bluuebunny/crossref_metadata_2025 huggingface dataset:
Mean Platelet Volume and Coronary Heart Disease in Hemodialysis Patients
Authors: Henning Bernard F. , Zidek Walter , Linder Bertolt , Tepel Martin
Published: April 2003

Background: Mean platelet volume (MPV) has been shown to be an independent risk factor for myocardial infarction in the general population. Methods: In the present cross-sectional study it was examined whether MPV may be associated with coronary heart disease (CHD) in patients in chronic hemodialysis treatment (n = 518). CHD was diagnosed if there was a history of myocardial infarction, coronary artery bypass grafting, or critical stenosis on coronary angiography. Results: Mean platelet volume in hemodialysis patients was 8.22 ± 0.06 fl. As compared with hemodialysis patients with a MPV <7.168 fl (the lower quintile limit), significantly more hemodialysis patients with a MPV >9.172 fl (the upper quintile limit) had CHD (odds ratio, 1.29; 95% confidence interval, 1.02–1.64). In a stepwise multiple logistic regression analysis MPV appeared to be an independent factor of CHD together with age, smoking, predialysis systolic blood pressure and serum triglyceride concentration. In a stepwise multiple linear regression model, MPV significantly depended on platelet count, volume of ultrafiltrate removed in one hemodialysis session, white blood cell count, treatment with beta blockers, heart rate, serum sodium and serum potassium concentrations. Additional measurements in 30 patients showed that MPV after a single hemodialysis session was not significantly different compared to predialysis values. Conclusion: From the present study it is concluded that MPV may be associated with CHD in hemodialysis patients.
Morphological Characteristics of the Cells in the Subcallosal Zone (Nucleus septohippocampalis) of the Human Fetus
Authors: Kostović Ivica , Rašin Mladen-Roko , Petanjek Zdravko , Judaš Miloš
Published: April 2003

Background/Objectives: Previous developmental studies pointed out the complexity of morphogenetic events in the interhemispheric cerebral wall during the formation of the corpus callosum. However, the changes in the morphology of individual cells in the region of the developing dorsal allocortex have not been studied. The aim of this study was to analyze the morphology and maturational changes of different cell classes in the subcallosal zone of the human fetal brain (22 and 28 weeks post ovulation), using Golgi and acetylcholinesterase staining. Results: The subcallosal zone occupies a paramedian territory situated between the developing corpus callosum (dorsally) and bundles of the fornix (ventrally). The two main findings are: (1) the presence of characteristic, area-specific cells, and (2) the presence of differences in the cellular composition between the medial and lateral portion of the subcallosal zone. The area-specific cells are neuron-like with a number of long and wavy (zigzag) processes, preferentially oriented towards the corpus callosum. The other types of cells include large glia-like cells, maturing neurons, migratory-like neurons, and radial glial cells. Conclusions: The midline portion of this subcallosal region is the part of the septohippocampal continuum and corresponds to the nucleus septohippocampalis of classic authors. The lateral (left and right paramedian) portions of the subcallosal region contain radial glial cells, and continue directly into the subventricular zone of the dorsal neocortical telencephalic wall. We therefore consider these paramedian subcallosal zones as a dorsal allocortical counterpart of the subventricular zone. Significantly decreased numbers of subcallosal cells in the adult brain suggest that the majority of neuronal and glial elements of the subcallosal region in the fetal brain are of a transient nature. The complexity and preferential orientation of glia-like and neuron-like subcallosal cells suggest that they may be involved in the guidance of callosal axons, whereas the cells of the septohippocampal continuum may have a pivotal role in the bidirectional growth of fornix system fibers.
A Model of Pulsations in Communicating Hydrocephalus
Authors: Egnor Michael , Zheng Lili , Rosiello Arthur , Gutman Fred , Davis Raphael
Published: April 2003

The traditional theory of communicating hydrocephalus has implicated the bulk flow component of CSF motion; that is, hydrocephalus is generally understood as an imbalance between CSF formation and absorption. The theory that the cause of communicating hydrocephalus is malabsorption of CSF at the arachnoid villi is not substantiated by experimental evidence or by physical reasoning. Flow-sensitive MRI has shown that nearly all CSF motion is pulsatile, and there is substantial evidence that hyperdynamic choroid plexus pulsations are necessary and sufficient for ventricular dilation in communicating hydrocephalus. We have developed a model of intracranial pulsations based on the analogy between the pulsatile motion of electrons in an electrical circuit and the pulsatile motion of blood and CSF in the cranium. Increased impedance to the flow of CSF pulsations in the subarachnoid space redistributes the flow of pulsations into the ventricular CSF and into the capillary and venous circulation. The salient features of communicating hydrocephalus, such as ventricular dilation, intracranial pressure waves, narrowing of the CSF-venous pressure gradient, diminished cerebral blood flow, elevated resistive index and malabsorption of CSF, emerge naturally from the model. We propose that communicating hydrocephalus is the result of a redistribution of CSF pulsations in the cranium.
Discernment of Adipose versus Nervous Tissue: A Novel Adjunct Solution in Lipomyelomeningocele Surgery
Authors: Patwardhan Ravish V. , Tubbs R. Shane , Leonard Robert J. , Kelly David , Killingsworth Cheryl R. , Rollins Dennis L. , Smith William M. , Ideker Raymond E. , Oakes W. Jerry
Published: April 2003

