least in part a conveyor of sensory information and by recalling that climbing fibers in more basal vertebrates terminate on smooth dendrites close to the soma. Physiological findings from three different systems suggest the hypothesis that cerebellum-like structures remove predictable features from the sensory inflow. Phylogenetic homology can explain the similarities across different taxa for some types of cerebellum-like structures, but similarities within other types cannot be explained in this way. Moreover, phylogenetic homology cannot explain the similarities among different types of cerebellum-like structures. Evolutionary convergence provides the best explanation for all these similarities that cannot be explained by homology. The convergence is almost surely constrained by the availability of a genetic-developmental program for creating cerebellum-like circuitry and by the need within many different systems for the type of information processing that cerebellum-like circuitry can provide.
Antioxidant Enzyme Activities and Malondialdehyde Levels in Patients with Obsessive-Compulsive Disorder
Authors: Kuloglu Murat , Atmaca Murad , Tezcan Ertan , Gecici Ömer , Tunckol Hikmet , Ustundag Bilal
Published: April 2003

To examine the importance of free radicals in the pathogenesis of obsessive-compulsive disorder (OCD), we aimed to evaluate whether malondialdehyde (MDA), a product of lipid peroxidation, and antioxidant enzyme [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)] activity levels were associated with OCD. The patients were divided into two subgroups according to whether DSM-IV major depressive disorder (MDD) was accompanied (OCD + MDD) or not (OCD – MDD). The MDA and antioxidant enzyme levels both in patients and controls were determined. SOD activity levels were significantly higher in the OCD + MDD group compared with the control and the OCD – MDD group. Although the OCD – MDD group had slightly higher SOD activity levels as compared with the controls, the difference was not statistically significant. GSH-Px activity levels were statistically significantly higher in both groups compared with controls. Likewise, there was a significant difference in GSH-Px activity levels between the OCD + MDD and OCD – MDD group. CAT activity levels were slightly higher in the OCD + MDD group compared with the OCD – MDD and control group. MDA levels in both groups were significantly higher than in controls. In addition, the difference in MDA levels between both groups was statistically significant. In conclusion, our results suggest that OCD is associated with free radicals and that it may be a heterogeneous subtype including some biological indications of anxiety and affective disorders. More comprehensive and detailed studies are needed to decipher the exact role of free radicals in OCD.
Incidence of Pre- and Poststroke Dementia: Cracow Stroke Registry
Authors: Klimkowicz Aleksandra , Dziedzic Tomasz , Slowik Agnieszka , Szczudlik Andrzej
Published: April 2003

Background and Purpose: Dementia after stroke may be caused by vascular lesion, but preexisting degenerative changes can also influence its development. After stroke, the patients with coexisting Alzheimer-type pathology need appropriate treatment. The aim of the study was to evaluate the frequency of prestroke and new- onset dementia in stroke patients. Methods: We evaluated prestroke dementia in 250 patients with ischemic or hemorrhagic stroke using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Poststroke dementia was assessed in 220 patients 3 months after stroke by means of the neuropsychological tests and/or IQCODE. The DSM-IV definition of dementia was used. Results: Dementia after stroke was found in 31.4% of stroke patients. Twelve percent of stroke patients had a significant impairment of cognitive functions detected by the IQCODE on admission suggesting prestroke dementia. When we excluded the patients with recurrent stroke, the incidence of pre- and poststroke dementia was 9.3 and 21.2%, respectively. Conclusion: About one tenth of stroke patients have preexisting dementia.
Nitric Oxide Production and Plasma Cyclic Guanosine Monophosphate in Premature Infants with Respiratory Distress Syndrome
Authors: Krediet Tannette G. , Valk Leonieke , Hempenius Ingrid , Egberts Johannes , van Bel Frank
Published: April 2003

A low blood pressure is common in preterm infants with respiratory distress syndrome (RDS). A diminished vascular resistance appears to be an important cause. The endogenous production of nitric oxide (NO), a mediator of vascular smooth muscle relaxation, has been shown to be higher in infants with RDS than in those without. Infants with persistent pulmonary hypertension showed decreased endogenous NO levels as compared with controls. Severe RDS in preterm infants may be accompanied by persistent pulmonary hypertension. To elucidate the role of NO in RDS and low blood pressure, we determined the endogenous NO production in infants with and without RDS by measuring urinary nitrite and nitrate excretions and plasma cGMP levels. In consecutively admitted preterm infants (gestational age <32 weeks), urine samples for measurement of NO2 and NO3 and plasma samples for the determination of the cGMP concentrations were serially collected during the 1st week of life. Arterial blood pressure, therapy to support blood pressure, and additional relevant clinical data were registered simultaneously. 27 infants with and 39 without RDS were included. The urinary NOx levels increased in all patients and were not different between both groups. The plasma cGMP concentrations were higher in the RDS group on days 2, 3, 4, and 7 (p < 0.05). The severity of RDS was positively correlated with plasma cGMP (r = 0.50, p = 0.0001). Although the arterial blood pressure did not differ between the groups, more blood pressure support was needed in the RDS infants during the first 4 days (p < 0.05). A positive correlation was found between blood pressure support and plasma cGMP (r = 0.34, p < 0.0001). The endogenous NO production was not different in infants with and without RDS. Increased plasma cGMP levels in the RDS infants were associated with the severity of RDS and the intensity of antihypotensive treatment. The origin of cGMP in infants with RDS requires further research.
Treating Preterm Infants at Risk for Chronic Lung Disease with Dexamethasone Leads to an Impaired Quality of General Movements
Authors: Bos Arend F. , Dibiasi Jasmin , Tiessen Ansje H. , Bergman Klasien A.
Published: April 2003

