bluuebunny/crossref_metadata_2025 huggingface dataset:
Ischaemic Cerebrovascular Events in HIV Infection
Authors: Evers Stefan , Nabavi Darius , Rahmann Alexandra , Heese Christoph , Reichelt Doris , Husstedt Ingo-W.
Published: April 2003

Several case reports and series described ischaemic cerebrovascular events in HIV infection. However, the exact prevalence and the clinical features of these events are unknown. We performed a cohort study on 772 consecutive HIV infected patients and evaluated the rate of transient ischaemic attacks (TIA) and of completed stroke. A total prevalence of 1.9% for TIA (0.8%) and stroke (1.2%) was calculated resulting in an annual incidence rate of 216 per 100,000. The prevalence was highest in the later stages of the infection. Stroke patients had a poorer immunological state than the TIA and the cohort patients. Probable (n = 3) and possible (n = 2) vasculitis and cardiogenic embolism (n = 2) could be detected as aetiology, the remaining patients had a cryptogenic event. Our data suggest that ischaemic cerebrovascular events are more common in HIV infected patients than in the general population and that a part of these events might be caused by HIV associated vasculitis or vasculopathy.
Fistula Involving Portal Vein and Duodenum at the Site of a Duodenal Ulcer in a Patient after Previous Extrahepatic Bile Duct Resection and Brachytherapy
Authors: Povoski Stephen P. , Shamma’a John M.
Published: April 2003

Fistulas involving the portal venous system and gastrointestinal (GI) tract are rare. However, they can cause life-threatening GI hemorrhage. A case of a fistula between the main portal vein and the posterior wall of the duodenal bulb at the site of a duodenal ulcer in a patient who had previously undergone an extrahepatic bile duct resection and brachytherapy for mucinous cystadenocarcinoma is reported. Consideration should be given to this entity in the differential diagnosis of GI hemorrhage in patients with a history of previous major biliary surgery.
Neuronal Classes in the Isocortex of a Monotreme, the Australian Echidna (Tachyglossus aculeatus)
Authors: Hassiotis M. , Ashwell K.W.S.
Published: April 2003

We have used Valverde-Golgi and Golgi-Colonnier techniques to analyze cortical neuronal morphology in four regions (frontal cortex, primary motor cortex, primary somatosensory cortex, primary visual cortex) of the isocortex of the echidna (Tachyglossus aculeatus). Eight classes of neurons could be identified – pyramidal, spinous bipolar, aspinous bipolar, spinous bitufted, aspinous bitufted, spinous multipolar, aspinous multipolar and neurogliaform. All except the pyramidal neurons were morphologically similar to neuronal classes seen in eutherian and metatherian isocortex. Pyramidal neurons made up a small proportion of all cortical neurons encountered in our preparations of echidna cortex (34% in visual cortex, 35% in somatosensory cortex, 41% in frontal cortex and 49% in motor cortex) compared to both reported values in eutherian cortex and values we found in rat cortex impregnations prepared in an identical fashion to the echidna material (75% in rat motor and 78% in rat somatosensory cortex). Many pyramidal neurons in the echidna isocortex were atypical (30–42% depending on region) with inverted somata, short or branching apical dendrites and/or few basal dendrites, very different from the usual pyramidal neuron morphology in eutherian cortex. Dendritic spine density on apical and basal dendrites of echidna pyramidal neurons in somatosensory cortex and apical dendrites of motor cortex pyramidal neurons was also lower than that found in the rat. The present findings are consistent with both pyramidal neurons and the many diverse types of non-pyramidal neurons having already emerged as discrete morphological entities very early in mammalian cortical evolution, at the time of divergence of the therian and prototherian lineage.
Axial Length Changes Accompanying Successful Nonpenetrating Glaucoma Filtration Surgery
Authors: Üretmen Önder , Ateş Halil , Andaç Kutay , Deli Belgin
Published: April 2003

We aimed to evaluate the effect of nonpenetrating glaucoma filtration surgery on axial length (AL). Thirty patients (30 eyes) who underwent successful nonpenetrating glaucoma filtration surgery were prospectively analyzed. AL was measured preoperatively and postoperatively at 1 and 12 months. Associations between change in AL and age, gender, diagnosis, preoperative and postoperative visual acuity, refraction and intraocular pressure (IOP) were analyzed. AL decreased in 22 of 30 eyes postoperatively. The mean change in AL measurement was –0.15 ± 0.27 mm (range –1.37 to +0.12 mm) at 1 month. Regression analysis showed that young age, a high preoperative IOP and a greater change in IOP were associated with a greater decrease in AL (p < 0.02). The mean AL at 12 months was almost the same as the preoperative value (p >0.2), but was significantly greater than the mean AL 1 month postoperatively (p = 0.001). There was no statistically significant difference between the IOP levels obtained postoperatively at 1 and 12 months (p >0.1). Nonpenetrating glaucoma surgery can result in a small decrease in AL which can reverse during the follow-up period.
Susceptibility of Enamel Surfaces to Demineralization after Application of Fluoridated Carbamide Peroxide Gels
Authors: Attin T. , Kocabiyik M. , Buchalla W. , Hannig C. , Becker K.
Published: April 2003

