bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Effects of Childhood Obesity on Morbidity and Mortality
Authors: Maffeis Claudio , Tatò Luciano
Published: April 2003

Obesity tracks from childhood into adulthood, and the persistence of obesity rises with age among obese children. Early onset obesity was suggested as a risk factor for morbidity and mortality later in life. In both sexes, rates of diabetes, coronary heart disease, atherosclerosis, hip fracture and gout were increased in those who were overweight as adolescents. Especially in females, obesity at late adolescence was associated with several and relevant psychosocial consequences in adulthood. Finally, a higher mortality risk for all causes of death, especially atherosclerotic cerebrovascular disease and colorectal cancer, was demonstrated in males but not in females who were overweight during high school years. Although the persistence of excess adiposity from childhood to adulthood is a morbidity risk factor, it is not known if total body fat or body fat distribution is the main factor responsible. In particular, a specific role for the intra-abdominal adipose tissue (IAAT) in childhood, independently from that of total body fat, on morbidity risk in adulthood was not demonstrated yet. The association between childhood obesity and adult morbidity and mortality strongly suggests that a more effective prevention and treatment of childhood obesity should be pursued.
Insulin and Insulin-Like Growth Factor I Receptors: Similarities and Differences in Signal Transduction
Authors: Dupont Joelle , LeRoith Derek
Published: April 2003

The insulin receptor (IR) and the insulin-like growth factor I receptor (IGF-IR) belong to the same subfamily of receptor tyrosine kinases with two extracellular α-subunits and two transmembrane β-subunits. They share a high similarity of structure and intracellular signalling events. However, the IR and the IGF-IR mediate different effects on metabolism, cell proliferation, apoptosis and differentiation. Although some of the variation can be attributed to a different tissue distribution or subcellular localization, it can also be explained by structural differences in the β-subunit, which may result in activation of specific substrates and signal pathways.
Short-Term Tools to Measure Responsiveness to Growth Hormone Replacement
Authors: Jørgensen Jens O.L. , Hansen Troels K. , Conceição Flávia Lucia , Christensen Jens J. , Vahl Nina , Christiansen Jens Sandahl
Published: April 2003

Growth hormone (GH) replacement is a prolonged and expensive treatment modality which involves daily subcutaneous injections in children and adults. Efforts have been made, therefore, to develop short-term tests to predict long-term clinical response. The so-called insulin-like growth factor I (IGF-I) generation test was originally introduced in order to select responders to GH among short children without classical GH deficiency. A positive correlation between short-term increase in serum IGF-I and linear growth has, however, only been reported in a minority of studies. There is no single outcome measure available in GH-deficient adults, and no evidence of a correlation between IGF-I and the effects of GH replacement on factors such as body composition or physical fitness. In conclusion, no reliable short-term test to predict long-term response to GH replacement is available in either children or adults. For safety reasons, however, measurement of serum IGF-I concentrations in GH-deficient patients remains an important means of monitoring during GH replacement.
Body Composition and Quality of Life as Markers of the Efficacy of Growth Hormone Replacement Therapy in Adults
Authors: Svensson Johan , Johannsson Gudmundur , Bengtsson Bengt-Åke N.-Å.
Published: April 2003

Growth hormone (GH) replacement therapy in GH-deficient adults should be initiated with a low dose, independent of body weight or body surface area. Measurements of serum insulin-like growth factor I (IGF-I) concentrations, as well as clinical examinations aimed at detecting signs of fluid excess, are important as safety markers to avoid overtreatment with GH. At present, there is no optimal marker for the long-term efficacy of GH replacement therapy. The long-term maintenance dose of GH should, therefore, be titrated in each individual based on the clinical response, with the aim of normalizing body hydration, other measurements of body composition, quality of life and well-being, and biochemical indices such as serum IGF-I concentration.
Normal Values of Insulin-Like Growth Factor I and Their Clinical Utility in Adults
Authors: Strasburger Christian J. , Bidlingmaier Martin , Wu Zida , Morrison Katherine M.
Published: April 2003

The concentration of circulating insulin-like growth factor I (IGF-I) is a potential marker for growth hormone (GH) deficiency in adults. Indeed, researchers have shown that IGF-I levels are of greater diagnostic value than other possible markers, such as IGF-binding protein 3 (IGFBP-3) and the acid-labile subunit (ALS). Accurate age-matched normative data are essential to give patient data diagnostic meaning. Such data are assay specific and must exclude those individuals with certain confounding medical conditions. Post-diagnosis, monitoring of IGF-I and IGFBP-3 levels can be used to assess the efficacy and safety of GH replacement therapy. Furthermore, IGF-I levels, and possibly ALS levels, can be used to aid the diagnosis and monitoring of acromegaly. For example, acromegaly can be excluded in patients with normal IGF-I levels if liver failure and malnutrition/malabsorption are ruled out.
Comparison of Dialysis and Clinical Characteristics of Patients with Frequent and Occasional Hemodialysis-Associated Hypotension
Authors: Tislér András , Akócsi Katalin , Hárshegyi Ibolya , Varga Gábor , Ferenczi Sándor , Grosz Mária , Kulcsár Imre , Löcsey Lajos , Sámik József , Solt István , Szegedi János , Tóth Eszter , Wágner Gyula , Kiss István
Published: April 2003