Objective: To determine a solution capable of discerning adipose versus nervous tissue, to aid in surgical separation of the adipose tissue which appears to be visually indistinguishable from nervous tissue in lipomyelomeningoceles (LMMs). Methods: The following solutes (in normal saline) were investigated, both at 25 and 37°C: beta-carotene, vitamin D, vitamin E, lecithin, hydrogen peroxide, lipase, protease, hyaluronidase, partially purified collagenase, purified collagenase, trypsin, trypsin plus purified collagenase and non-solute-containing saline (control). Each solution was applied to a pediatric lipoma to determine gross effects over a period of approximately 30 min. If a solution appeared to affect the adipose tissue grossly, studies of functional in vivo sensory evoked and spontaneous potentials using that particular solution were conducted upon sheep spinal cord, nerve roots, dura and peripheral nerve. Additionally, histological studies were conducted to determine the effect of that solution upon adipose tissue, spinal cord, myelin, dura and nerve roots. Results: Of all solutions investigated, partially purified collagenase type 1 (T1C; Lot M0M4322, Code CLS-1, Worthington Biochemical Corporation, Lakewood, N.J., USA) at 37°C was the most successful in grossly altering the consistency and appearance of adipose tissue. This change was more apparent over 20–30 min following application of the solution to the adipose tissue. Solutions not containing T1C did not show appreciable results; purified collagenase plus trypsin did not appear comparable or superior to T1C. No significant histological or functional change was noted when comparing the spinal cord, nerve rootlets, myelin, dura or peripheral nerve from the T1C-treated group versus normal (untreated) control groups. Conclusion: T1C appears to be a potentially effective solution for application during LMM surgery in the acute setting, and such use of an adjunct solution may significantly aid in the safe surgical resection of LMMs. Pending further research, this technique may be applied for other indications which require discernment or alteration of adipose versus nervous tissue.
Local Skin Lesions in the Rat after Subcutaneous Deposition of Capsaicin
Authors: Wallengren Joanna , Chen Duan
Published: April 2003

Capsaicin is used to investigate the role of peripheral sensory nerve fibers. In previous studies of rats treated by injection of capsaicin into the skin of the neck, ‘spontaneous’ lesions in the head and neck region were observed. In this study, the course of development over time, the regional distribution and the innervation of capsaicin-induced dermal lesions were assessed in young male Sprague-Dawley rats. In one experiment, capsaicin was administered subcutaneously by injection in the skin of the neck. In a second experiment, capsaicin was injected in the back by a long needle that tunneled under the skin and allowed the capsaicin to be deposited in the subcutaneous fat of the neck. The density and the distribution of dermal nerve fibers were investigated by immunohistochemistry, using antisera against a panneuronal marker, protein gene product 9.5 (PGP), and calcitonin gene-related peptide (CGRP). In the first experiment, rats developed lesions in the neck area 11 days after injection. In the second experiment, lesions appeared in the skin of the back and occasionally in the neck area 10 days after injection. Development of lesions in the afflicted areas was paralleled by local reduction in the density of CGRP-immunoreactive (IR) nerve fibers, 80% in the first experiment and 72% in the second. The number of PGP-IR fibers was likewise reduced, by 39 and 41%, respectively. The density of the CGRP-IR fibers in the wound area was the same as in the adjacent, nonlesioned skin. The healing of the capsaicin-induced lesions was slow compared with surgical wounds in control animals. The wounds healed with hypertrophic scars. The healing process in the skin of the back was associated with the proliferation of CGRP-IR fibers. The study shows cutaneous lesions to appear in the region of the subcutaneous deposition of capsaicin. A uniform depletion of capsaicin-sensitive nerve fibers in the area of deposition suggests that an additional factor is needed to induce lesions. Possibly, impaired nociception in the afflicted area results in more vigorous grooming behavior and this, in turn, in a local skin damage.
Novel Insights into Uremic Vascular Calcification: Role of Matrix Gla Protein and Alpha-2-Heremans Schmid Glycoprotein/Fetuin
Authors: Ketteler Markus , Vermeer Cees , Wanner Christoph , Westenfeld Ralf , Jahnen-Dechent Willi , Floege Jürgen
Published: April 2003

Cardiovascular mortality is markedly increased in the dialysis population when compared to non-uremic subjects. Vascular and valvular calcifications are most frequently found in dialysis patients at risk and are independent predictors of cardiovascular death in this population. Traditionally, the presence of hyperphosphatemia and an increased calcium × phosphate product was considered a major pathomechanistic condition leading to excessive vascular and soft-tissue calcifications in uremic subjects. Recent studies in knockout mice, however, revealed that deficiencies in calcium-regulatory proteins may also directly contribute to the development of extraosseus calcifications. α2-Heremans Schmid glycoprotein and matrix Gla protein are important inhibitors of calcification in vivo and there is novel evidence available that a deficiency in such proteins is involved in the pathogenesis of cardiovascular calcifications in dialysis patients.
Relationship between Salt Intake, Nitric Oxide and Asymmetric Dimethylarginine and Its Relevance to Patients with End-Stage Renal Disease
Authors: Osanai Tomohiro , Fujiwara Naoto , Saitoh Masayuki , Sasaki Satoko , Tomita Hirofumi , Nakamura Masayuki , Osawa Hiroshi , Yamabe Hideaki , Okumura Ken
Published: April 2003