The aim of the present study was to evaluate the effect of experimental, fluoridated carbamide peroxide gels on formation of erosively induced demineralization of enamel. Seventy-five bovine enamel specimens were polished for microhardness determination and evenly distributed among 5 groups (A–E). The specimens were treated with 10% carbamide peroxide gel (8 h) and subjected twice to remineralization for 2 h in artificial saliva and demineralisation for 90 s in 1% citric acid, pH 2.2. The cycles of treatment with carbamide peroxide and twofold re- and demineralization were repeated three times. The carbamide peroxide gels were different in pH and fluoride content. Gel A (pH 7.0) and gel B (pH 5.7) were fluoridated (0.5% F), gel C (pH 7.0) and gel D (pH 5.7) were not fluoridated. In control group E the samples were not treated with a gel, but stored in 100% humidity for 8 h instead. Knoop microhardness of the specimens was assessed directly after polishing, and after each carbamide peroxide treatment and demineralization. All specimens showed a loss of microhardness at the end of the experiment. After 3 days, the controls revealed a significantly lower hardness loss compared to the specimens treated with the carbamide peroxide gels. Surface softening was significantly lower for the specimens of group A compared to the remaining groups (B–D), which were not significantly different among each other. It is concluded that treatment with either fluoridated or unfluoridated carbamide peroxide gels, at either neutral and acidic pH, renders enamel more susceptible to demineralization. Use of a fluoridated neutral gel decreases the degree of surface softening compared to the other gels investigated.
Influence of Olive Oil Emulsions on Dentin Demineralization in vitro
Authors: Buchalla W. , Attin T. , Roth P. , Hellwig E.
Published: April 2003

The effect of two different concentrations of olive oil emulsions on development of artificial caries-like dentin lesions under severe demineralizing conditions was investigated. Bovine dentin samples (n = 180) were ground flat, polished, divided into four groups, and subjected to three demineralization cycles per day. Samples were stored in one of the following solutions for 5 min prior to demineralization in a buffer solution (pH 5): Group 1: 50% oil emulsion (olive oil and distilled water); group 2: 5% oil emulsion; group 3: distilled water; and group 4: 1,500 ppm sodium fluoride. Daily up to 9 days, lesion depth (ld) and mineral loss (ΔZ) were determined by means of microradiography and analyzed by ANOVA and Tukey’s studentized range test (p ≤ 0.05). Lesion depth increased with time for all groups. Mineral loss increased in groups 1–3. A small but significant decrease in mineral loss was observed following treatment with lipid emulsions as compared to treatment with distilled water, but fluoride treatment was considerably more effective. Mean mineral loss (means ± SD in vol%·µm) averaged over the study period was 4,368 ± 1,599, 4,536 ± 1,823, 4,849 ± 1,798, and 789 ± 177 for group 1, 2, 3, and 4, respectively. Ratio (ΔZ/ld) remained constant around 30 vol% for groups 1–3, but decreased for group 4. In conclusion, externally provided lipids have the potential to reduce dentin demineralization in vitro.
Relationships between a Clinical-Visual Scoring System and Two Histological Techniques: A Laboratory Study on Occlusal and Approximal Carious Lesions
Authors: Kidd E.A.M. , Banerjee A. , Ferrier S. , Longbottom C. , Nugent Z.
Published: April 2003

One aim of the present laboratory study was to determine whether a visual scoring system (ERK) developed for occlusal caries could be applied to approximal lesions. A new histological technique (autofluorescence, AF) recognises dentine that is soft and would be removed with an excavator during operative treatment. A second aim was to investigate the relationship between the visual scoring system (ERK) and AF of dentine both occlusally and approximally. The sample comprised 93 extracted teeth chosen to represent the range of visual scores on approximal and occlusal surfaces. After sectioning through the investigation site, the cut faces were examined in a stereomicroscope and the depth of demineralization was scored. Autofluorescence was viewed with a confocal laser scanning microscope. Results showed reasonable correlation between the visual scores and the stereomicroscope histological evaluations for occlusal surfaces and non-cavitated approximal surfaces. However, cavitated approximal surface lesions were less advanced histologically than cavitated occlusal carious lesions. The AF technique indicated that several lesions with intact surfaces would have had soft, excavatable dentine, whereas several with microcavities would not.
Predicting the Dermal Absorption of Thalidomide and Its Derivatives
Authors: Hadgraft J. , Goosen C. , du Plessis J. , Flynn G.
Published: April 2003

Concern has been expressed about the ability of simple algorithms to predict skin permeability and hence skin flux. For a series of thalidomide analogues, a number of software packages have been used to predict octanol water partition coefficients. These, in conjunction with molecular weight, have then been used to calculate skin permeability coefficients. These compare favourably with experimental values. Some of the software packages also predict aqueous solubilities, which can be subsequently used to calculate maximum skin flux. The predicted and measured solubilities have been compared together with the maximum fluxes. The results show that software can be used to predict octanol water partition coefficients and aqueous solubilities (more accurately if the melting point of the compound is known) and hence to obtain very reasonable estimates of skin permeation parameters. These are useful in predicting which analogue has the most appropriate properties for dermal delivery; in the case of the thalidomide analogues, it is the methyl-substituted compound that is best.
Bifidobacterium-Fermented Soy Milk Extract Stimulates Hyaluronic Acid Production in Human Skin Cells and Hairless Mouse Skin
Authors: Miyazaki K. , Hanamizu T. , Iizuka R. , Chiba K.
Published: April 2003

We examined the effects of Bifidobacterium-fermented (BE) and nonfermented (SME) soy milk extracts on the production of hyaluronic acid (HA) in vitro and in vivo. BE, but not SME, significantly enhanced the production of HA in monolayer and organotypic cultures of human keratinocytes, in cultures of human skin fibroblasts, and in hairless mouse skin following topical application for 2 weeks. In the organotypic cultures formed by a similar structure to human epidermis, BE also extended the distribution of HA. Genistein and daidzein, known to stimulate HA production, were detected in BE at a concentration of 0.18 and 0.07 mM, respectively, but not in SME. Therefore, BE has the potential to enhance HA production in the epidermis and dermis, mainly due to genistein released from its glycoside during fermentation. BE is expected to prevent the age-dependent loss of cutaneous HA.
Prevalence of Caries and Lesions Treatable through the ART Approach in High Caries Risk Schoolchildren in Damascus, Syria
Authors: Taifour Dia , Frencken Jo E. , Beiruti Nabil , van’t Hof Martin A. , Truin Gert-Jan
Published: April 2003