Background: Symptomatic dialysis hypotension (DH) continues to be a common problem. By comparing patients prone and resistant to DH, several dialysis session and patient related characteristics have been identified that confer susceptibility to DH. Less is known, however, about the comparison of patients with frequent and only occasional DH. The aim of the study was to compare clinical and dialysis-session- (complicated by hypotension) related data between those with frequent (fDH) and those with occasional dialysis hypotension (oDH). Methods: Nine hundred and fifty-eight patients at 11 dialysis units were followed for 10 months and characteristics of patients with fDH (≧10 hypotensive events necessitating medical intervention) (n = 96) were compared to that of patients with oDH (1 or 2 events/10 months) (n = 130). Significant and independent predictors of fDH were obtained by multivariate logistic regression. Results: Significant differences between fDH vs. oDH patients were older age (64.4 vs. 56.9 years, p < 0.001), more females (66 vs. 46%, p < 0.005) in fDH. More fDH patients had diabetes (27 vs. 15%, p < 0.05) and less had glomerulonephritis (15 vs. 35%, p < 0.001) as the cause for ESRD. Coronary artery disease (68 vs. 50%, p < 0.01) and long-acting nitrate treatment (51 vs. 30%, p < 0.001) was more frequent while treatment with ACEI (33 vs. 48%, p < 0.05) or Ca-channel blockers (40 vs. 53%, p < 0.05) were less frequent in patients with fDH. Patients with fDH had higher serum phosphorus levels (1.99 vs. 1.79 mmol, p < 0.005). Dialysis session related data were similar but the hypotensive episode occurred earlier during dialysis in fDH (136 vs. 156 min, p < 0.01). In multivariate analysis, significant independent predictors of fDH were older age (OR = 1.04 [1.02–1.07]), lack of glomerulonephritis as renal diagnosis (2.63 [1.18–5.87]), high phosphorus levels (5.0 [2.45–10.0]), lack of use of Ca-channel blockers (2.09 [1.12–3.91]), and the use of nitrates (2.38 [1.24–4.55]). Conclusion: Features of the dialysis sessions complicated by DH seem to be similar between patients with fDH and oDH, while patient characteristics such as older age, renal diagnosis other than glomerulonephritis, higher serum phosphorus levels, use of nitrates, and lack of use of calcium channel blockers are significantly and independently associated with fDH.
Treatment of Cutaneous T Cell Lymphoma
Authors: Stadler R.
Published: April 2003

Primary cutaneous T cell lymphomas encompass a wide variety of lymphomas that are characterized by a distinct clinical presentation. Advanced biological techniques have allowed a more precise classification in recent years. Stage-adapted therapy is at present the best approach to treat cutaneous T cell lymphoma.
Dermal Toxicity due to Industrial Chemicals
Authors: Mathur A.K. , Khanna S.K.
Published: April 2003

The dermal toxicity due to industrial chemicals is well recognised. They may be the cause of skin irritation and skin sensitization. Some of the chemicals may result in dermal reactions such as changes in skinfold thickness, cellular degeneration and necrosis. The absorption through the skin may also cause penetration of chemicals into the organism causing systemic effects.
Urea and Sodium Chloride in Moisturisers for Skin of the Elderly – A Comparative, Double-Blind, Randomised Study
Authors: Kuzmina Natalia , Hagströmer Lena , Emtestam Lennart
Published: April 2003

Urea has long been used to treat dry skin. In the present report, we compared two identical creams, with the exception that one contained both urea and sodium chloride and the other urea alone, in 23 healthy elderly subjects. Following a 2-week wash-out, their clinically non-eczematous, rough- or normal-appearing skin on the anterior proximal part of the lower legs was treated twice daily in a double-blind and randomised manner. We examined the treated areas by measuring transepidermal water loss, capacitance and electrical impedance. Our findings suggest that both moisturisers seem equally effective, at least concerning the ability to reverse impedance indices towards normal, an effect ascribed to changes in hydration of the stratum corneum. However, the relevance of the impedance parameters to the clinical picture is disputable and further studies of moisturisers in elderly subjects are needed.
Percutaneous Absorption Studies of Octamethylcyclotetrasiloxane Using the Human Skin/Nude Mouse Model
Authors: Zareba Grazyna , Gelein Robert , Morrow Paul E. , Utell Mark J.
Published: April 2003

Octamethylcyclotetrasiloxane (D4) has been used for more than 40 years in industrial applications and consumer products, including the personal care industry. D4 possesses many properties suitable for personal care products, such as low surface tension, water repellency, and thermal and chemical stability. The skin is a major route of exposure to D4 for humans. The main objective of this study was to evaluate the percutaneous absorption of neat D4 in human skin using the human skin/nude mouse model. This information is needed to aid in assessing potential risks associated with the intended use of D4. To determine whether D4 accumulates in adipose tissue of the skin, the distribution of D4 in human skin layers following application of neat D4 was also evaluated. In this study, a mean of 1.09 ± 0.46% of the applied dose was absorbed by the animal under semioccluded conditions. Only about 0.02% of the applied dose remained in the skin after 24 h of exposure (or 72 h after application). The majority (94.59 ± 12.28%) of the dose evaporated from the site. Excretion in the volatile trap (or expired volatiles) accounted for 42% of the radioactivity that was absorbed, while 49% were excreted in the urine and feces. Despite the lipophilic properties of D4, a significant accumulation of D4 in adipose tissue of the skin was not observed 24 h following application to the surface of the skin. The small amount of D4 detected in the skin was distributed mainly in the epidermis (61%), with lower amounts in the dermis (29%) and subcutaneous adipose tissue (10%). Dermal absorption studies using human skin transplanted onto nude mice showed that this model could be successfully applied for in vivo percutaneous absorption studies of D4, and presumably of other cyclic siloxanes. The fraction of the percutaneous dose of D4 absorbed in this model was found to be consistent with results reported by others using different experimental approaches.
Effects of Oral Acitretin on Contrast Sensitivity and Tear Film Function: A Prospective Study
Authors: Gartaganis S.P. , Mela E.K. , Georgakopoulos C.D. , Georgiou S. , Monastirli A. , Merk H.F. , Tsambaos D.
Published: April 2003