Mortality rates do not decline markedly after postnatal corticosteroid therapy and concern has been raised about its neurological sequelae. We studied 37 preterm infants with Prechtl’s method for the qualitative assessment of general movements before, during and after dexamethasone therapy and found that the quality of general movements was impaired in 9 of 13 initially normal infants (p = 0.004, McNemar test). The quality of fidgety movements at 3 months was abnormal in the majority of the infants and correlated strongly with neurological abnormalities at 2 years (Spearman r = 0.785, p < 0.001). Prechtl’s method may prove useful for the early neurological evaluation of alternative corticosteroid treatment strategies for the treatment of chronic lung disease.
A Vaccine for Nicotine Dependence: Targeting the Drug Rather than the Brain
Authors: Pentel Paul , Malin David
Published: April 2003

Nicotine is the principal addictive component of tobacco. Vaccination of rats against nicotine elicits the production of nicotine-specific antibodies which can bind and sequester nicotine in serum and extracellular fluid, reduce nicotine distribution to brain, and reduce many of nicotine’s physiologic and behavioral effects. Vaccination reduces the distribution to brain of both a single nicotine dose and chronic nicotine infusion at rates approximating cigarette smoking. The passive transfer of nicotine-specific antibodies (from vaccinated rabbits) into rats attenuates numerous actions of nicotine: increases in blood pressure and locomotor activity, the induction of nicotine dependence, the relief of nicotine withdrawal by subsequent nicotine and the stimulus properties that allow rats to discriminate a nicotine from a saline injection. Vaccination of rats against nicotine also reduces nicotine-induced dopamine release in the reward pathway of the brain and the reinstatement of nicotine responding, a model for relapse. Because nicotine vaccines target the drug rather than the brain, and the antibodies themselves do not cross the blood-brain barrier, immunization should circumvent the central nervous system side effects that limit the usable dosage of other medications for tobacco dependence. Nicotine vaccines have not yet been tested in humans. The effects of these vaccines in rats are highly dependent upon the concentration of antibody in serum, and are more often partial than complete. If effective for treating tobacco dependence in humans, vaccination will likely benefit from concurrent use of counseling (as is the case with other medications for smoking cessation) and perhaps from its combination with other medications that act via different mechanisms.
Pleural Interleukin-1β in Differentiating Transudates and Exudates: Comparative Analysis with Other Biochemical Parameters
Authors: Alexandrakis Michael G. , Kyriakou Despina , Alexandraki Rea , Pappa Konstantina A. , Antonakis Nikolaos , Bouros Demosthenes
Published: April 2003

Background: The differential diagnosis of pleural effusion is a frequent clinical problem. The possible role of pleural fluid cytokines in discriminating transudates from exudates has not been studied adequately. Objective: The aim of this study was to evaluate the serum and pleural fluid levels of interleukin-1β (IL-1β) and to compare it with common biochemical parameters such as cholesterol (CHOL), lactate dehydrogenase (LDH), total protein and albumin. Methods: One hundred and six consecutive patients with pleural effusion were studied. IL-1β was measured simultaneously in blood and pleural fluid using a radioimmunoassay. Standard laboratory methods were employed for biochemical parameters. Results: Using ROC analysis, a pleural IL-1β cutoff level 18.16 fmol/ml had a sensitivity of 76.8%, a specificity of 58.3% and a positive predictive value (PPV) 86.3% in the discrimination of transudates vs. all exudates. Serum IL-1β levels were higher in the nonmalignant group but without statistical difference compared with transudate patients. In addition, a significant difference was found between serum IL-1β in the malignant group in comparison with those of the transudate group (p < 0.01), also IL-1β levels were significantly increased in exudate effusion when compared with transudate (p < 0.001, p < 0.05, respectively). CHOL values of ≧65 mg/dl had 92.7% sensitivity, and 100% specificity and PPV for both. Conclusions: The results of this study suggest that although IL-1β could be a marker with relatively good sensitivity and PPV for the differentiation of pleural effusion, the cost and time needed do not support its use as a routine laboratory test.
Variability of Exhaled Hydrogen Peroxide in Stable COPD Patients and Matched Healthy Controls
Authors: van Beurden W.J.C. , Dekhuijzen P.N.R. , Harff G.A. , Smeenk F.W.J.M.
Published: April 2003