Objective: To determine the prevalence of dentinal lesions treatable through the atraumatic restorative treatment (ART) approach for high caries risk schoolchildren. Subjects and Methods: A convenience sample was taken of 1,542 grade 1 and 931 grade 2 children from 21 primary schools in a low socio-economic area in Damascus. Dentinal lesions in which the smallest excavator (diameter of 0.9 mm) could enter the cavitated lesion were considered treatable using the ART approach. Mann-Whitney U and ANOVA tests were used to analyse the data. Results: The mean dmfs and dmft scores of the 6- to 7-year-olds (grade 1) were 9.0 and 4.4, respectively. The mean DMFS and DMFT scores of the 7- to 8-year-olds (grade 2) were 1.6 and 1.4, respectively. At least 89.9 and 54.9% of the dentinal lesions in the deciduous and permanent dentition that were in need of a restoration, respectively, were diagnosed as treatable using ART. Conclusion: A high proportion of dentinal lesions in need of restorations in both deciduous and permanent dentitions in this high caries risk group of 6- to 8-year-olds were diagnosed as being treatable using the ART approach.
Air Travel-Associated Venous Thromboembolism
Authors: Iqbal Omer , Eklof Bo , Tobu Mahmut , Fareed Jawed
Published: April 2003

Long-distance air travel is increasing and cases of venous thromboembolism (VTE) following air travel have attracted both considerable public attention and legal claims against airlines. VTE is a common disorder worldwide with a notably high incidence in older individuals. Many biochemical factors that lead to, or accentuate, thrombus formation are associated with increased risk of VTE. These factors include thrombophilia, activated protein C resistance and factor V Leiden, prothrombin gene mutation, antiphospholipid antibodies, protein S and protein C deficiencies, and methylene tetrahydrofolate reductase polymorphism and homocysteinemia. Individual physical characteristics including age, weight and height are significant for personal risk of VTE as are other factors such as use of oral contraceptives in women. In the case of air travel-related venous thrombosis, superimposed upon these individual factors are the environmental factors directly related to air travel. Travel-related factors include stasis associated with prolonged periods of immobility, physiological stresses resulting from exposure to the cabin environment (low humidity and hypoxia) in long-haul flight and other in-flight factors. It is suggested that passenger behavior (movement, avoidance of dehydration and of alcohol) and appropriate pharmacological prophylaxis for high-risk travelers can reduce the likelihood of VTE. Physical prophylaxis (use of compression stockings or in-flight exercise devices) may also be of general benefit to passengers. It is recommended that airlines become more proactive in educating passengers concerning the dangers of VTE and in promoting passenger actions that can reduce risk. Airlines should also work to avoid cramped seating conditions (seat size and pitch) that contribute to prolonged immobility. Governments and regulatory authorities should mandate the provision of adequate seating conditions and a good cabin environment and should support studies that will define risks and determine the efficacy of protocols to minimize dangers of VTE. Increased long-haul air traffic and an aging population suggest that travel-related VTE may present a growing healthcare threat and has highlighted a need for additional biomedical research into the causes and potential solutions to this problem.
Diagnostik und Prophylaxe der Cervixinsuffizienz in der Mehrlingsschwangerschaft
Authors: Strauss Alexander , Müller-Egloff Susanne , Heer Ivo Markus , Dannecker Christian , Hepp Hermann
Published: April 2003

Fragestellung: Der Ausprägungsgrad von Frühgeburtlichkeit bestimmt in Mehrlingsgraviditäten massgeblich den Ausgang der Schwangerschaft. Nachdem Cervixinsuffizienz einer der häufigen Auslöser einer vorzeitigen Entbindung bei höhergradigen Mehrlingen ist, kommt ihrer Früherkennung und Prophylaxe hohe Bedeutung zu. Methoden: Mehrlingsschwangerschaften unter volumetrischer Cervixüberwachung bzw. nach prophylaktischer Cerclage konnten mit Kontrollgruppen verglichen werden. Ergebnisse: Die Volumenbestimmung der Cervix uteri gelang bei allen 34 Untersuchungen, auch bei den 6% der Mehrlingsschwangerschaften, bei denen die konventionelle abdominelle Cervixlängenmessung aufgrund einer Obstruktion der Ultraschallebene misslang. Der Gebärmutterhals war durchschnittlich 28,7 mm (SD 7,7) lang. Das mittlere Cervixvolumen betrug 30,0 cm3 (SD 16,0). Ein signifikanter Zusammenhang zwischen Volumen und Länge der Cervix uteri (p = 0,01) ist an der sukzessiven Verminderung beider Parameter im Schwangerschaftsverlauf abzulesen. Eine prophylaktische Cerclage war bei 17% der untersuchten Drillingsmütter im Mittel in der 16. (+2) SSW (98.–138. Tag) und bei 50% der untersuchten Vier- und Fünflingsschwangerschaften in der 15. (+2) SSW (78.–152. Tag) gelegt worden. Das mittlere Zeitintervall zwischen der Operation und der Entbindung betrug für Drillinge 106 Tage (62–119) und für Vier-/Fünflinge 96 Tage (57–142). Die prophylaktisch intendierte Cerclage konnte die Tragzeit nicht verlängern. Ebenso wurde kein positiver Effekt auf die Schwangerschaftsbetreuung (Hospitalisierung, Tokolyse) oder die kindlichen Parameter erreicht. Schlussfolgerungen: Trotz des Versagens einer operativen Frühgeburtsprophylaxe wird durch die frühzeitige, nichtinvasive Diagnostik einer Cervixinsuffizienz die risikoadaptierte Schwangerschaftsbetreuung möglich.
Adrenopause und Dehydroepiandrosteron: Pharmakotherapie versus Substitution
Authors: Römmler Alexander
Published: April 2003