The purpose of this prospective study was to investigate the ocular side effects of short-term therapy with oral acitretin (1 mg/kg/day) in 24 patients with severe and recalcitrant dermatoses. Apart from the routine ophthalmological examination, the following tests were performed: break-up time of tear film for the determination of its stability, Schirmer test for the assessment of lacrimal gland function, rose bengal staining for the detection of possible ocular surface damage and contrast sensitivity test for the evaluation of visual function. No statistically significant differences could be found between the pretreatment values of the assessed parameters and those obtained after 1 and 2 months of therapy. It seems reasonable, therefore, to suggest that ocular surface integrity and tear film and visual function are not affected by short-term oral acitretin administration.
Evolutionary Convergence in Nervous Systems: Insights from Comparative Phylogenetic Studies
Authors: Nishikawa Kiisa C.
Published: April 2003

Over the past 20 years, cladistic analyses have revolutionized our understanding of brain evolution by demonstrating that many structures, some of which had previously been assumed to be homologous, have evolved many times independently. These and other studies demonstrate that evolutionary convergence in brain anatomy and function is widespread. Although there are relatively few neuroethological studies in which brain and behavior have be studied within an evolutionary framework, three relatively well studied cases are reviewed here: electric communication among gymnotiform and mormyriform fishes, prey capture among frogs, and sound localization among owls. These three examples reveal similar patterns of brain evolution. First, it is clear that novel abilities have evolved many times independently in taxa whose common ancestors lack these abilities. Second, it is apparent that small changes in neural pathways can lead to dramatic changes in an organism’s abilities. Brain evolution at this small scale is quite common. The behavioral importance of small scale changes on one hand, and the pervasiveness of convergent evolution on the other, have several implications for understanding brain evolution. First, similar abilities may be conferred by convergent rather than homologous circuits, even among closely related species. Furthermore, closely related species may use the same information in different ways, or they may use different means to obtain the same information. One reason that convergence is so common in the biological world may be that the evolutionary appearance of novel functions is associated with constraints, for example in the algorithms used for a given neural computation. Convergence in functional organization may thus reveal basic design features of neural circuits in species that possess unique evolutionary histories but use similar algorithms to solve basic computational problems.
Evolutionary Convergence and Shared Computational Principles in the Auditory System
Authors: Carr C.E. , Soares D.
Published: April 2003

Precise temporal coding is a hallmark of the auditory system. Selective pressures to improve accuracy or encode more rapid changes have produced a suite of convergent physiological and morphological features that contribute to temporal coding. Comparative studies of temporal coding also point to shared computational strategies, and suggest how selection acts to improve coding. Both the avian cochlear nucleus angularis and the mammalian cochlear nuclei have heterogeneous cell populations, and similar responses to sound. These shared characteristics may represent convergent responses to similar selective pressures to encode features of airborne sound.
Long-Term Effects of the Substituted Benzamide Derivative Amisulpride on Baseline and Stimulated Prolactin Levels
Authors: Schlösser R. , Gründer G. , Anghelescu I. , Hillert A. , Ewald-Gründer S. , Hiemke C. , Benkert O.
Published: April 2003

In the present study, we investigated the long-term effects of treatment with amisulpride, a substituted benzamide derivative, as compared with the effects of treatment with flupenthixol, a thioxanthene, on the prolactin levels in schizophrenic patients. After completing 6 weeks of medication with either amisulpride or flupenthixol, the patients entered a long-term maintenance treatment with amisulpride 200–600 mg/day or flupenthixol 5–15 mg/day for a maximum of 12 months with a subsequent drug-free follow-up until month 15. Eighteen initially included patients were still participating in the study at month 6. In the flupenthixol group, only 1 patient treated reached month 12, and none of the patients reached month 15. For the amisulpride treatment group, months 12 and 15 were completed by 9 and 6 patients, respectively. After 1, 3, 6, and 12 months of treatment, and finally 3 months after cessation of treatment, the basal and thyrotropin-releasing hormone-stimulated secretions of prolactin were investigated. The prolactin plasma levels were elevated in both treatment groups during the course of maintenance treatment with a maximum effect at month 1. Flupenthixol treatment initially raised the prolactin levels about two- or threefold, and a subsequent decline during months 3 and 6 occurred. However, only the changes for month 1 reached the level of a statistical trend. The prolactin secretion was initially increased over tenfold by amisulpride. The prolactin levels at months 1, 3, 6, and 12 were significantly elevated as compared with the baseline values. A continuous decline of prolactin levels in both treatment groups occurred over the course of the next months. The prolactin response after the thyrotropin-releasing hormone challenge was not significantly changed over the long-term course. Notably, in the amisulpride group, 3 months after cessation of treatment at month 12, the elevated levels of prolactin returned to baseline at month 15. In summary, amisulpride demonstrated more pronounced effects than flupenthixol on the prolactin levels. However, the findings indicate also that treatment with amisulpride at clinically effective doses can be achieved at significantly lower prolactin levels during the long-term maintenance phase than during the prior acute phase.
Comparison of Tracheal Aspirate and Bronchoalveolar Lavage Specimens from Premature Infants
Authors: D’Angio Carl T. , Basavegowda Kumar , Avissar Nelly E. , Finkelstein Jacob N. , Sinkin Robert A.
Published: April 2003