Background: Because inflammation induces oxidative stress, exhaled hydrogen peroxide (H2O2), which is a marker of oxidative stress, may be used as a non-invasive marker of airway inflammation in chronic obstructive pulmonary disease (COPD). There are no data on the circadian variability of exhaled H2O2 in COPD patients. Objective: The aim of this study was to investigate the variability of the H2O2 concentration in breath condensate of stable COPD patients and of matched healthy control subjects. Methods: We included 20 patients with stable mild COPD (forced expiratory volume in 1 s ∼70% of predicted) and 20 healthy subjects, matched for age, sex and pack-years, all smokers or ex-smokers. Breath condensate was collected and its H2O2 concentration determined fluorometrically three times on day 0 (9 and 12 a.m., and 3 p.m.) and once on days 1, 2, 3, 8 and 21. Results: The mean H2O2 concentration increased significantly during the day in both the patient and control groups (p = 0.02 and p < 0.01, respectively). Over a longer period up to 21 days, the mean concentration did not change in both groups. There was no significant difference between patients and controls. The mean coefficient of variation over 21 days was 45% in the patient group and 43% in the control group (p = 0.8). Conclusions: The exhaled H2O2 concentration increased significantly during the day in both stable COPD patients and controls. Over a period of 3 weeks, the mean H2O2 concentration did not change and the variability within the subjects was similar in both groups.
High Concentrations of Soluble Fas Ligand in Bronchoalveolar Lavage Fluid of Patients with Pulmonary Sarcoidosis
Authors: Shikuwa Chieko , Kadota Jun-ichi , Mukae Hiroshi , Iwashita Tetsuji , Kaida Hideyuki , Ishii Hiroshi , Ishimatsu Yuji , Kohno Shigeru
Published: April 2003

Background and Objectives: Sarcoidosis is a systematic granulomatous disorder of unknown origin characterized by accumulation of T lymphocytes and macrophages in multiple organs. We postulated that apoptosis through the Fas/Fas ligand (L) system may be associated with regulation of immune reactions characterized by the formation of noncaseous necrotizing granulomas. Soluble (s) FasL is not equivalent to membrane-associated FasL since conversion of membrane-bound FasL to the soluble form is associated with downregulation of cytotoxicity. To examine the involvement of sFasL in lung inflammation, we compared the levels of sFasL in bronchoalveolar lavage (BAL) fluid and serum of patients with pulmonary sarcoidosis to those of healthy subjects. Methods: sFasL was measured in BAL fluid and in serum of 15 patients with active pulmonary sarcoidosis by sandwich ELISA. Results: High concentrations of sFasL were detected in BAL fluid and serum of patients with sarcoidosis but not in normal subjects. There was a significant correlation between the percentage of lymphocytes and sFasL concentrations in BAL fluid (r = 0.585, p < 0.05). Conclusions: Our results suggest that sFasL may be upregulated locally in the lung during the inflammatory process of active pulmonary sarcoidosis.
Active Immunization against Nicotine Suppresses Nicotine-Induced Dopamine Release in the Rat Nucleus accumbens Shell
Authors: de Villiers S.H.L. , Lindblom N. , Kalayanov G. , Gordon S. , Malmerfelt A. , Johansson A.M. , Svensson T.H.
Published: April 2003

Background: Tobacco smoking is the largest preventable cause of morbidity and premature mortality in the world. Although its medical consequences are well documented, 20–50% of the population even in developed countries remain tobacco smokers. The drugs presently used in smoking cessation have limited efficiency and, therefore, there is a need for alternative and improved treatments. One novel approach in this regard may be provided by immunization against nicotine. Objective: The present study in male Wistar rats investigated if active immunization with a novel nicotine immunogen, IP18-KLH, may generate nicotine-selective antibodies and, furthermore, whether this treatment might prevent nicotine from exerting its stimulating effect on the mesolimbic, dopaminergic reward system in the brain. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to determine the titer of nicotine antibodies in plasma after immunization with IP18-KLH in Freund’s adjuvant. Competitive ELISA was used to assess the selectivity of the antibodies. Finally, we used in vivo voltammetry to investigate whether active immunization with IP18-KLH could prevent nicotine-induced dopamine release in the shell of nucleus accumbens (NACshell). Results: The present study shows that active immunization with IP18-KLH generates antibodies that are highly selective for nicotine. Furthermore, immunization with IP18-KLH prevented the nicotine-induced increase in dopamine release in the NACshell, a biochemical correlate to the rewarding properties of nicotine. Conclusions: Active immunization with IP18-KLH prevents a central effect of nicotine that is considered critical for the induction of nicotine dependence. Consequently, active immunization may provide long-term protection against initiation of tobacco dependence, an effect that may prove particularly advantageous in relapse prevention.
Active Immunization against Nicotine Prevents Reinstatement of Nicotine-Seeking Behavior in Rats
Authors: Lindblom N. , de Villiers S.H.L. , Kalayanov G. , Gordon S. , Johansson A.M. , Svensson T.H.
Published: April 2003