Hintergrund: Die Adrenopause ist als alterstypische partielle Nebennierenrindeninsuffizienz durch erniedrigte Blutspiegel von Dehydroepiandrosteron (DHEA) und DHEA-Sulfat (DS) bei unverändertem Cortisol charakterisiert. Für DHEA sind eigenständige Wirkungen sowie solche als Vorläufer von Sexualhormonen im ZNS und in der Peripherie etabliert. Günstige epidemiologische Daten höherer DS-Spiegel bei Männern sowie positive klinische Berichte über eine DHEA-Substitution bei beiden Geschlechtern lassen seinen Einsatz zur Prävention und Beeinflussung von Alterungserkrankungen als sinnvoll erscheinen. Bisher wurden tägliche orale Einheitsdosierungen von DHEA mit 50–100 mg bei Männern und 25–50 mg bei Frauen eingesetzt, die meist supraphysiologische Blutspiegel bewirken. Patienten und Methode: Wir berichten über Dosisfindungsstudien über 6–12 Wochen bei jeweils 100 Männern und Frauen zwischen 46 und 74 Jahren mit Adrenopause, um die individuelle DHEA-Dosis zu ermitteln, welche Tageshöchstwerte von DS, gemessen 3–5 h nach morgendlicher DHEA-Gabe, zwischen 2,0 und 2,8 µg/ml bei Frauen und 4 und 5 µg/ml bei Männern erreichen lässt. Dies entspricht den Blutspiegeln gesunder Erwachsener im dritten Lebensdezennium. Ergebnisse: Für diese Vorgaben waren 5, 10, 15, 25 oder 50 mg DHEA bei jeweils 18, 26, 34, 19 und 3% der Frauen sowie 15, 25, 50, 75 oder 100 mg DHEA bei 5, 13, 51, 17 und 14% der Männer erforderlich. Hierdurch veränderten sich die Blutspiegel (Mittelwert ± SD) signifikant (p < 0,01): a) bei den Frauen bei DS von 0,7 ± 0,4 auf 2,4 ± 0,5 µg/ml, bei Testosteron von 0,4 ± 0,4 auf 0,9 ± 0,5 pg/ml und bei Androstendion von 0,8 ± 0,4 auf 1,4 ± 0,4 ng/ml sowie b) bei den Männern bei DS von 1,4 ± 0,5 auf 4,1 ± 0,7 µg/ml, bei freiem Testosteron von 10,9 ± 4,1 auf 14,7 ± 4,5 pg/ml, bei Androstendion von 1,2 ± 0,5 auf 2,0 ± 0,6 ng/ml, bei Östron von 28 ± 14 auf 41 ± 19 pg/ml und bei Östradiol von 16 ± 8 auf 31 ± 15 pg/ml. Bei inadäquater Dosis wurden Nebenwirkungen wie Müdigkeit, Ruhelosigkeit, Migräne, Akne/Hirsutismus, Effluvium und Odor bei jeweils 34, 17, 9, 31, 21 und 11% der Frauen festgestellt, die sich nach Dosisadjustierung auf 8, 2, 4, 6, 7 und 0% der Frauen signifikant reduzierten (p < 0,05; p < 0,2 bei Migräne). Schlussfolgerung: Wir empfehlen, eine DHEA-Substitution der Adrenopause mit einer individuell adjustierten niedrigen Dosis von 5–50 mg bei Frauen und 15–100 mg bei Männern in den physiologischen Bereich junger Erwachsener hinein durchzuführen. Dies hat sich nach unseren vorläufigen Daten aus den letzten 5 Jahren sowohl klinisch als auch bezüglich der Patienten-Compliance gut bewährt. Eine überphysiologische Pharmakotherapie mit DHEA erscheint dagegen bei speziellen Erkrankungen wie Kollagenosen indiziert.
Mental Rotation of Perspective Stimuli in a California Sea Lion (Zalophus californianus)
Authors: Stich Kai Petra , Dehnhardt Guido , Mauck Björn
Published: April 2003

The time it takes humans to discriminate rotated objects from their mirror images increases linearly with the rotation angle. This phenomenon is probably due to an analogue mode of visual information processing during which an object’s mental representation is rotated in a time-consuming process called mental rotation. As the speed of mental rotation in humans depends on rotation axis, we tested the ability of a California sea lion to mentally rotate perspective line drawings of three-dimensional objects about four axes. In a matching-to-sample experiment the animal was presented with the image and a mirror image of a block sample that had previously been shown upright. Both image and mirror image were rotated by a multiple of 60° about the object’s x-, y-, z-axis, or a skew axis (an axis oblique to these standard orthogonal axes). The animal’s choice and reaction times were recorded using a computer-controlled touch-screen device. Mean reaction times and errors generally increased with angular disparity supporting the model of mental rotation for three-dimensional objects. Linear regression analysis of mean reaction times yielded high correlation coefficients only for three axes. The slope of reaction time functions indicated the highest mental rotation speed for the skew axis. This contrasts with the priority of mental rotation axes in humans suggesting that due to special ecological demands a different mode of orientation invariance evolved in marine mammals.
Neonatal 6-Hydroxydopamine Administration to Mice Is Fatal
Authors: Brot Michelle D. , Szczypka Mark S. , Reavell Randy , Marck Brett T. , Matsumoto Alvin M. , Palmiter Richard D.
Published: April 2003