Patients with essential hypertension (n = 24) were administered a low-salt diet (2 g NaCl/day), a high-salt diet (20–23 g) and then a low-salt diet for 7 days, and plasma levels of nitrate and nitrite (NOx) and asymmetric dimethylarginine (ADMA) were examined. There was a negative correlation between the percent changes in mean blood pressure and the plasma NOx concentration after salt loading and restriction. The percent change in plasma ADMA concentration was negatively correlated with that in the plasma NOx concentration after salt loading and restriction. In patients with end-stage renal disease (n = 51), the plasma ADMA concentration was positively correlated with the duration of dialysis treatment. The frequency of cardiovascular events was greater in patients with a plasma ADMA level of ≥3 µM than in those with a plasma AMDA level of <3 µM. The results indicate that ADMA is not only a modulator of salt sensitivity in hypertension but also a cardiovascular risk factor in end-stage renal disease.
Convergent Evolution on the Molecular Level
Authors: Zakon Harold H.
Published: April 2003

Divergence and convergence are two evolutionary processes by which organisms become adapted to their environments. With the advent of molecular biological techniques it is possible to ask if these processes are observed at the molecular level. There are many examples of molecular divergence in which molecular sequence or function change over evolutionary time. There are fewer reports of convergent evolution on the molecular level, and these claims are sometimes controversial. In this paper I discuss the types of convergent molecular evolution, describe the criteria for accepting or rejecting convergence, and give some examples relevant to neurobiology where convergence has been claimed. These include convergent evolution of opsins, gap junction proteins, neurotransmitter receptors, ion channels, and venoms directed against ion channels.
Why Are Olfactory Systems of Different Animals So Similar?
Authors: Eisthen Heather L.
Published: April 2003

As we learn more about the neurobiology of olfaction, it is becoming increasingly clear that olfactory systems of animals in disparate phyla possess many striking features in common. Why? Do these features provide clues about the ways the nervous system processes olfactory information? This might be the case if these commonalities are convergent adaptations that serve similar functions, but similar features can be present in disparate animals for other reasons. For example, similar features may be present because of inheritance from a common ancestor (homology), may represent responses to similar constraints, or may be superficial or reflect strategies used by researchers studying the system. In this paper, I examine four examples of features of olfactory systems in members of different phyla: the presence of odorant binding proteins in the fluid overlying olfactory receptor neurons; the use of G protein-coupled receptors as odorant receptors; the use of a two-step pathway in the transduction of odorant signals; and the presence of glomerular neuropils in the first central target of the axons of olfactory receptor cells. I analyze data from nematodes, arthropods, molluscs, and vertebrates to investigate the phylogenetic distribution of these features, and to try to explain the presence of these features in disparate animals. Phylogenetic analyses indicate that these features are not homologous across phyla. Although these features are often interpreted as convergent adaptations, I find that alternative explanations are difficult to dismiss. In many cases, it seems that olfactory system features that are similar across phyla may reflect both responses to similar constraints and adaptations for similar tasks.
Evaluation of Adolescent Statural Growth in Health and Disease: Reliability of Assessment from Height Measurement Series and Development of an Automated Algorithm
Authors: Coste Joël , Ecosse Emmanuel , Lesage Catherine , Chaussain Jean-Louis , Carel Jean-Claude
Published: April 2003

Objectives: The precise evaluation of adolescent growth spurt is necessary for numerous clinical research studies of growth disorders and treatments. The objectives of our study were: (1) to evaluate the reliability of clinicians’ ‘manual’ evaluation of the adolescent growth spurt from a collected series of height data, and (2) to construct an automated algorithm to determine the duration of the two phases of growth in health and disease (spurt and final slow growth) independent of clinical pubertal stages. Methods: One hundred and seventy-four growth curves of normally growing, GH-deficient and Turner’s syndrome subjects were presented twice to 2 experienced clinicians. Disagreement between evaluations and clinicians were settled to obtain a ‘consensual gold standard’ evaluation versus which the algorithm was assessed. Kappa statistics and Bland-Altman analyses were used to evaluate the reliability and agreement of the evaluations. Results: The reliability of ‘manual’ evaluation of adolescent growth spurt from collected series of height data appeared to be poor. Conversely, the developed algorithm is perfectly reliable and satisfactorily valid. Discrepancies with the clinical consensual gold standard were always fewer than the discrepancies between the expert clinicians, and were observed in similarly difficult curves. Conclusion: The developed algorithm may be useful for diverse clinical and biological research applications in children with growth disorders. This study also confirms the value of a comprehensive investigation of growth during adolescence independent of clinical staging.
Spontaneous Nocturnal Leptin Secretion in Children with Myelomeningocele and Growth Hormone Deficiency
Authors: Trollmann R. , Dörr H.G. , Gröschl M. , Blum W.F. , Rascher W. , Dötsch J.
Published: April 2003

Objective: To examine the spontaneous leptin secretion in patients with myelomeningocele (MMC) and growth hormone deficiency (GHD). Methods: Serum leptin levels were studied in 10 prepubertal MMC patients with GHD (CA 6.2 ± 0.5 years), 10 patients with idiopathic GHD (IGHD; CA 7.6 ± 0.7 years) and 12 children with normal variant short stature (NVSS; CA 7.6 ± 0.5 years). Mean BMI (kg/m2) values of the groups did not differ significantly. Nocturnal leptin levels were analyzed over 10 h (blood samples every 20 min) and measured by specific radioimmunoassay. Results: Mean leptin concentrations did not correlate with BMI in MMC patients. Nocturnal leptin secretion of MMC patients was significantly different to those of children with IGHD and NVSS. Morning leptin levels did not decline as observed in both other groups. Conclusion: Since all groups were matched for BMI values, we suggest a hypothalamic dysregulation of leptin secretion in MMC patients.
Measurement of Laminins in the Cerebrospinal Fluid Obtained from Patients with Alzheimer’s Disease and Vascular Dementia Using a Modified Enzyme-Linked Immunosorbent Assay
Authors: Matsuda Kazunori , Tashiro Ken-ichiro , Hayashi Yoshihito , Monji Akira , Yoshida Ichiro , Mitsuyama Yoshio
Published: April 2003