Background: The presently available pharmaceutical aids in smoking cessation possess a rather limited effectiveness. Therefore, we have synthesized a series of immunoconjugates that stimulate the induction of antibodies which may bind nicotine in the blood, thereby preventing it from passing the blood-brain barrier. Thus, the reinforcing action of nicotine in the brain, which is the driving force in tobacco smoking, should be abolished. Objective: The present study was undertaken to test this notion in a long-term relapse model in rats, measuring the reinstatement of nicotine-seeking behavior, following active immunization with IP18-KLH, one of our immunoconjugates. Methods: Male Wistar rats were immunized with a nicotine-KLH conjugate (nicotine immunogen) and Freund’s adjuvant after having been trained to meet the criteria of stable nicotine self-administration on a fixed ratio (FR3) schedule. The rats were subsequently extinguished from nicotine self-administration behavior and finally, as extinction was completed, they were exposed to small, priming doses of nicotine, which previously have been shown to reinstate the nicotine-seeking behavior. The antibody titers were measured by ELISA. Results: It was found that rats with high titers (>1:10,000) of antibodies against nicotine, in contrast to those with low/no nicotine selective antibodies, do not reinstate nicotine self-administration behavior when they are exposed to nicotine. Conclusions: Our findings indicate that active immunization against nicotine may effectively abolish the reinforcing action of nicotine in brain, an effect which is critical for relapse in nicotine dependence. These data suggest the potential utility of active immunization in smoking cessation programs.
A Case of Micronodular Pneumocyte Hyperplasia Diagnosed through Lung Biopsy Using Thoracoscopy
Authors: Fujitaka Kazunori , Isobe Takeshi , Oguri Tetsuya , Yamasaki Masahiro , Miyazaki Mitsuru , Kohno Nobuoki , Takeshima Yukio , Inai Kouki
Published: April 2003

We present a case of a 39-year-old woman with sporadic tuberous sclerosis (TSC), whose chest radiograph demonstrated bilateral diffuse nodular shadowing. A transbronchial lung biopsy specimen revealed the possibility of multiple atypical adenomatous hyperplasia (AAH), which had not been reported in TSC. Thoracoscopic lung biopsy was, therefore, performed. The specimens revealed the characteristic histological and immunohistochemical features of micronodular pneumocyte hyperplasia, which has been reported as an extremely rare pulmonary manifestation of TSC. In addition, no evidence of AAH or any other pulmonary involvements of TSC including lymphangioleiomyomatosis were detected in biopsy specimens obtained at thoracoscopy.
A Polymorphism of the Norepinephrine Transporter Gene in Bipolar Disorder and Schizophrenia: Lack of Association
Authors: Leszczyńska-Rodziewicz Anna , Czerski Piotr M. , Kapelski Paweł , Godlewski Sebastian , Dmitrzak-Węglarz Monika , Rybakowski Janusz K. , Hauser Joanna
Published: April 2003

Norepinephrine is one of the neurotransmitters which has been implicated in the pathogenesis of mood disorders and schizophrenia. The norepinephrine transporter (NET) gene may be a candidate gene for the study of the genetics of these disorders. In this study, 198 patients with schizophrenia and 100 patients with bipolar disorder were analysed for a silent mutation 1287 A/G, located in the coding region (exon 9) of the NET gene, to determine the association between this polymorphism of the NET gene and bipolar disorder or schizophrenia. No association was found between the studied polymorphism of the NET gene and either bipolar disorder or schizophrenia.
Differential Role of Reactive Oxygen Species in Chemical Hypoxia-Induced Cell Injury in Opossum Kidney Cells and Rabbit Renal Cortical Slices
Authors: Kim Yong Keun , Lee Sung Keun , Ha Mi Suk , Woo Jae Suk , Jung Jin Sup
Published: April 2003

This study was undertaken to evaluate the role of reactive oxygen species (ROS) and lipid peroxidation in chemical hypoxia in opossum kidney (OK) cells and rabbit renal cortical slices. Chemical hypoxia was induced by incubating cells or slices with antimycin A, an inhibitor of mitochondrial electron transport. Exposure of OK cells to chemical hypoxia resulted in a time-dependent cell death and parallel depletion of intracellular ATP. In OK cells subjected to chemical hypoxia, the generation of ROS was increased, and this was prevented by the H2O2 scavenger catalase, but not by the hydroxyl radical scavenger dimethylthiourea (DMTU). Catalase prevented OK cell death induced by chemical hypoxia, but [Cu, Zn]-superoxide dismutase (SOD) and DMTU were not effective. The iron chelators deferoxamine and phenanthroline prevented chemical hypoxia-induced OK cell death, but the potent antioxidants N,N′-diphenyl-p-phenylenediamine (DPPD) and butylated hydroxyanisole (BHA) showed no beneficial effect. Antimycin A in OK cells increased lipid peroxidation, which was prevented by DPPD and phenanthroline. In rabbit renal cortical slices, antimycin A caused an increase in LDH release and lipid peroxidation, and these effects were prevented by ROS scavengers (SOD, catalase, and DMTU), iron chelator (deferoxamine), and antioxidants (DPPD and BHA). However, in primary cultured rabbit proximal tubular cells the antimycin A-induced cell death was not altered by antioxidants. The extent of ATP depletion was similar in renal cortical slices and primary cultured cells treated with antimycin A. These results indicate that chemical hypoxia-induced cell injury is not directly resulted from lipid peroxidation in OK cells, but this cell injury is mediated by lipid peroxidation in rabbit renal cortical slices. This discrepancy may be due to the difference in cell preparation (freshly prepared tubules and cultured cells).
Actin-Associated Proteins in Ameloblast Differentiation
Authors: Cutroneo G. , Anastasi G. , Donadio N. , Favaloro A. , Micali A. , Nastro Siniscalchi R. , Santoro G. , Trimarchi F.
Published: April 2003