Depletion of dopamine in adult rats by treatment with the neurotoxin 6-hydroxydopamine (6-OHDA) causes severe deficits in feeding, drinking, and movement that often lead to death. However, when neonatal rats are treated similarly, they survive normally, suggesting that compensatory adaptation to dopamine depletion occurs. In contrast, dopamine-deficient mice that have a selective genetic deficiency in dopamine production die 2–4 weeks after birth. Thus, we tested the hypothesis that killing dopaminergic neurons with 6-OHDA might promote survival of dopamine-deficient mice. Body weights, motor coordination, catecholamine levels, and survival were monitored for several weeks after bilateral administrations of 6-OHDA to 3-day-old mice. Some treated mice were raised in a heated chamber to help them conserve energy. The results demonstrate that regardless of genotype or environmental temperature, bilateral neonatal 6-OHDA lesions are lethal to mice.
Effect of Isosorbide Dinitrate Ointment on Anal Fissure
Authors: Songun I. , Boutkan H. , Delemarre J.B.V.M. , Breslau P.J.
Published: April 2003

Background/Aims: Until recently, the treatment of choice for anal fissure was surgery, consisting of a partial lateral internal sphincterotomy. This treatment has a high complication rate: impaired continence is reported in 8–30% of the patients in the literature. Therefore, recently nonsurgical treatment modalities have been developed, such as local application of isosorbide dinitrate (ISDN) ointment. This treatment has comparable effectiveness with lower complication rates. To study the effect of ISDN on the healing of anal fissures in a general surgical practice, a prospective study was performed in our hospital. Methods: In the period between June 1997 and January 2000, 100 consecutive patients with anal fissure were treated with ISDN. Results: Of these 100 patients, 93 were healed within 8 weeks and 7 patients had no response and were operated. Of the 93 patients with primary healing fissures, 13 patients had recurrence during the 1-year follow-up. Seven of them were cured with ISDN, and the remaining 6 patients needed surgery. The only complication observed in this study was temporary headache which was observed in 7 patients. Conclusions: The primary healing rate of anal fissures was 93% with ISDN. In case of recurrence, 54% (7/13) could again be treated successfully with ISDN. Therefore, we recommend ISDN as first choice treatment for primary and recurrent anal fissures.
Long-Term Outcomes of Intragastric Endoscopic Mucosal Resection Using a Modified Buess Technique for Early Gastric Cancer
Authors: Nakagoe Tohru , Tanaka Kenji , Yasutake Toru , Sawai Terumitsu , Tsuji Takashi , Nanashima Atsushi , Shibasaki Shin-ichi , Yamaguchi Hiroyuki , Ayabe Hiroyoshi
Published: April 2003

Background/Aims: The aim of this study was to clarify long-term outcomes of endoscopic mucosal resection (EMR) using a modified Buess technique for mucosal gastric cancer. Methods: The procedure included en bloc mucosal resection using a Buess-type rectoscope into the gastric lumen via a temporary gastrostomy under video camera guidance. We reviewed 5 patients who underwent this procedure between 1995 and 1997 with a single mucosal cancer of the stomach that was unsuitable for en bloc excision by endoscopic snare diathermy. Results: All tumors were superficial elevated types (type 0–IIa) located in the middle third and posterior wall of the stomach. Median maximum tumor diameter was 2.2 (range 1.1–3.5) cm. There was no operative mortality. One patient developed a hemorrhagic gastric ulcer postoperatively. All tumors histologically showed curative potential of the mucosal resection without margin involvement. During a median follow-up period of 64 (50–77) months, none of the patients developed local recurrence. One patient had an early gastric cancer that metachronously developed at another stomach site. Conclusion: Intragastric EMR using a modified Buess technique appears to be a useful treatment for cure of mucosal gastric cancer for a limited group of patients unsuitable for complete en bloc excision by endoscopic snare diathermy.
Intravenously Administered Human Epidermal Growth Factor in the Rat
Authors: Jansen C. , Nexø Ebba , Ihse I. , Axelson J.
Published: April 2003

Background/Aim: Epidermal growth factor (EGF) is known to exert mitogenic effects in different tissues, including the digestive tract and pancreas. EGF is also found in high concentrations in pancreas. Infusion of human EGF has been shown to induce proliferation of cells in exocrine pancreas, and to increase the thickness of the small intestine. The aim of this study was to investigate the influence of intravenously administered human EGF on pancreatic and biliary secretions in the rat. Materials and Methods: Rats were fasted overnight and were given human EGF intravenously, either as a bolus dose of 5 µg or as a continuous infusion in increasing doses from 0.5 to 10 µg/h. Bile and pancreatic juice were either collected together or separately. The concentration of human EGF in bile and pancreatic juice was measured. Results: After a bolus dose of EGF increased bile/pancreatic secretion was seen after 60 and 90 min when the bile and pancreatic secretions were not separated. Continuous infusion of EGF increased the joint secretion rate of bile and pancreatic juice in a dose-dependent manner. No effect on secretion rate was seen when bile and pancreatic juice were collected separately. After intravenous infusion of human EGF a 1,000-fold increase of human EGF excretion was found in bile but not in pancreatic juice. Conclusion: Intravenously administered human EGF was excreted in high concentrations in bile and increased the secretion rate of pancreatic juice when collected together with bile. The results suggest that EGF, at least partly, exerts its effect on the pancreas and the proximal gastrointestinal tract after excretion with bile and stimulates pancreatic secretion via this route.
Involvement of IL-18 and Soluble Fas in Patients with Postoperative Hepatic Failure
Authors: Nakae H. , Zheng Y.-J. , Wada H. , Tajimi K. , Endo S.
Published: April 2003