We developed a new enzyme-linked immunosorbent assay (ELISA) system using antibodies against intact human laminin, laminin α5-chain, laminin β1-chain, laminin γ1-chain and laminin α1-chain peptide (YFQRYLI). Using this ELISA, we measured the anti-laminin immunoreactivity levels in the cerebrospinal fluid (CSF) obtained from patients with Alzheimer’s disease (AD), vascular dementia (VaD), and other disorders. The present study showed the levels of certain laminins in CSF to demonstrate significant differences in the chain levels in different dementias. The AD group showed a significantly lower level of anti-laminin γ1 immunoreactivity. The late-onset AD group showed significantly elevated anti-laminin α1-peptide (YFQRYLI) immunoreactivity levels in comparison with the early-onset AD group and controls. On the other hand, the VaD group showed significantly higher levels of anti-intact human laminin and anti-laminin β1 immunoreactivity. The assays of anti-laminin immunoreactivity levels in CSF provided an efficient sensitivity (85.0%) and specificity (93.7%) for the diagnosis of AD by using the ratio of tau to anti-intact human laminin immunoreactivity levels. These results suggest that CSF laminin or its derivatives may correlate with the pathogenesis of AD and VaD, and the prevention of the proteolytic activity may be an effective therapeutic method for either preventing or slowing down the progression of AD. Furthermore, it was shown that performing ELISA for CSF laminins may prove to be useful for detecting the biological markers of AD and VaD.
Interleukin 1 Alpha Gene Polymorphism as a Susceptibility Factor in Alzheimer’s Disease and Its Influence on the Extent of Histopathological Hallmark Lesions of Alzheimer’s Disease
Authors: Pirskanen Mia , Hiltunen Mikko , Mannermaa Arto , Iivonen Susan , Helisalmi Seppo , Lehtovirta Maarit , Koivisto Anne Maria , Laakso Markku , Soininen Hilkka , Alafuzoff Irina
Published: April 2003

We investigated the association of the interleukin 1α (IL1A) (–889) C/T polymorphism with Alzheimer’s disease (AD) and with the extent of AD histopathological lesions, the senile/neuritic plaques (SPs/NPs) and neurofibrillary tangles. We evaluated 98 neuropathologically confirmed AD patients and 240 controls as well as 146 clinically diagnosed AD patients and 278 controls but found no association of the IL1A C/T polymorphism with AD even after adjustment for the apolipoprotein E (APOE) genotype, gender or age. The extents of AD histopathological lesions were not influenced by the IL1A genotype except after exclusion of the APOE Ε4 allele, when a trend towards more SPs/NPs was observed in AD patients with the IL1A C/C compared to patients with the T/T genotype. These results do not confirm previous studies which have indicated that the IL1A C/T polymorphism is a susceptibility factor for AD. However, the IL1A C/C genotype might be associated with the progression of SPs/NPs in AD patients, but the effect is weak and obscured by the APOE Ε4 allele.
Plasma Levels of Aβ42 and Aβ40 in Alzheimer Patients during Treatment with the Acetylcholinesterase Inhibitor Tacrine
Authors: Basun Hans , Nilsberth Camilla , Eckman Christopher , Lannfelt Lars , Younkin Steven
Published: April 2003

Deregulation of amyloid precursor protein (APP) processing with increased production of amyloid β-peptide (Aβ) is considered to be a key pathogenic event in Alzheimer’s disease (AD). It has been suggested that stimulation of the muscarinic M1 receptor subtype affects APP processing and leads to a change in Aβ concentration. To test the hypothesis that treatment with a cholinesterase inhibitor could change the levels of Aβ in plasma, we measured Aβ42 and Aβ40 plasma levels in AD subjects before tacrine treatment and at weeks 2 and 6 of treatment. Treatment with tacrine had no statistically significant effect on plasma Aβ42 and Aβ40 either at 2 weeks or at 6 weeks of administration compared to baseline levels. Plasma Aβ42 and Aβ40 levels showed large subject-to-subject variation but small variation within the same patient over the 3-sample interval. After 2 weeks of treatment with tacrine, there was a strong negative correlation between tacrine concentration and levels of Aβ42 (r = –0.64; p = 0.01) and Aβ40 (r = –0.55; p = 0.04). However, after 6 weeks there was no correlation between plasma concentrations of tacrine and Aβ42 (r = 0.33; p = 0.34) or Aβ40 (r = –0.22; p = 0.54) levels in plasma. After 2 weeks of treatment with an acetylcholinesterase inhibitor, we found a correlation between higher drug concentrations and lower β-amyloid levels. This might indicate an effect on APP metabolism with an increased α-cleavage. But after 6 weeks of drug treatment, there was no obvious drug effect on β-amyloid concentrations. This finding may indicate that compensatory mechanisms have started at 6 weeks and that no long-term effect on key pathological features in AD is to be expected by an inhibition of acetylcholinesterase.
Cerebral Amyloid Angiopathy, White Matter Lesions and Alzheimer Encephalopathy – A Histopathological Assessment
Authors: Haglund Mattias , Englund Elisabet
Published: April 2003