Focal contacts are systems of adherens junctions of the cell-extracellular matrix type, which allow the transfer of fundamental signals from the extracellular matrix to nuclear compartments, capable of regulating adhesion, proliferation, migration and differentiation of cells. Recently, many authors have concentrated their attention on epitheliomesenchymal interactions which guide organogenesis of dental germ, identifying numerous growth and differentiation factors and having the inner enamel epithelial cells of the enamel organ as a target. Given that the two cellular compartments in their tooth germ are separated by a basal membrane and by an extracellular matrix, which touches it, we wanted to evaluate the presence of focal contacts through the identification of talin and vinculin, proteins of the actin-associated protein complex. In this study we utilized the hemimandibles of young Wistar rats and we extracted the related odontogenic tooth organs present at their apical end. Specimens are processed with antibody against vinculin and talin. Results show that these junctional system proteins are present at the apical poles of both cellular compartments suggesting that putative epithelial-mesenchymal interactions, other than marker molecules, may use focal contacts as a system for transmission of signals.
Cutaneous Eccrine Glands of the Foot Pads of the Rock Hyrax (Procavia capensis, Hyracoidea, Mammalia)
Authors: Stumpf P. , Welsch U.
Published: April 2003

In order to find correlations between skin gland morphology and specific ethological features, the cutaneous glands of the foot pads of Procavia capensis were studied by histological and various histochemical methods and by electron microscopy. In the foot pads, abundant specific eccrine skin glands occur, which consist of coiled tubular secretory portions and coiled ducts. The wall of the secretory part is composed of cuboidal glandular cells and myoepithelial cells. Among the glandular cells two types occur: clear and dark cells. Clear cells have numerous mitochondria and form a basal labyrinth, indicating fluid transport. Dark cells, which stain strongly with periodic acid-Schiff, contain a highly developed perinuclear Golgi apparatus, large amounts of rough endoplasmic reticulum and many secretory granules indicating production of glycoproteins. Cytokeratin (CK) 19 was found in secretory compartments and ducts, CK14 only in duct cells. Single cells of the secretory coils and ducts may be stained with antibodies against antimicrobial peptides. Some glandular cells contain proliferating cell nuclear antigen-positive nuclei especially in the ducts indicating an increased cell proliferation. Terminal transferase (TdT)-mediated d-UTP nick-end labeling-positive nuclei can be detected predominantly in the secretory coils and rarely in the transitional portions between ducts and end pieces. We suppose that proliferating cells migrate from the ducts to the secretory coils. The secretory product of the eccrine cutaneous glands seems to improve the traction between the foot pads of these animals and the steep and smooth rock formations among which they live.
N-Tosyl-L-Phenylalanyl-Chloromethyl Ketone Eliminates the Increase in Caspase-3 and Bcl-2 Caused by Brain Injury in the Newborn Rat
Authors: Feng Yangzheng , LeBlanc Michael H.
Published: April 2003

N-Tosyl-L-phenylalanyl-chloromethyl ketone (TPCK) is neuroprotective in rat pups. We measured bcl-2, Bax and caspase-3 to determine the mechanisms. Seven-day-old rats had the right carotid artery ligated and were subjected to 2.5 h of 8% oxygen. Ten mg/kg of PTCK or vehicle was given intraperitoneally 15 min prior to hypoxia. At 24 h after hypoxia the brains were removed. Bcl-2 in the hippocampus increased from 0.149 ± (SE) 0.023 in the shams to 0.289 ± 0.037 with injury and vehicle (p < 0.05 vs. shams), which was reduced to 0.177 ± 0.030 by TPCK ( p < 0.05 vs. vehicle). Bcl-2 in the cortex increased from 0.180 ± 0.037 in the shams to 0.655 ± 0.078 with injury and vehicle (p < 0.01 vs. shams), which was reduced to 0.354 ± 0.035 by TPCK (p < 0.01 vs. vehicle). Bax, measured only in the mitochondrial enriched fraction of the cortex, was unchanged. Caspase-3 activity increased with injury to 245 ± 38% of baseline in the hippocampus (p < 0.01) and to 261 ± 69% in the cortex (p < 0.01). Treatment with TPCK reduced this to 132 ± 16% in the hippocampus (p < 0.01 vs. vehicle) and 140 ± 14% in the cortex (p < 0.05 vs. vehicle). In this experiment TPCK reduces bcl-2 and caspase-3 concentration in animals who have been shown in our previous studies to be protected by TPCK from hypoxic ischemic brain injury. This is consistent with the hypothesis that TPCK produces neuroprotection by blocking the apoptotic cascade between bcl-2 and caspase-3.
Excitatory Amino Acid-Elicited Tonic Convulsions in Mice and N-Methyl-D-Aspartate Receptor Activation: Role of Ca2+ Influx and Involvement of Intracellular Ca2+-Dependent Biochemical Processes
Authors: Akaike Nobuhide , Himori Norio
Published: April 2003