We measured the levels of tumor necrosis factor alpha (TNF-α), interleukins (IL)-6 and -18, and soluble Fas (sFas) in 11 patients with postoperative hepatic failure and assessed whether IL-18-mediated apoptosis is involved in the onset of liver dysfunction. The serum TNF-α, IL-18, and sFas levels were significantly higher in patients with sepsis as a complication than in those without sepsis. The TNF-α and IL-18 levels were significantly higher in nonsurvivors than in survivors. Significant correlations were observed between TNF-α and IL-6, between TNF-α and IL-18, and between TNF-α and sFas levels. These results showed that Fas-mediated hepatocyte apoptosis functions as an important mechanism responsible for the onset of postoperative hepatic failure in humans. They especially suggested that IL-18 and TNF-α function both as apoptosis-promoting factors and as apoptosis-inhibiting factors, depending on the conditions to which hepatocytes are subjected.
Causal Interactions, Fuzzy Sets and Cerebrovascular ‘Accident’: The Limits of Evidence-Based Medicine and the Advent of Complexity-Based Medicine
Authors: Helgason Cathy M. , Jobe Thomas H.
Published: April 2003

In evidence-based medicine, stroke subtype is diagnosed after a sequential search for etiology; the first positive test result of significant severity rounds off to one overwhelming cause. Degree of severity, interaction among variables, and concomitant variable conditions are not considered in defining the cause of stroke. Yet, thrombus formation, and possibly vascular rupture, is an interactive process involving the vascular wall, flow properties of the blood and blood constituents; this process occurs in homeostasis and pathology. Evidence-based medicine ignores this process and instead studies stroke using crisp ‘all or none’ classification where subtypes are distinct and interactively relate only to outcome. As a result, scientific inquiry is focused on prediction for the collective of patients. The statistical approach of evidence-based medicine is founded on probability theory, itself rooted in classical set theory where elementhood is all (1) or none (0), and opposites interact only to form the null set. Fuzzy set theory, where set membership is to degree [0, 1], encompasses classical set theory, allows for an interactive process between variables, and therefore becomes the measure of complexity. Fuzzy set theory can change the scientific method of evidence-based medicine.
Creutzfeldt-Jakob Disease Mortality in Italy, 1982–1996
Authors: Arpino Carla , Conti Susanna , Masocco Maria , Toccaceli Virgilia , Ladogana Anna , D’Alessandro Marco , Pocchiari Maurizio
Published: April 2003

We report an estimate of Creutzfeldt-Jakob disease (CJD) deaths in Italy from 1982 to 1996 by using mortality data based on a retrospective review of deaths taken from the mortality data base of the Italian Census Bureau (ISTAT, years 1982–1993), and on the prospective surveillance performed by the Italian National Register of CJD (years 1993–1996). One hundred and ninety-five and 154 deaths attributed to CJD were recorded by ISTAT and the CJD register, respectively. The average annual age-adjusted mortality rate was 0.45 and 0.84 deaths per million for the period 1982–1993 and 1993–1996, respectively. The yearly increase in the number of CJD deaths was mostly due to a rise in the reported deaths among people older than 60 years. The result of the linkage between ISTAT and the CJD register shows that the integrated age-adjusted mortality rate for 1993 was about 1 case per million, similar to the rates observed in other studies and obtained by the CJD register alone in 1996. This study indicates that the data of the CJD register is accurate and therefore important for assessing eventual changes in the characteristics of the disease resulting from bovine spongiform encephalopathy or other new risk factors.
The Concept of an Immune Mechanism of Chemical Homeostasis and Its Importance in Biology and Medicine
Authors: Bykova A. , Baker E.
Published: April 2003

This paper outlines research that has led to the concept of the inevitable participation of the immune system in an organism’s chemical homeostasis. This function of the immune system is tentatively named the ‘immune mechanism of the chemical homeostasis’ (IMCH). It is based on the theory of a permanent physiological synthesis of antibodies to endogenous biologically active substances. Minimal accumulation of biologically active substances as a result of the influence of different factors specifically activates the immune system in order to maintain its chemical homeostasis. The concept suggests the necessity of widening the notion of the range of the immune system’s censorial functions. The concept explains the preexistence of immunocompetent cells preadapted to biologically active substances and autoantibodies specific to them; the natural clonality of the B lymphocyte pool; the polyclonal lymphocyte activation triggered by mitogens, foreign proteins, erythrocytes, and microbes, and tolerance to drugs.
Apoptosis Induced in T Cells by Human Neuroblastoma Cells: Role of Fas Ligand
Authors: Shurin Galina V. , Gerein Valentin , Lotze Michael T. , Barksdale Jr. Edward M.
Published: April 2003

The CD95/CD95L (Fas/Fas ligand) receptor/ligand system plays an important role in regulation of cell survival and induction of a programmed cell death. It is also involved in regulation of effector phase of T and NK cell cytotoxicity, establishment of immune privilege sites, and tumor escape from immune recognition. In this study, we assessed expression of CD95L in tumors obtained from patients with neuroblastoma (NB) and in established NB cell lines. We measured the presence of intratumoral T cell infiltrates and T cell survival in tumor tissue samples. High levels of apoptosis were observed in tumor-associated lymphocytes as well as in Jurkat T cells cocultured with NB cells in vitro. T cell death was reduced after treatment of NB cells (in vitro) with antibody to FAS ligand (FasL). Overall, our data suggest that NB-induced apoptosis of Fas-sensitive Jurkat T cells is mediated by functional FasL expressed on NB and Fas/FasL interaction may be responsible for the elimination of T cells in the NB microenvironment.
Allosteric Modulation of Native Cochlear P2X Receptors: Insights from Comparison with Recombinant P2X2 Receptors
Authors: Kanjhan Refik , Raybould Nicholas P. , Jagger Daniel J. , Greenwood Denise , Housley Gary D.
Published: April 2003