To test the hypothesis that the cerebral amyloid angiopathy (CAA) of Alzheimer’s disease (AD) is quantitatively associated with white matter lesions (WML), the brains of 63 demented patients exhibiting varying degrees of Alzheimer encephalopathy (AE) were examined, along with those of 10 nondemented control cases. The ratio of amyloid-positive to amyloid-negative vessels in the leptomeninges of the frontal pole from each patient was calculated subsequent to microscopical examination, and the severity of WML was graded according to previously published criteria. In AD cases without a significant component of vascular dementia, the level of CAA was found to correlate with the degree of WML diagnosed and graded by neuropathology. Neither age nor severity of AE correlated significantly with WML. There may be several reasons for the conflicting results of this study vis-à-vis earlier investigations; the roles played by different methods of staining, CAA quantitation and patient subgroup selection are also discussed.
Diagnosis and Severity of Asthma in the Elderly: Results of a Large Survey in 1,485 Asthmatics Recruited by Lung Specialists
Authors: Zureik Mahmoud , Orehek Jean
Published: April 2003

Background: Despite its high prevalence, epidemiological surveys on the diagnosis and severity of asthma in the elderly are seldom. Objective: The objectives of our study were: (i) to describe the criteria, used by French lung physicians, for the diagnosis of asthma in the elderly (age ≧ 65 years); (2) to investigate whether the age at the onset of asthma is related to the severity of asthma in the elderly. Methods: 1,485 asthmatics (783 men and 702 women; mean age ± SD = 73.2 ± 6.0 years) were included in this descriptive survey. They were recruited by 379 lung specialists who filled in standardized questionnaire. Results: 56% of men and 10% of women (p < 0.001) were smokers or ex-smokers FEV1/VC was significantly lower in men than in women (60.6 ± 16.1 versus 66.1 ± 16.9%; p < 0.001). Diagnostic criteria of asthma were both clinical and functional in 89% of cases. Bronchospasm reversibility was tested with inhaled β2-agonists (89%) and/or oral corticotherapy (36%). Asthma had been diagnosed before the age of 20 years in 10.4% of the patients, between 20 and 50 years in 28.3%, between 51 and 65 years in 38.1%, and after the age of 65 years in 23.2%. Higher FEV1 % of theoretical values and higher FEV1/VC were observed in subjects with late-onset asthma. The mean of FEV1 % of theoretical values was 58.1 ± 19.5% in subjects with asthma diagnosis before the age of 20 years, 60.5 ± 20.4% in those with asthma diagnosis between the age of 20 and 50 years, 62.5 ± 19.4% in those with asthma diagnosis between the age of 50 and 65 years, and 67.1 ± 21.4% in those with asthma diagnosis after the age of 65 years (p < 0.001). The mean number of drugs taken was significantly lower (2.2 ± 0.4) in late-onset asthma than in early-onset asthma (2.8 ± 0.1; p < 0.001). Conclusions: This study suggests that the severity of asthma may depend on age at the onset of symptoms and diagnosis. Early diagnosis and treatment may prevent the adverse consequences of persistent asthma.
Pulmonary Emboli Caused by Iliac Compression Syndrome without Leg Symptoms
Authors: Kishi Kazuma , Homma Sakae , Kawabata Masateru , Tsuboi Eiyasu , Narui Koji , Nakatani Tatsuo , Nakata Koichiro
Published: April 2003

Iliac compression syndrome is a clinical condition that occurs as a result of compression of the left common iliac vein by the overlying right common iliac artery. This syndrome most often affects young to middle-aged women, and patients usually have left leg symptoms. We report the unusual case of an 18-year-old male who had pulmonary emboli caused by iliac compression syndrome without leg symptoms. Combined venography and aortography confirmed the diagnosis. The patient was successfully treated with anticoagulants and vena cava filter insertion. Iliac compression syndrome should be considered when pulmonary embolism appears without obvious cause.
Treatment Approaches to Major Depressive Disorder Relapse
Authors: Schmidt Mark E. , Fava Maurizio , Zhang Shuyu , Gonzales Jill , Raute Nancy J. , Judge Rajinder
Published: April 2003

Objective: Although continuing antidepressant treatment after patients have responded to medication has been shown to greatly reduce the risk of relapse, this risk is not eliminated. A number of theories have been proposed to account for this apparent loss of efficacy. A common initial approach to managing relapse is to increase the dose of antidepressant. We prospectively evaluated the likelihood of response to increasing the fluoxetine doses in patients relapsing during a long-term efficacy study of two fluoxetine dosing regimens. Method: Patients meeting the DSM-IV criteria for major depressive disorder with modified HAMD17 scores ≧18 and CGI-severity scores ≧4 were treated for 13 weeks with open-label 20 mg/day fluoxetine in a multicenter US study. Responders (n = 501) were randomized to 20 mg fluoxetine daily, placebo, or 90 mg enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. If the patients relapsed during the continuation phase, they were offered a 25-week optional rescue treatment phase during which the study medication dose was increased as follows: (1) patients on placebo had treatment with fluoxetine 20 mg/day reinitiated, (2) patients on fluoxetine 20 mg/day had their dose increased to 40 mg/day, and (3) patients on a 90-mg weekly dose had their dose increased to 90 mg twice a week. The results of the rescue phase for the latter two groups who relapsed while on continuation treatment with fluoxetine are reported. Response was defined as a 50% reduction in the modified HAMD17 score since time of relapse and a CGI-severity score ≤2. Additional efficacy analyses included HAMD and CGI-severity changes from baseline to endpoint. Safety measures included assessment of treatment-emergent adverse events, vital signs, and laboratory measures. Results: Overall, patients relapsing during the continuation treatment responded to an increased dose (57% of the 40-mg-daily group and 72% of the enteric-coated 90-mg-twice-weekly group). Mean modified HAMD17 scores decreased from a mean of approximately 20 to below 8 and were maintained for up to 6 months in the responders. Thirty-five percent of patients either did not respond or initially responded but again relapsed after augmentation of medication. Conclusions: The patients relapsing after initially responding to fluoxetine can benefit from an increase in fluoxetine dose. These results also generally support increasing dose as a first-line treatment strategy for a patient who has relapsed while taking a previously effective dose of an antidepressant. Increasing enteric-coated fluoxetine 90 mg once weekly to twice weekly appeared to be as well-tolerated and effective in restoring response as increasing a daily fluoxetine dose from 20 to 40 mg.
Dropout from Brief Psychotherapy in Anorexia nervosa
Authors: Fassino S. , Abbate Daga G. , Pierò A. , Rovera G.G.
Published: April 2003