Lung fluid obtained by tracheal aspiration (TA) or bronchoalveolar lavage (BAL) has been used to study bronchopulmonary dysplasia (BPD). These two sample collection methods have seldom been compared. Paired BAL and TA specimens were collected 1, 3, 7 and 28 days after birth in 40 infants <34 weeks’ gestation during a randomized, controlled trial of dexamethasone for BPD prophylaxis. Interleukin 8 (IL-8) and cell counts were measured. Compared to subjects without BPD, those who developed BPD or died by 28 days had elevated IL-8 in epithelial lining fluid on day 1 in both BAL specimens (20 ng/ml vs. 2 ng/ml) and TA specimens (101 ng/ml vs. 18 ng/ml). IL-8 levels (r = 0.55) and neutrophil proportions (r = 0.51) were moderately correlated between BAL and TA samples. TA specimens may be suitable substitutes for BAL samples in some studies of newborn lung fluid.
Randomized, Double-Blind Study of Prulifloxacin versus Ciprofloxacin in Patients with Acute Exacerbations of Chronic Bronchitis
Authors: Grassi Carlo , Salvatori Enrica , Rosignoli Maria Teresa , Dionisio Paolo
Published: April 2003

Background: Recently the role of bacteria in acute exacerbations of chronic bronchitis (AECB) as well as antibiotic treatment with selected drugs, especially fluoroquinolones, have been better defined. Objective:To assess the efficacy and safety in patients with AECB of prulifloxacin in comparison with ciprofloxacin. Methods: AECB was defined according to the guidelines for the evaluation of new anti-infective drugs for the treatment of respiratory tract infections (1992). 235 patients took part in the trial; 117 (88 males and 29 females, mean age 64.8 years) received 600 mg prulifloxacin once daily and 118 (91 males and 27 females, mean age 64.5 years) 500 mg ciprofloxacin twice a day, for a duration of 10 days. The study design was randomized, multicenter, double-blind, double-dummy. Efficacy evaluations were performed by comparing pretreatment and posttreatment assessments. The clinical response was determined by 4-point rating scores on cough, dyspnea, and expectoration (volume and appearance). The microbiological response was assessed on sputum specimen. Results: Clinical success was observed in 84.7 and 85% of patients in the prulifloxacin and ciprofloxacin groups, respectively. The 95% confidence interval proved the equivalence of treatments. Both drugs successfully eradicated the most commonly isolated strains, including Haemophilus influenzae, Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa. Both treatments were well tolerated. Adverse drug reactions were always of mild or moderate intensity. Conclusion: The study showed that a 10-day course of prulifloxacin is as effective and safe as ciprofloxacin in the treatment of patients with AECB.
Automated Analysis of Data Is Inferior to Visual Analysis of Ambulatory Sleep Apnea Monitoring
Authors: Fietze Ingo , Glos Martin , Röttig Jens , Witt Christian
Published: April 2003

Background: Many ambulatory sleep apnea monitoring devices are equipped with software which allows an automated analysis of data as well as a visual analysis. Objective: The Merlin system which records heart rate, snoring sound, efforts, oronasal flow, body position and oxygen saturation was investigated to identify proper parameter settings for the automated analysis and to compare the automated with the visual analysis in patients with mild obstructive sleep apnea syndrome (OSAS). Sensitivity and specificity of the visual and automated analysis of ambulatory monitoring in comparison with visual polysomnographic (PSG) analysis were determined. Methods and Results: First, we tried to find the optimal parameters for the automated analysis, using 7 different settings in 17 OSAS patients. Furthermore, we applied the optimized setting to 66 OSAS patients who were admitted (age 50.9 ± 9.9 years, BMI 32.9 ± 5 kg/m2), and compared the results with the visual analysis of raw data. The patients slept for one night in the sleep laboratory with Merlin and PSG simultaneously to compare the visual and automated analysis of Merlin data with results from the visual analysis of PSG. Automated analysis leads to an underestimation of the respiratory disturbance index (RDI; p < 0.001) compared with both the visual analysis and results of PSG. Using a cutoff level of 5 apneas and hypopneas/h for the diagnosis of OSAS, the sensitivity of Merlin with the automated analysis is 40.6% and the specificity is 100%. With a cutoff level of 15/h, sensitivity and specificity rose to 91.3 and 100%, respectively, which is comparable to the visual analysis. Conclusion: Merlin is a reliable device for detection of sleep-related breathing disorders, but recordings should be analyzed visually, especially in patients with a low RDI.
Respiratory Failure due to Vocal Cord Paresis in Myasthenia gravis
Authors: Teramoto Koji , Kuwabara Masayoshi , Matsubara Yoshito
Published: April 2003