Extracellular adenosine 5′-triphosphate (ATP)-gated ion channels assembled from P2X receptor subunits exhibit subunit-selective allosteric modulation by protons and divalent cations. In voltage-clamped guinea-pig cochlear outer hair cells (OHC) and Deiters’ cells (DC), H+ and Cu2+, but not Zn2+, enhanced the P2X receptor-mediated inward currents. Acid pH (6.5) potentiated OHC ATP-gated currents by 45%. Co-application of Cu2+ (1–40 µM) with ATP increased the response by 20%. In DCs, ATP-gated currents were potentiated 85% by acid pH, and 70% by Cu2+. Alkaline pH inhibited ATP-gated inward currents by 73% in OHCs and 85% in DCs. Zn2+ was either ineffective (1–10 µM) or inhibitory (40–400 µM). Recombinant rat P2X2 receptor-mediated inward currents in Xenopus oocytes displayed allosteric modulation that was different from the native guinea-pig cochlear P2X receptors. The oocyte ATP-gated inward current was potentiated 450% by shifting from pH 7.5 to pH 6.5, and 130% with 40 µM Cu2+. The enhanced response to ATP with acid pH and Cu2+ is a signature of the P2X2 subunit. In contrast to native guinea-pig cochlear cells, extracellular Zn2+ (40 µM) increased the recombinant ATP-gated inward current by 200% in oocytes. These results suggest that the positive allosteric modulation of cochlear OHC and DC ATP-gated ion channels by protons and Cu2+ arises in part from the P2X2 receptor subunit, with additional regulatory elements.
Modeling Relationships between Various Domains of Hearing Aid Provision
Authors: Meister Hartmut , Lausberg Isabel , Kiessling Jürgen , von Wedel Hasso , Walger Martin
Published: April 2003

Various inventories have been developed to quantify the success of hearing aid provision. Though numerous parameters including initial measures (hearing disability, handicap) or ‘outcome measures’ (e.g. benefit, satisfaction and usage) are recorded, relationships and interactions among them are still unclear. A study applying a questionnaire addressing 11 domains relevant to amplification was conducted in order to generate different psychometric models with the AMOS© software package for structural equation modeling. The models expose easily interpretable interactions and are helpful in understanding effects occurring with commonly used outcome measures: benefit reflects the difference between the aided and unaided condition but additionally comprises the importance of the hearing aid within a specific situation. Satisfaction is highly reliant on benefit. Usage is strongly dependent on the severity of hearing problems and therefore not appropriate in assessing the success of amplification. Moreover, the models help to predict the outcome of clinically used inventories (i.e. the Glasgow Hearing Aid Benefit Profile).
The Middle Cerebral Artery Flow Velocities during Head-Up Tilt Testing in Diabetic Patients with Autonomic Nervous System Dysfunction
Authors: Žvan Bojana , Zaletel Marjan , Pretnar Oblak Janja , Pogačnik Tomaž , Kiauta Tomaž
Published: April 2003

Background: The goal of this study was to examine the effects of diabetes mellitus on the trend of mean arterial velocity (vm) in both middle cerebral arteries during head-up tilt (HUT). Methods: The study was performed in 20 patients, 9 females and 11 males (mean age 51 ± 12 years) with an average 17-year history of insulin-dependent diabetes mellitus type I or II and a dysfunction of the autonomic nervous system confirmed by cardiocirculatory tests [Valsalva maneuver, deep breathing test, handgrip test, orthostatic test and spectral analysis of heart rate (HR) variability], and 19 age-matched healthy volunteers, 9 females and 10 males (mean age 48 ± 6.8 years). vm was measured by a transcranial Doppler monitoring system during a 5-min baseline period, followed by a 5-min HUT in the upright position (90°). Mean arterial blood pressure (MAP), HR and end-tidal CO2 (Et-CO2) were monitored concomitantly. Results: In healthy volunteers, vm decreased stepwise during the first minute of HUT, reaching a minimum during the last 2 min of the test (vm: basal 63.0 ± 11.7 cm/s, 1st min 57.6 ± 12.2 cm/s, 2nd min 55.9 ± 12.6 cm/s, 3rd min 53.4 ± 12.6 cm/s, 4th min 52.1 ± 12.7 cm/s, 5th min 51.3 ± 13.5 cm/s). In the supine position, vm recovered and reached the resting vm values. It declined gradually during HUT and less steeply in diabetic (vm: basal 54.4 ± 10.1 cm/s, 1st min 51.96 ± 9.3 cm/s, 2nd min 50.7 ± 11.6 cm/s, 3rd min 50.5 ± 11.4 cm/s, 4th min 49.5 ± 10.7 cm/s, 5th min 48.8 ± 11.5 cm/s) than in healthy subjects. vm differed significantly (p = 0.00) between rest and HUT in both groups. The differences in MAP, HR and Et-CO2 during rest and HUT between the groups were not statistically significant (p ΔMAP = 0.36, p ΔHR = 0.86, p ΔEt-CO2 = 0.97). The results of the analysis of variance of vm for repeated measurements between the two groups of subjects were highly significant (p = 0.00). The model of linear regression analysis was significant (p = 0.007). Diabetes was significant in the model (p = 0.00), while ΔMAP, ΔHR and ΔEt-CO2 were not. Conclusions: These findings may indicate that vasomotor responses during HUT testing are decreased in diabetic patients.
Gamma Knife Radiosurgery for Treatment of Trigeminal Neuralgia in Multiple Sclerosis Patients
Authors: Huang Eugene , Teh Bin S. , Zeck Otto , Woo Shiao Y. , Lu Hsin H. , Chiu J. Kam , Butler E. Brian , Gormley William B. , Carpenter L. Steven
Published: April 2003