Background: Dropout from psychotherapy is an important issue that has received little systematic attention. This study investigated the phenomenon of dropout from brief psychotherapy for anorexia nervosa (AN). Methods: 99 outpatients suffering from AN of the restrictor type (n = 53) or binge/purging type (n = 46) were evaluated. Their clinical and personal characteristics were recorded, and body mass index was calculated for participants. They were administered the Eating Disorder Inventory-II (EDI-II), the State-Trait Anger Expression Inventory (STAXI) and the Temperament and Character Inventory (TCI). Results: Significant differences in some baseline psychopathologic (EDI-II, STAXI) and personality (TCI) variables emerged from the comparison between dropouts and completers. Patients who dropped out of the treatment showed higher levels of anger temperament, anger expression-in and expression-out and lower scores for the dimensions of character (low self-directedness and low cooperativeness). No differences were found between the two groups regarding sociodemographic and clinical variables. Conclusions: Dropout from brief psychotherapy seems to be related to either psychopathologic or personality aspects, such as the tendency to repress anger, which is encountered also in psychosomatic disorders, and the presence of more compromised dimensions of character, typical of subjects with personality disorders. This study of dropout from brief psychotherapy in AN provided interesting results that will need further confirmation. Possible implications for treatment are addressed.
Prevalence of Primary Cornea guttata and Morphology of Corneal Endothelium in Aging Japanese and Singaporean Subjects
Authors: Kitagawa Kazuko , Kojima Masami , Sasaki Hiroshi , Shui Ying-Bo , Chew Sek Jin , Cheng Hong-Ming , Ono Masaji , Morikawa Yuko , Sasaki Kazuyuki
Published: April 2003

The purpose of the present study was to examine, in the aging people, racial and gender differences in the morphology of corneal endothelium as well as the incidence of cornea guttata in two Asian subject groups, one in Singapore and the other in Japan. Four hundred and sixty-five Chinese Singaporeans and 299 Japanese subjects (residents of Monzen-machi, Ishikawa Prefecture) aged 50 years and older were recruited for the study. Corneal endothelial abnormalities were diagnosed with slit-lamp biomicroscopy and specular microscopy. Primary cornea guttata appeared as beaten metal appearance in slit-lamp images and dark regions in specular images. In addition to cornea guttata, corneal endothelial morphology was also analysed with specular microscopy. The mean cell density was 2,808/mm2 in the Japanese subjects which was significantly higher than the 2,718/mm2 seen in the Singaporeans (p < 0.001). The incidence of cornea guttata was significantly higher in the Singaporeans than in the Japanese individuals and also higher in women than in men of both racial groups. These differences support not only a racial and a gender factor but also a possible environmental influence.
Immunohistochemical Localization of Amino Acids in the Diabetic Retina of Goto-Kakizaki Rats
Authors: Takeo-Goto Shizuka , Doi Motoaki , Ma Ning , Goto Ryotaro , Semba Reiji , Uji Yukitaka
Published: April 2003

The Goto-Kakizaki (GK) rat is a spontaneous model of non-insulin-dependent diabetes mellitus without obesity and diabetic retinopathy. We examined the retinal distribution of L-glutamate, gamma aminobutyric acid (GABA), glycine, and L-aspartate as neurotransmitters in the GK rat retina, using an immunohistochemical method with high-affinity antibodies. The retinal structures in the GK rats were the same as the controls. However, in the GK rats, immunoreactivity of L-glutamate and GABA was observed in the Müller and photoreceptor cells in addition to the immunoreactivity in normal rats. There was no change in glycine distribution between GK rats and controls. In the GK rats, L-aspartate accumulated in the inner segment of the photoreceptor cells in addition to the normal distribution. We consider that these immunoreactivity patterns in the GK rat retina might be induced by ischemia associated with diabetes mellitus.
Renal Concentrating and Diluting Function in Deficiency of Specific Aquaporin Genes
Authors: Verkman A.S.
Published: April 2003