This report describes a female patient with myasthenia gravis who developed respiratory failure due to vocal cord paresis. The diagnosis was delayed due to the absence of other myasthenic symptoms (e.g. ptosis, muscle weakness and dysphagia). On direct laryngoscopy, her vocal cords were seen to be in the paramedian position and to move apart after the intravenous injection of edrophonium. The patient initially presented with ocular myasthenia and later returned with isolated respiratory failure. A review of the pertinent literature revealed few reports on myasthenia gravis presenting in this manner.
Enhanced Expression of Adhesion Molecules of the Retinal Vascular Endothelium in Spontaneous Diabetic Rats
Authors: Nozaki Miho , Ogura Yuichiro , Hirabayashi Yoshifumi , Saishin Yoshitsugu , Shimada Shoichi
Published: April 2003

Otsuka Long-Evans Tokushima Fatty (OLETF) rats are a spontaneously diabetic strain with clinical features resembling those of human noninsulin-dependent diabetes mellitus. These rats show increased leukocyte entrapment in the retina. The present study was designed to investigate the immunolocalization of intercellular adhesion molecules-1 (ICAM-1) and P-selectin in the retinas of OLETF rats. Four 72-week-old male OLETF rats and 4 age- and sex-matched Long-Evans Tokushima Otsuka (LETO) control rats were used. Western blot analysis and immunohistochemical study were performed using an anti-P-selectin monoclonal antibody (mAb) and an anti-ICAM-1 mAb. Western blot analysis showed increased expression of both ICAM-1 and P-selectin in the retinas of OLETF rats. Immunohistochemically, OLETF rats expressed greater amounts of ICAM-1 and P-selectin in the retinal vascular endothelium than did LETO rats. These findings demonstrated the upregulation of ICAM-1 and P-selectin in the retina of OLETF rats. The enhanced expression of these adhesion molecules might participate in the pathogenesis of early diabetic microangiopathy in the retina.
Serum Cholesterol and Leptin Levels in Patients with Borderline Personality Disorder
Authors: Atmaca Murad , Kuloglu Murat , Tezcan Ertan , Gecici Omer , Ustundag Bilal
Published: April 2003

The association between low or lowered cholesterol and impulsivity, aggressive behaviours and suicide remains controversial. In the present study, cholesterol and leptin levels of patients with borderline personality disorder in whom impulsivity, aggressive behaviours and suicide attempts are clearly established have been compared with those of healthy controls. The study group consisted of 16 patients with borderline personality disorder and 16 healthy controls. All patients were assessed with the Barratt Impulsivity Scale (BIS), Buss-Durkee Hostility Inventory (BDHI) and Hamilton Depression Rating Scale (HDRS). Fasting serum cholesterol and leptin levels were measured. The mean cholesterol and leptin levels of the patient group were significantly lower than those of the controls. Likewise, the patients with current suicidal thoughts and a history of suicide attempt had statistically significantly lower cholesterol and leptin levels compared with the patients without those features. There was an inverse correlation between both cholesterol and leptin levels, and impulsivity as determined by the BIS or aggression as determined by the BDHI, but no correlation between both cholesterol and leptin levels and the HDRS was found in the patients. In conclusion, the present study demonstrates that the patients with borderline personality disorder have lower cholesterol and leptin levels than healthy controls. Low serum cholesterol and leptin levels are associated with all dimensions of the disorder – impulsivity, aggression and suicidality – but are not associated with the presence and the severity of comorbid depression.
Glomerular Epithelial Cell Injury Accelerates the Progression of Antibody-Induced Mesangial Proliferative Nephritis
Authors: Shinosaki Toshihiro , Notoya Mitsuru , Nomura Yasuharu , Miyai Ikuko , Kobayashi Tatsuo , Kurihara Hidetake
Published: April 2003

Background: Anti-Thy-1.1 antibody induces mesangioproliferative glomerulonephritis; however, the mesangial lesion is spontaneously recovered to the normal feature. Glomerular epithelial cells (GECs) play a crucial role in the glomerular function. Very little is known about the involvement of GECs in this disease model. This study is designed to investigate whether GEC injury prolongs the mesangial lesion. Methods: The effects of GEC damage on mesangioproliferative nephritis were studied with combined treatment using puromycin aminonucleoside (PAN) and monoclonal antibody (MAb) against rat mesangial Thy-1.1. Urinary protein, BUN, Pcr and Ccr were measured. To clarify the underlying mechanisms, morphological study and immunohistochemistry for α-SMA, FGF-2 and PCNA were carried out. Results: Simultaneous administration of PAN plus MAb induced progressive mesangioproliferative nephritis compared to PAN or MAb alone. Rats with combined treatment displayed renal dysfunction with massive proteinuria. Morphological studies showed that the glomeruli in combined group had features resembling those of progressive mesangial proliferative glomerulonephritis in humans. Morphologic lesions of GECs in acute nephritic phase were severer than those in other groups. Immunohistochemistry revealed that glomeruli of combined treatment exhibited persistent overexpression of α-SMA and FGF-2. Conclusions: Simultaneous dysfunction of GECs and mesangial cells can lead to persistent glomerular perturbations with prolonged phenotypic change of mesangial cells, resulting in end-stage renal deficiency. GEC damage during the acute nephritic phase contributes to the progression of irreversible renal disease.
The Anti-Platelet Agent, Ticlopidine, Upregulates Interleukin-1-Beta-Stimulated Nitric Oxide Production in Cultured Rat Vascular Smooth Muscle Cells
Authors: Inoue Makoto , Kusano Eiji , Ito Chiharu , Akimoto Tetsu , Iimura Osamu , Nemoto Jun , Amemiya Morimasa , Muto Shigeaki , Asano Yasushi
Published: April 2003