Background: Trigeminal neuralgia is a paroxysmal pain syndrome commonly associated with multiple sclerosis. While gamma knife radiosurgery has been shown to be an effective treatment for most cases of trigeminal neuralgia, it is considered to be less efficacious in patients with multiple sclerosis and less viable as a treatment option. Methods: Seven patients with multiple-sclerosis-associated trigeminal neuralgia were identified from 50 consecutive patients treated for trigeminal neuralgia at the Memorial-Hermann Gamma Knife Radiosurgery Center. A Leksell gamma knife was used to deliver 80 or 90 Gy to a single 4-mm isocenter targeting the fifth nerve root entry zone into the pons. The patients were followed for a median period of 28 months and graded on a scale of 1 to 5, adopted from the Barrow Neurological Institute. Results: All 7 patients showed excellent responses to radiosurgery with complete resolution of their pain and cessation of pain medications. The time to maximal response varied from 1 day to 8 months after treatment. The only complication was persistent facial numbness over the distribution of V2 and V3 which occurred in 4 patients. One patient experienced a recurrence of pain (grade 3) 24 months after radiation treatment, and she is currently being treated with carbamazepine. Conclusions: Gamma knife radiosurgery is an effective treatment option for trigeminal neuralgia patients with multiple sclerosis. These patients should be informed that there appears to be a higher incidence of facial numbness and that a longer period of several months should be allowed before the full effects of treatment may be observed as compared to the general population.
Where There’s a Web, There’s a Way: Commercial Genetic Testing and the Internet
Authors: Williams-Jones Bryn
Published: April 2003

The Internet has become a ‘global marketplace’, enabling consumers to purchase health care products and services, including genetic testing, through a variety of national and international sources. A web search for commercial (for-profit) genetic testing companies found 12 with a web presence that were offering adult genetic susceptibility testing, of which 3 offered direct-to-consumer access. In this paper, Canada – with its educated population and universal health care system – will serve as a case study for illustrating the social, ethical and policy issues (e.g., information privacy, just access to health care, product safety, and access to unbiased health information) arising with Internet-based access to commercial genetic testing. Health professionals, policy makers and consumers in all developed nations will be faced with complex technical, social and ethical issues, but without further discussion it will not be possible to determine how best to manage and maximise the benefits of this increased accessibility and choice, while minimising the associated personal and social costs.
Anti-Mouse Mesangial Cell Serum Induces Acute Glomerulonephropathy in Mice
Authors: Yo Yoshikage , Braun Michael C. , Barisoni Laura , Mobaraki Hideko , Lu Huiyan , Shrivastav Shashi , Owens Jennie , Kopp Jeffrey B.
Published: April 2003

In order to develop a model in mouse similar to anti- Thy-1 nephritis in the rat, we prepared sheep antiserum against SV40-transformed mouse mesangial (MES 13) cells. In vivo, the anti-mouse mesangial cell serum-treated mice showed severe azotemia that peaked at day 6 and proteinuria that peaked at day 8, in a dose-dependent fashion. Light microscopy and electron microscopy showed duplication of glomerular basement membranes, mesangiolysis, subendothelial and mesangial electron-dense deposits, and foot process effacement. Intraglomerular tuft cell number was significantly reduced at day 4 and there were increased numbers of apoptotic cells at days 2 and 4. SCID mice and mice lacking C3 manifested similar responses to anti-mouse mesangial cell serum, suggesting that T cells, B cells and complement are not required for glomerular injury in this model. In vitro, anti-mouse mesangial cell serum treated mesangial cells showed greater release of lactate dehydrogenase, decreased cell survival, and increased apoptotic cell death. Anti-mouse mesangial cell serum induces glomerulopathy characterized by mesangiolysis and mesangial cell apoptosis, and followed by cellular proliferation.
Caspase-9 Takes Part in Programmed Cell Death in Developing Mouse Kidney
Authors: Araki Takashi , Hayashi Matsuhiko , Nakanishi Keiko , Morishima Nobuhiro , Saruta Takao
Published: April 2003

Programmed cell death is a mechanism by which organisms dispose of unwanted cells, and it is thought to be an important process in organogenesis. We have already reported the role of caspase-3 in the developing metanephros. While caspase-3 is thought to be positioned downstream of the caspase-activating cascade, the upstream caspase for programmed cell death in the developing kidney is still unknown. In an attempt to identify it, we blocked caspase activity in metanephric explants with caspase inhibitors. Administration of a caspase-9 inhibitor (Ac-IETD-CHO) effectively prevented both ureteric bud branching and nephrogenesis, the same as a caspase-3 inhibitor (Ac-DEVD-CHO). On the other hand, administration of a caspase-8 inhibitor (Ac-LETD-CHO) did not inhibit ureteric bud branching or nephrogenesis. Apaf-1, which executes programmed cell death in the caspase-9-related pathway, was detected in the cells exhibiting caspase-9 activity, and our results suggest that Apaaf-1/caspase-9 activates caspase-3 in kidney organogenesis.
Ischemic Preconditioning of Renal Tissue: Identification of Early Up-Regulated Genes
Authors: Damario Gomes Marcelo , Vasconcelos Cancherini Douglas , Amaral Rebouças Moreira Marise , Amaral Rebouças Nancy
Published: April 2003

Given the important effects of ischemic preconditioning (IPC) in minimizing tissue damage induced by sustained ischemia in several tissues, this study evaluated the effect of IPC in preserving renal function and identified up-regulated genes after 30 min of preconditioning. IPC induced by 2, 3 and 4 min of ischemia, intercalated by 5 min of reperfusion, induced a measurable protection of renal function and morphology. The improved functional and histological parameters occurred in parallel with up-regulation of 39 genes, as evaluated by subtractive hybridization; for 13 of them we could show, by RNAse protection assay, a significant increase in mRNA levels. These genes code for chaperones/chaperonins and cytoskeleton proteins that could be involved in preservation of protein folding and cellular structures after sustained ischemia; proteins related to oxidative metabolism that might be relevant for cellular use of alternate sources of energy or for faster recovery of ATP levels in this condition, and proteins that are putative scavengers of oxidant products. Summarizing, ischemic preconditioning induced up-regulation of genes that code proteins whose functional roles suggest their involvement in the tolerance of the preconditioned tissue to sustained ischemia.