Aquaporins (AQP) are water-transporting proteins expressed in many fluid-transporting epithelia and endothelia. In kidney, AQP1 is expressed in plasma membranes of proximal tubule, thin descending limb of Henle and descending vasa recta, AQP2 in collecting duct luminal membrane, AQP3 and AQP4 in collecting duct basolateral membrane, AQP6 in intercalated cells, and AQP7 in the S3 segment of proximal tubule. Human mutations in AQP2 cause hereditary non-X-linked nephrogenic diabetes insipidus. Transgenic mice lacking the renal aquaporins have been useful in defining their role. Mice deficient in AQP1 are polyuric and unable to form a concentrated urine because of defective proximal tubule fluid absorption and countercurrent multiplication. Mice lacking AQP3 are markedly polyuric due to low water permeability across the cortical and outer medullary collecting duct. However, mice lacking AQP4, which is expressed mainly in inner medullary collecting duct, manifest only a mild defect in maximum urinary concentrating ability. The aquaporin null mice have normal urinary diluting ability. From many renal and extrarenal phenotype studies of aquaporin null mice, we conclude that aquaporins are important for rapid near-isosmolar transepithelial fluid absorption/secretion and for rapid vectorial water movement driven by osmotic gradients. The renal phenotype in aquaporin null mice suggests the utility of aquaporin blockers as novel aquaretic-diuretic agents.
Effect of Prolonged Uremia on Insulin-Like Growth Factor-I Receptor Autophosphorylation and Tyrosine Kinase Activity in Kidney and Muscle
Authors: Tsao Tanny , Fervenza Fernando , Friedlaender Michael , Chen Yu , Rabkin Ralph
Published: April 2003

Recently, based on a study in rats with chronic renal failure (CRF), it has been suggested that IGF-I resistance in uremia may be caused in part by defective IGF-I receptor autophosphorylation and tyrosine kinase activity. Thus if such a defect were to develop in prolonged acute renal failure (ARF), this may explain why IGF-I therapy, effective in rats, has failed to promote recovery from ARF in patients. Accordingly, we examined IGF-I receptor function in rats with uremia of increasing duration and in pair-fed sham-operated controls. After 6 days of prolonged ARF, kidney IGF-I receptor binding increased twofold, while IGF-I stimulated receptor phosphorylation and tyrosine kinase activity were unchanged. Muscle receptor binding, autophosphorylation and tyrosin kinase activity were similar to control values after 6 or even 21 days of uremia. Taking all these findings together it appears that IGF-I resistance in uremia cannot be attributed to a receptor defect. This in turn argues against altered receptor function as a cause of the failure of IGF-I to modify clinical ARF.
Ultrastructural Changes in the Cervical Epithelium during the Estrous Cycle of the Marsupial Monodelphis domestica (Grey Short-Tailed Opossum)
Authors: Wick Regula , Kress Annetrudi
Published: April 2003

Ultrastructural changes in the cervical epithelium related to the estrous cycle have been studied in the South American marsupial Monodelphis domestica. The two cervices protrude with prominent papillae into the sinus vaginalis. At times of simple columnar at others of more pseudostratified character consists of two types of cells, ciliated and secretory cells. The mucosal epithelium is uniform in its entire length and shows no division into an endo- and ectocervix. The mucosa of the cervix differs from the uterine endometrium. There are no glandular structures, but the luminal epithelium shows deep invaginations underlined by dense connective tissue. The most conspicuous changes include the height and the differentiation of the cervical epithelium which attains its maximum development during estrus, where secretory cells are fully packed with large secretory granules and ciliated cells are well developed. After extruding their granules, secretory cells may transform into ciliated cells, while ciliated cells show the phenomenon of deciliation in which cilia packets are shed into the cervical lumen. This transformation process takes place mainly during post- and metestrus. The presence of solitary cilia is only noticeable during pro-estrus, being in contrast to the uterine epithelium where they appear during the whole estrous cycle.
Swallowing and Stroke
Authors: Smithard David G.
Published: April 2003

The development of imaging techniques such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) scanning has allowed non-invasive imaging of the brain, to a greater detail, that in the past was not possible. These imaging modalities have allowed the study of the cortical control of swallowing both in the healthy volunteers and the stroke patient. It has become increasingly obvious that swallowing is complex and its recovery following stroke even more so. Swallowing is represented in many areas of the hemisphere and is affected in many different ways following stroke. In most, recovery is spontaneous, but in some it is slow or non-existent. Studies using direct and transcranial electrical stimulation and pharmacological agents have shown interesting results in the recovery of swallowing following stroke.
Effect of Riluzole on Cytosolic Ca2+ Increase in Human Osteosarcoma Cells
Authors: Jan Chung-Ren , Lu Yih-Chau , Jiann Bang-Ping , Chang Hong-Tai , Huang Jong-Khing
Published: April 2003

In human osteosarcoma MG63 cells, the effect of the neuroprotective drug riluzole on the intracellular Ca2+ concentration ([Ca2+]i) was measured using fura-2. Riluzole (50–500 µmol/l) caused a rapid and sustained plateau increase in [Ca2+]i in a concentration-dependent manner (EC50 = 150 µmol/l). The riluzole-induced rise in [Ca2+]i was prevented by 58 and 20% by extracellular Ca2+ removal and nifedipine, respectively, but was not changed by La3+ and verapamil. In Ca2+-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum (ER) Ca2+-ATPase, caused a monophasic increase in [Ca2+]i, after which the increasing effect of riluzole on [Ca2+]i was attenuated by 84%; also, pretreatment with riluzole abolished the thapsigargin-induced [Ca2+]i increase. U73122, an inhibitor of phospholipase C, abrogated the ATP (but not riluzole)-induced rise in [Ca2+]i. A low concentration (6 µmol/l) of riluzole selectively potentiated the bradykinin (but not ATP and histamine)-induced increase in [Ca2+]i. These results suggest that riluzole rapidly increases [Ca2+]i by stimulating both the extracellular Ca2+ influx via a nifedipine-sensitive pathway and intracellular Ca2+ release from the ER via an as yet unidentified mechanism(s).
Effects of Morphine on Oedema and Tissue Concentration of Nerve Growth Factor in Experimental Inflammation of the Rat Paw
Authors: Amann Rainer , Lanz Ilse , Schuligoi Rufina
Published: April 2003