Background: Hemodialysis patients who had been treated with anti-platelet aggregation drugs, including ticlopidine, sometimes developed hypotension. The mechanism by which ticlopidine lowers the blood pressure in hemodialysis patients is unclear. To elucidate the mechanism of the action of this drug, we investigated cytokine-stimulated nitric oxide (NO) metabolism by ticlopidine in cultured rat vascular smooth muscle cells (VSMC). Methods: Nitrite, a stable metabolite of NO, and intracellular cAMP and cGMP contents were assayed by the Griess method and enzyme immunoassay, respectively. iNOS mRNA and protein expressions were analyzed by Northern blotting and Western blotting. Results: Ticlopidine enhanced interleukin-1β (IL-1β)-induced nitrite production in a dose- and time-dependent manner. The mRNA and protein expressions of inducible NO synthase were upregulated by ticlopidine in a dose- and time-dependent manner. IL-1β alone stimulated both intracellular cAMP and cGMP contents, and the addition of ticlopidine further enhanced their contents. KT 5720, a selective inhibitor of protein kinase A, but not KT 5823, a selective inhibitor of protein kinase G, abolished the enhancement of IL-1β-induced nitrite production by ticlopidine. In addition, a phosphodiesterase inhibitor, isobutylmethylxanthine, enhanced IL-1β and ticlopidine induced nitrite production. Conclusion: We concluded that ticlopidine enhanced the IL-1β-induced NO production via cAMP and subsequent activation of protein kinase A in cultured rat VSMC.
Endovascular Therapy of Acute Vertebrobasilar Occlusion: Early Treatment Onset as the Most Important Factor
Authors: Eckert Bernd , Kucinski Thomas , Pfeiffer Gustav , Groden Christoph , Zeumer Herrmann
Published: April 2003

In view of the poor prognosis for patients with acute intracranial vertebrobasilar occlusion (VBO), factors were sought that predict survival and good neurologic outcome after acute endovascular treatment by means of local intra-arterial fibrinolysis (LIF) and percutaneous transluminal angioplasty (PTA). LIF was performed in 83 patients with angiographically established acute VBO. A significant residual stenosis after LIF was treated by additional PTA in 8 patients. The types of occlusion were classified as either embolic occlusion (EO) or atherothrombotic occlusion (AO). Outcome was evaluated after 3 months by the Barthel Index (BI) as favorable (BI >90), unfavorable (BI <90) or death and compared for each of 3 diagnostic or treatment variables: recanalization success, occlusion type and time to treatment. Four fibrinolytic treatment modes [urokinase, low-dose and high-dose recombinant tissue-type plasminogen activator (rt-PA), rt-PA + Lys-plasminogen] were also analyzed. The outcome was favorable in 19 patients (23%), unfavorable in 14 (17%) and 50 died (60%). Recanalization was successful in 54 patients (66%). The neurologic outcome was better in recanalized than in nonrecanalized patients (favorable outcome: 30 vs. 10%, mortality: 54 vs. 72%; p = 0.118). The neurologic outcome was better in EO than in AO (favorable outcome: 31 vs. 17%, mortality: 47 vs. 70%, p = 0.112). Under combined treatment by LIF and PTA in 8 patients with AO, 4 survived, 3 with a favorable outcome (38%). Early treatment onset (≤6 h) led to a significantly better neurologic outcome than delayed treatment onset (>6 h; favorable outcome: 36 vs. 7%, mortality: 52 vs. 70%, p = 0.005). Although no statistically significant differences were found between the types of fibrinolytic agents, treatment with rt-PA and Lys-plasminogen tended toward better results. Early treatment onset proved to be the most important factor for successful endovascular therapy in acute VBO, whereas recanalization and presence of an embolic occlusion also tended toward better results. Additional PTA may be a promising therapy in cases of significant residual stenosis after LIF.
Relation between Age and Number of Aneurysms in Patients with Subarachnoid Haemorrhage
Authors: Pleizier C. Machiel , Ruigrok Ynte M. , Rinkel Gabriël J.E.
Published: April 2003

Background: Because age and the presence of atherosclerosis are risk factors for the presence of aneurysms, the presence of multiple aneurysms may also increase with age. Familial preponderance is another risk factor for the presence of aneurysms. Familial subarachnoid haemorrhage (SAH) occurs at an earlier age than sporadic SAH, and a higher frequency of multiple aneurysms has been suggested in familial SAH. This may imply that the multiplicity of aneurysms is associated with younger age. We studied the relation between age and the number of aneurysms in patients with SAH. Methods: From our database we selected patients with aneurysmal SAH admitted between 1985 and 1999. Inclusion criteria were: (1) both carotid and vertebral arteries had been visualised; (2) at least one aneurysm was found, and (3) admission within 72 h after onset of symptoms. For the 555 patients included we recorded the age, sex and number of aneurysms. The patients were categorised into patients with a single aneurysm, patients with more than one aneurysm and those with more than two aneurysms. For all categories we calculated the proportion of patients younger than the median age and the differences between these proportions, with corresponding 95% confidence intervals (CI). We also calculated relative risks (RR) of multiple aneurysms for gender and age below the median. Results: 485 patients had a single aneurysm, and 70 patients had more than one aneurysm. The proportion of patients younger than the median age (51 years) with one aneurysm was 47.8%, for more than one aneurysm 61.4% (difference 13.6%; 95% CI 1.4–25.8), and for more than two aneurysms 82.6% (difference 34.8%, 95% CI 18.7–50.9). The RR of women for multiple aneurysms was 1.52 (95% CI 0.61–3.77), and that of age below the median 4.86 (95% CI 1.68–14.1). Conclusions: Patients with multiple aneurysms are younger than patients with a single aneurysm. This may suggest that atherosclerotic risk factors are less important than genetic factors in the development of multiple aneurysms.
Evolution of Human Intelligence: The Roles of Brain Size and Mental Construction
Authors: Gibson Kathleen R.
Published: April 2003