Intravenously administered nimodipine (an L-type Ca2+ antagonist) as well as dizocilpine (an N-methyl-D-aspartate – NMDA – antagonist) showed a wide spectrum of anticonvulsant activity in intracerebroventricular mouse models for excessive activation of excitatory amino acid receptors. The duration of Bay k-8644 (L-type Ca2+ agonist; intracerebroventricular administration) caused seizures was significantly reduced by intravenously administered nimodipine. Intracisternal administration of Bay k-8644 lowered the convulsion threshold of an intracerebroventricular injection of NMDA. Intracisternal administration of ω-conotoxin GVIA (N-type Ca2+ antagonist) only tended to inhibit the NMDA-induced tonic convulsions. Intracisternal administration of staurosporine (a protein kinase C inhibitor) or calmidazolium (a calmodulin antagonist) was effective in inhibiting the NMDA-induced tonic convulsions. Calmidazolium, unlike staurosporine, produced side effects at a dose showing its anticonvulsant activity. From these results, it is suggested that excessive activation of excitatory amino acid receptors results in tonic convulsions by virtue of a massive increase of Ca2+ influx mainly through NMDA receptor channels, and at least in part through L-type Ca2+ channels, and in subsequent activation of protein kinase C and possibly calmodulin.
Vinblastine and Interferon-Gamma Combination with and without 13-Cis Retinoic Acid for Patients with Advanced Renal Cell Carcinoma
Authors: Bacoyiannis C. , Dimopoulos M.A. , Kalofonos H.P. , Nicolaides C. , Aravantinos G. , Bafaloukos D. , Samelis G. , Onyenadum A. , Kiamouris Ch. , Skarlos D. , Pavlidis N. , Triantafillidis A. , Kosmidis P. , on behalf of the Hellenic Cooperative Oncology Group (HeCOG) o
Published: April 2003

Background: The aim of this study is firstly to determine the response rates and toxicity of two regimens containing vinblastine (VBL) in combination with interferon-gamma (IFN-γ) in the treatment of patients with advanced renal cell carcinoma (RCC), and secondly to evaluate the additional efficacy of 13-cis retinoic acid (13-CRA) in RCC. Methods: Twenty-nine patients were included in the first trial (Trial 1) and 40 in the second one (Trial 2). The therapy given in Trial 1 consisted of VBL 0.15 mg/kg i.v. every 2 weeks and IFN-γ 100 µg s.c. 3 times weekly. In Trial 2, the therapy consisted of the same two drugs, in the same doses, plus oral 13-CRA 40 mg/day. Results: In Trial 1 there were 3 (10.3%) patients with complete response, 3 (10.3%) patients with partial response, 8 (27.6%) patients with stable disease and 15 (51.7%) patients with progressive disease. In Trial 2, there was no complete response, however, 3 (7.5%) patients had partial response. Additionally, 15 (37.5%) patients maintained stable disease and 14 (35%) patients had progressive disease. In Trial 1, the median survival was 12.56 months (95% CI, 6.8–18.3, range 0.59–42.49) and the median time to progression was 3.21 months (95% CI, 1.7–4.7, range 0.03–42.49). In Trial 2, the median survival was 9.54 months (95% CI, 5.9–13.1, range 0.43–24.1) and the median time to progression was 3.9 months (95% CI, 0.8–7, range 0.26–24.1). In Trial 1, granulocytopenia grade 3 and 4 appeared in 5 (17.2%) patients and anaemia grade 3 in 1 (3.4%) patient. In Trial 2, there were grade 3 toxicities, as granulocytopenia in 5 (12.5%) patients, anemia in 4 (10.0%) patients, stomatitis in 3 (7.5%) patients, fatigue/malaise in 3 (7.5%) patients and 1 (2.5%) had diarrhea. No toxic deaths occurred in both studies. Conclusion: The use of IFN-γ does not enhance the low response of VBL-based chemotherapy. The additional administration of 13-CRA with the combination of VBL and IFN-γ does not add to the efficacy of this combination in patients with advanced renal cell carcinoma. New active agents are needed to treat patients with this disease.
Active Relaxation of Human Gallbladder Muscle Is Mediated by ATP-Sensitive Potassium Channels
Authors: Bird N.C. , Ahmed R. , Chess-Williams R. , Johnson A.G.
Published: April 2003