Injection of carrageenan (1 mg) into the rat hind paw caused a time-dependent increase in paw volume that was maximal 3 h after injection. At this time, the concentration of nerve growth factor (NGF) in the skin of the inflamed paw was more than twofold higher than in the contralateral, non-inflamed paw. Treatment of rats with indomethacin reduced inflammatory oedema by 57%, morphine treatment attenuated oedema by 62%. While indomethacin had no statistically significant effect on the concentration of NGF in the skin of inflamed paws, morphine attenuated the NGF response by 24.2% in a naloxone reversible manner. These data suggest that drug-induced inhibition of inflammatory oedema is not predictive of its effect on an inflammation-induced rise in tissue NGF. Furthermore, our results confirm and extend previous observations suggesting an anti-inflammatory activity of morphine.
Small Cell Lung Cancer: Defining a Role for Emerging Platinum Drugs
Authors: Schiller Joan H.
Published: April 2003

Small cell lung cancer (SCLC) is characterized by early dissemination and a rapid, aggressive clinical course. It has, however, marked susceptibility to both chemotherapy and radiotherapy, although treatment is complicated by the fact that SCLC tumors invariably develop resistance to multiple chemotherapeutic agents. Local therapy is rarely of benefit in SCLC because three-quarters of patients present with metastatic disease and many of the remaining patients are thought to have micrometastatic disease. Chemotherapy is, therefore, the cornerstone of treatment. Of the many combination regimens used, etoposide/cisplatin or etoposide/carboplatin have emerged as the regimens of choice because they offer a good therapeutic index and can be combined with radiotherapy. Response to second-line therapy remains consistently poor. As the prototype platinum compound, cisplatin has played a major role in the management of SCLC. Although its exact contribution to the treatment of SCLC has been difficult to ascertain, a recent meta-analysis reported a significant 1-year survival advantage of approximately 4% with cisplatin-containing regimens versus regimens without. However, cisplatin is characterized by several serious adverse events and, like other chemotherapeutic agents, is eventually rendered ineffective against SCLC because of acquired resistance. Several new platinum formulations or compounds are showing promising activity in SCLC. The impetus for their development has been to circumvent cisplatin resistance or to improve upon the toxicity profile of cisplatin. If the early promise shown by these compounds is confirmed in the clinic, they may offer a new approach to the treatment of SCLC, including recurrent disease for which limited treatment options are currently available.
Expression of S100A6 and S100A4 in Matched Samples of Human Colorectal Mucosa, Primary Colorectal Adenocarcinomas and Liver Metastases
Authors: Komatsu Keiko , Murata Kohei , Kameyama Masao , Ayaki Masako , Mukai Mutsuko , Ishiguro Shingo , Miyoshi Jun , Tatsuta Masaharu , Inoue Masahiro , Nakamura Hiroyuki
Published: April 2003

Objective: S100A6 and S100A4, two of S100 protein family, have been suggested to be associated with cancer tumorigenesis and metastasis. The aim of this study was to evaluate the expression levels of S100A6 and S100A4 in matched samples of primary human colorectal adenocarcinomas (T), adjacent normal colorectal mucosa (N) and liver metastases (M). This gave us the advantage of directly comparing levels of S100A6 and S100A4 expression within the same genetic background. Methods: In matched samples of N, T and M from 10 colorectal adenocarcinoma patients, expressions of S100A6 and S100A4 were studied by Western blot and immunohistochemical analyses using specific antibodies against each protein. Results: The expression levels of S100A6 were significantly higher in T than in N (p < 0.05), while those of S100A4 showed no difference between T and N. There were no significant differences in the expression levels of S100A6 or S100A4 between M and T. Similar results were obtained by immunohistochemical analysis. Moreover, S100A6 was stained more intensely in invading fronts than in central portions of both T and M. Conclusions: The observed differential expression of S100A6 and S100A4 suggests that S100A6, rather than S100A4, is associated with human colorectal adenocarcinoma tumorigenesis and invasion/metastasis.
Family History, Life Events and the Factorial Structure of Depression in a Nigerian Sample of Inpatients
Authors: Ohaeri Jude U. , Otote David I.
Published: April 2003

The aims of the study were to examine the frequency of a family history of depression among 96 patients with subtypes of ICD-10 depression, their life event scores, and compare the factors of depression with other studies. Subjects were assessed using the PSE-9, 23-item HDRS, BPRS and life event schedule. Family history was significantly commoner for psychotic depression. There were no significant differences in life event scores. The HDRS factors – core depression, endogenous, insomnia and psychic anxiety – were similar to those of previous studies. Combining the HDRS and BPRS yielded factors that were more representative of the dimensions of depression. While family history distinguishes psychotic depression, life events are important with increasing age, but require interaction with predisposing factors. Although depression is heterogeneous, there are core clinical features which are stable across cultures and time. Family history is more associated with the severer forms of the disorder, and combining relevant questionnaires maybe more useful in research on symptom profiles.