Two competing philosophical paradigms characterize approaches to the evolution of the human mind. One postulates continuity between animal and human behavioral capacities. The other assumes that humans and animals are separated by major qualitative behavioral and mental gaps. This paper presents a continuity model that suggests that expanded human mental capacities primarily reflect the increased information processing capacities of the enlarged human brain including the enlarged neocortex, cerebellum, and basal ganglia. These increased information processing capacities enhance human abilities to combine and recombine highly differentiated actions, perceptions, and concepts in order to construct larger, more complex, and highly variable behavioral units in a variety of behavioral domains including language, social intelligence, tool-making, and motor sequences. Environmental input, including self-generated input, interacts with mental constructional capacities to assure that developing humans acquire species-typical and culturally-specific behavioral patterns. This mental constructional model is compatible with our current understanding of differences between human and non-human primate brains, of human brain plasticity, and of the minimal genetic differences between humans and chimpanzees.
Psychological Diversity in Chimpanzees and Humans: New Longitudinal Assessments of Chimpanzees’ Understanding of Attention
Authors: Povinelli Daniel J. , Dunphy-Lelii Sarah , Reaux James E. , Mazza Michael P.
Published: April 2003

We present the results of 5 experiments that assessed 7 chimpanzees’ understanding of the visual experiences of others. The research was conducted when the animals were adolescents (7–8 years of age) and adults (12 years of age). The experiments examined their ability to recognize the equivalence between visual and tactile modes of gaining the attention of others (Exp. 1), their understanding that the vision of others can be impeded by opaque barriers (Exps. 2 and 5), and their ability to distinguish between postural cues which are and are not specifically relevant to visual attention (Exps. 3 and 4). The results suggest that although chimpanzees are excellent at exploiting the observable contingencies that exist between the facial and bodily postures of other agents on the one hand, and events in the world on the other, these animals may not construe others as possessing psychological states related to ‘seeing’ or ‘attention.’ Humans and chimpanzees share homologous suites of psychological systems that detect and process information about both the static and dynamic aspects of social life, but humans alone may possess systems which interpret behavior in terms of abstract, unobservable mental states such as seeing and attention.
Problem Solving as Model Refinement: Towards a Constructivist Epistemology
Authors: Luger George F. , Lewis Joseph , Stern Carl
Published: April 2003

In recent years the Artificial Intelligence research group at the University of New Mexico have considered several areas of problem solving in interesting and complex domains. These areas have ranged from the low level explorations of a robot tasked to explore, map, and use a new environment to the development of very sophisticated control algorithms for the optimal use of particle beam accelerators. Although the results of our research have been reflected in computer-based problem solvers, such as the robot discovering and mapping out its world, these computational tasks are in many ways similar to expert human performance in similar tasks. In fact, in many important ways our computer-based approach mimics human expert performance in such domains. This paper describes three of these task domains as well as the software algorithms that have achieved competent performances therein. We conclude this paper with some comments on how software models of a domain can elucidate aspects of intellectual performance within that context. Furthermore, we demonstrate how exploratory problem solving along with model refinement algorithms can support a constructivist epistemology.
Acoustic Modulation of Electrically Evoked Otoacoustic Emission in Chickens
Authors: Sun Wei , Chen Lin , Salvi Richard J.
Published: April 2003

Electrically evoked otoacoustic emissions (EEOAEs) can be elicited from the chicken inner ear. Since lesion studies implicate hair cells are the source of EEOAEs, we hypothesized that acoustic stimuli would modulate EEOAE amplitude at cochlear locations where the acoustic and electrical stimuli overlap. To assess this interaction, EEOAEs were measured as the frequency and amplitude of the acoustic stimuli were varied. EEOAEs, evoked by AC current (3–250 µA rms) delivered to the round window had a broad band pass response (1–6 kHz) with a peak between 3 and 4 kHz and maximum amplitude of 27 dB SPL. EEOAE suppression/enhancement tuning curves were measured at 2, 3, 4 and 6 kHz by varying the frequency of a 70 dB SPL tone and measuring the change in EEOAE amplitude. EEOAE tuning curves were characterized by a tip; a narrow range of frequencies where EEOAE amplitude was suppressed by as much as 5 dB, and by sidebands, a range of frequencies above and below the tip where EEOAE amplitude was enhanced by as much as 1.5 dB. The best suppression frequency, or characteristic frequency, was close to the frequency of the EEOAE elicited by the 3- or 4-kHz electric stimulus. However, the characteristic frequency was displaced towards higher frequencies for the 2-kHz electric stimulus, and towards lower frequencies for the 6-kHz electric stimulus. EEOAE suppression increased approximately linearly with acoustic level. These results suggest that EEOAEs evoked by round window stimulation are predominantly generated by hair cells near the 3- to 4-kHz region of the cochlea.
Nephrolithiasis at the Turn of the 18th to 19th Centuries: Biochemical Disturbances
Authors: Richet Gabriel
Published: April 2003