Background: Active and significant relaxation of the human gallbladder must be one of the facets of its motility during both the filling and emptying cycle. Conflicting reports about the presence or significance of nitric oxide have been reported in the literature. The aim of this study was to investigate the role of nitric oxide and KATP channels in human gallbladder muscle using isolated strips from human gallbladder. Methods: Full thickness strips were obtained from 56 human gallbladders and suspended under isometric tension in organ baths. The effect of nitric oxide donors and inhibitors on cholecystokinin octapeptide- and carbachol-induced contraction was examined. In separate experiments the effect of the KATP channel activator, cromakalim, and the inhibitor, glibenclamide, were determined. Results: Cromakalim induced a significant relaxation of agonist-induced contraction in human gallbladder in vitro, an effect which was abolished by the KATP channel inhibitor glibenclamide. No evidence of significant nitric oxide involvement in relaxation was observed. Conclusions: This study has demonstrated the presence of KATP channels in human gallbladder for the first time. These are capable of causing significant relaxation in the presence of hormonal and muscarinic agonists and may represent a major pathway for gallbladder relaxation.
Inhibition by Female Sex Steroids of Peristalsis in the Guinea Pig Small Intestine
Authors: Heinemann Akos , Pieber Doris , Holzer Peter
Published: April 2003

Aims: The effects of steroid hormones on propulsive peristalsis in the intestine were investigated in order to compare their adverse effect profile on this clinically most important motor pattern. Methods: Peristalsis in isolated segments of the guinea pig small intestine was triggered by luminal distension and recorded via the peristalsis-associated changes of the intraluminal pressure. Drug effects on muscular activity were investigated in a circular muscle preparation of the ileum. Results: Estradiol and progesterone, but not testosterone, hydrocortisone or cholesterol (each at 3–30 µM), caused a prompt and concentration-related increase in the peristaltic pressure threshold at which propulsive muscle contractions were elicited. Mifepristone (RU-486; 30 µM) did not prevent the inhibitory effect of progesterone, but blocked peristalsis per se. Pharmacological blockade of inhibitory neural pathways with NG-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), naloxone (opioid receptor antagonist), apamin or suramin plus pyridoxal phosphate-6-azophenyl-2′,4′-disulphonic acid (P2 purinoceptor blockers) counteracted the inhibitory effect of submaximally (10 µM), but not maximally (30 µM), effective concentrations of progesterone. Estradiol and progesterone depressed circular muscle contractions evoked by cholecystokinin octapeptide to a larger degree than responses to the tachykinin NK1 receptor agonist GR-73,632. Conclusion: The peristaltic motor inhibition caused by sex steroids at micromolar concentrations arises primarily from a depressant action on intestinal muscle activity and may be particularly relevant for high-dose regimens of mifepristone.
Antiangiogenic Effect of Octreotide Inhibits the Growth of Human Rectal Neuroendocrine Carcinoma
Authors: Koizumi Michihiro , Onda Masahiko , Tanaka Noritake , Seya Tomoko , Yamada Takeshi , Takahashi Yoshiyuki
Published: April 2003

Background: Somatostatin and its analogues have antitumor effects on foregut and midgut neuroendocrine (NE) tumors, but their effect on hindgut NE tumors is unclear. We examined the effect of the somatostatin analogue, octreotide, on human rectal NE carcinoma. Materials and Methods: Expression of somatostatin receptor (sst) on NE carcinoma was examined by immunohistochemical staining. Octreotide was added in cell culture medium in order to investigate antiproliferative effect toward NE carcinoma in vitro. Octreotide was administered for 6 weeks to nude mice xenografted with NE carcinoma. We investigated the effect of octreotide on the tumor histologically. The plasma levels of VEGF and bFGF were measured. Results: The NE carcinoma and endothelial cells expressed sst. Octreotide induced NE carcinoma to apoptosis in vitro and in vivo. Octreotide-treated tumors had a massive necrotic area (62.7 ± 19.3% treated vs. 39.7 ± 20.34% untreated, p < 0.05). Microvessels in the treated tumor were decreased (264.0 ± 48.2/mm2 treated vs. 341.4 ± 56.6/mm2 untreated, p < 0.05). The plasma levels of VEGF and bFGF were reduced by octreotide. Conclusions: Octreotide induces rectal NE carcinoma to apoptosis and inhibits angiogenesis in the tumor. These result in tumor necrosis. Octreotide has an antitumor effect on rectal NE carcinoma.
Fractionated Stereotactic Radiotherapy for Acoustic Neuromas
Authors: Williams Jeffery A.
Published: April 2003

Fractionated stereotactic radiotherapy (FSR) for acoustic neuromas offers both higher tumor dose and potential sparing of the facial and auditory cranial nerve functions. Eighty consecutive patients (45 males and 35 females; age 56.8 ± 1.7 years) received FSR for acoustic neuromas and had a median follow-up of 2.9 years (range 2.3–6.5 years). For FSR, 70 patients had 5 daily fractions of 5 Gy (25 Gy total) and 10 patients had 10 daily fractions of 3 Gy (30 Gy total). Volume decreased by an average of 18%. No tumor increased in size, no patient developed facial weakness, and hearing was preserved.
Functional Magnetic Resonance Imaging for the Evaluation of the Motor System: Primary and Secondary Brain Areas in Different Motor Tasks
Authors: Rotte Michael , Kanowski Martin , Heinze Hans-Jochen
Published: April 2003