This report will discuss the relationship between urinary calculi, urine composition and urinary sediment and the link to chemistry unveiled during the years 1775–1840. It was by this interconnection that physicians, who were also chemists, introduced some basic sciences into medicine particularly in studying normal and diseased metabolism. The chemistry of urinary stones definitely influenced the progress of medicine in the post-Enlightment period. ‘We would probably still not have chemistry, botany, or anatomy had not physicians studied and taught them.’ G. Cuvier Report on Natural Sciences, Paris 1980.
Phase II Trial of Vinorelbine, Cisplatin and Continuous Infusion of 5-Fluorouracil Followed by Hyperfractionated Radiotherapy in Locally Advanced Head and Neck Cancer
Authors: Orecchia Roberto , Jereczek-Fossa Barbara A. , Catalano Gianpiero , Chiesa Fausto , De Pas Tommaso , Masci Giovanna , Krengli Marco , Vavassori Andrea , De Paoli Fiora , Robertson Chris , Marrocco Emanuela , De Braud Filippo
Published: April 2003

Objective: We undertook a prospective phase II study to assess the feasibility and activity of a new induction chemotherapy regimen followed by hyperfractionated irradiation in locally advanced squamous cell head and neck cancer. Methods: 25 patients with locally advanced head and neck cancer were treated with 4 cycles of vinorelbine (20 mg i.v. day 1, 3), cisplatin (60 mg/m2 i.v. day 1) and 5-fluorouracil (200 mg/m2 continuous i.v. infusion day 1–21) (ViFuP regimen) followed by bifractionated radiotherapy (bidRT) up to 74.4 Gy in 62 fractions of 1.2 Gy twice daily. Results: Chemotherapy was well tolerated, 6 patients developed grade 3 and one patient grade 4 neutropenia. Response to chemotherapy was observed in 19 patients (76%) including three complete responses and 16 partial responses. Planned bidRT was completed in 25 patients and all but one received planned bidRT dose without interruptions. Radiotherapy was well tolerated, mucositis was the most common side effect (grade 3–12 patients, grade 4–1 patient). At evaluation after the completion of bidRT, 13 patients had complete response (52%), 7 partial response (28%), 2 stable disease and 3 tumor progression. At the median follow-up of 18.2 months, 11 patients were alive and free of disease, and 14 patients had died (12 of tumor). Late xerostomy was observed in all but one 3-month survivors. Late mandibular necrosis was seen in 1 patient. Conclusions: bidRT preceded by ViFuP seems a feasible and active combination in locally advanced head and neck cancer. Good patient compliance did not compromise the delivery of planned dose of bidRT. However, short median duration of response (14.6 months) and moderate median overall survival (18.7 months) indicate the need for more intensive therapeutic strategies. On the basis of these results, modifications of our treatment schedule (shortening the overall treatment time by reduction of chemotherapy cycles and the use of chemotherapy concomitantly with irradiation) are planned for the future study.
Predicting Chemotherapy Response to Paclitaxel-Based Therapy in Advanced Non-Small-Cell Lung Cancer (Stage IIIb or IV) with a Higher T Stage (> T2)
Authors: Hsu Wu-Huei , Yen Ruoh-Fang , Kao Chia-Hung , Shiun Shih-Chih , Hsu Nan-Yung , Lin Cheng-Chieh , Lee Cheng-Chun
Published: April 2003

Objective: The aim of this study was to compare technetium-99m methoxyisobutylisonitrile (Tc-MIBI) chest single photon emission computed tomography (SPECT) results, immunohistochemical analyses of P-glycoprotein (Pgp) expression and response to paclitaxel in non-small-cell lung cancer (NSCLC). Methods: Before chemotherapy with paclitaxel, 30 patients with stage IIIb or IV NSCLC were enrolled in this study. Early chest SPECT was performed 10 min after intravenous injection of Tc-MIBI. Tc-MIBI chest SPECT images were qualitatively interpreted. Early tumor-to-normal lung ratios (T/NL) were calculated quantitatively. Immunohistochemical analyses were performed on multiple nonconsecutive sections of the biopsy specimens to determine Pgp expression. Chemotherapy response was evaluated in the third month after completion of treatment by clinical and radiological methods. Results: All 15 (100%) cases with good response and negative Pgp expression had positive results of early Tc-MIBI chest SPECT. Ten of 15 (67%) cases with poor response and positive Pgp expression had negative results of early Tc-MIBI chest SPECT. These early T/NL ratios (3.3 ± 0.8 for the 15 patients with good response and 2.0 ± 0.2 for the 5 patients with poor response) in lung cancer could be detected on early Tc-MIBI chest SPECT. The difference was significant (p < 0.05) by an independent Student t test. However, no significant differences were found for other prognostic factors (age, sex, body weight loss, performance status, tumor cell type, and tumor stage) between the good and poor response groups. Conclusion: Early Tc-MIBI chest SPECT can be used to understand the Pgp expression in NSCLC and to quickly predict chemotherapy response to paclitaxel.