Functional magnetic resonance imaging was used to characterize the primary and secondary motor system in subjects performing different motor tasks. Nine right-handed subjects performed simple motor tasks using hand, foot, knee, tongue, lips, eyes and the diaphragm-pelvis. All tasks revealed significant activation in primary and secondary motor areas. In the average across subjects, only the activity in the precentral gyrus was statistically distinctive for each motor task and followed the distribution of the motor homunculus. We consider these results as a possible basis of presurgical planning, extending the currently used procedures over a broader spectrum of motor tasks and brain structures leading to a more precise evaluation of functional areas for intracerebral interventions.
Percutaneous Biopsy through the Foramen ovale: A Case Report
Authors: Berk Caglar , Honey Christopher R.
Published: April 2003

A 59-year-old man presented with an intracranial mass that involved the cavernous sinus. It was biopsied percutaneously through the foramen ovale and the diagnosis of meningioma was established. The literature was reviewed for the employment of similar procedures and the potential benefits of this technique explored.
Disseminated Hydatid Disease Involving Orbit, Spleen, Lung and Liver
Authors: Betharia S.M. , Pushker Neelam , Sharma Vidushi , Avinash Mahindrakar , Kashyap Seema
Published: April 2003

Orbital hydatid disease is rare, even in endemic areas. We present a case of disseminated hydatid disease involving the orbit, spleen, lung and liver in a lady aged 35 years. Based on a typical clinical presentation, presence of eosinophilia, a positive indirect haemagglutination test for hydatid disease and presence of similar disseminated, anechoic cystic masses in the liver, lung, spleen and orbit on imaging studies, the diagnosis of hydatid cyst was seriously considered before surgery. Aspiration of the cyst, followed by cryo-extraction of the cyst wall through transconjunctival route was safely performed. Histopathological examination confirmed the diagnosis. In conclusion, multisystemic involvement of liver, lung and spleen in a case of orbital hydatid cyst has never been reported before. The surgical technique adopted in this case is safe and effective.
Plasma Levels of Endothelin-1 in Retinitis Pigmentosa
Authors: Cellini Mauro , Santiago Luigi , Versura Piera , Caramazza Roberto
Published: April 2003

Retinitis pigmentosa (RP) is an inherited retinal disorder clinically characterized by a pale, waxy optic nerve head, attenuated retinal blood vessels and bone spicule pigment in the retina. Hemodynamic studies have demonstrated that RP is associated with a reduction in the retinal and choroidal blood flow. Retinal hemodynamic impairment is also present in the early stages of RP and various hypotheses have been advanced as to its cause. The authors studied 20 patients, 12 males and 8 females, aged between 26 and 42 years (mean 34.6 years) affected by simplex RP. The twenty patients were divided in two groups according to the degree of sight impairment: group A consisted of 10 patients with a visual acuity of 0.3 ± 0.1, visual field mean defect 18.988 ± 3.419 dB and b-wave electroretinogram amplitude of 13.14 ± 0.308 µV. Group B consisted of 10 patients with a visual acuity of 0.8 ± 0.2, visual field MD 10.523 ± 3.582 dB and b-wave electroretinogram amplitude of 26.000 ± 0.757 µV. An increase in plasma levels of endothelin-1 (ET-1) was found as compared with healthy controls: 1.910 ± 0.617 pg/ml vs. 1.180 ± 0.210 pg/ml (p < 0.021), but there was no statistical difference between group A and B (p < 0.163). It is thought that an increase in ET-1 and retinal oxygen levels in RP could lead to vasoconstriction and a decrease in the retinal blood flow worsening the abiotrophic process.
Orbital Sinus Histiocytosis (Rosai-Dorfman Disease): A Lacrimal Gland Involvement
Authors: Quintyn J.C. , Ranty M.L. , Courville P. , Métayer J. , Retout A.
Published: April 2003

We report the clinical and histopathological features of 2 cases of orbital Rosai-Dorfman disease with lacrimal gland involvement but no lymphadenopathy or cutaneous involvement. The first case was a 7-year-old boy, who was referred to the ophthalmology department with a proptosis in the left eye. The second case involved a 57-year-old African man, who developed oedema of the right upper eyelid over a 4-month period. Ocular involvement in Rosai-Dorfman disease is rare (10%). The diagnosis is histological in combination with immunohistology and is often delicate, especially in extranodal localizations. Histopathologically, normal gland morphology was altered by fibrosis and inflammatory cells. To our knowledge, this is the first report on lacrimal involvement in incomplete, thus uncommon sinus histiocytosis with massive lymphadenopathy.
Malignant Transformation of Optic Disc Melanocytoma? A Clinical Dilemma at Presentation with a Review of the Literature
Authors: Sharma Parul M. , Sangal Kartikeya , Malik Praveen , Mathur M.B.
Published: April 2003

Malignant transformation of optic disc melanocytoma is an uncommon feature, although in the past a few cases have been reported. Though our case, a healthy 30-year-old female, presented with all clinical features of melanocytoma, the triad of moderate visual loss, elevation of the lesion of 5.2 mm and an atypical ultrasonic picture could be an indication of malignant change at presentation. In the event of a moderate visual loss, long-term follow-up with serial fundus photographs and ultrasonic measurements is necessary for further management.