bluuebunny/crossref_metadata_2025 huggingface dataset:
Homocysteine, Apolipoproteine E and Methylenetetrahydrofolate Reductase in Alzheimer’s Disease and Mild Cognitive Impairment
Authors: Religa D. , Styczynska M. , Peplonska B. , Gabryelewicz T. , Pfeffer A. , Chodakowska M. , Luczywek E. , Wasiak B. , Stepien K. , Golebiowski M. , Winblad B. , Barcikowska M.
Published: June 2003

Background: Alzheimer’s disease (AD) is the most common dementia disorder in elderly people. Currently, the only known genetic factor associated with the development of sporadic AD is the apolipoprotein E (ApoE) 4 allele. There is a need to identify other environmental and genetic risk factors that could modulate the risk of developing sporadic AD. Objective: To analyse the correlation between the ApoE and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and plasma homocysteine levels and vitamins (B12 and folic acid) concentrations in serum from patients with AD and mild cognitive impairment (MCI) as compared with control group. Methods: The study was carried out in 99 AD patients, 98 subjects with MCI and 100 healthy subjects. Diagnosis of probable AD was made according to the NINCDS-ADRDA and DSM-IV criteria. The following factors were analysed: age, gender, duration of disease, concentration of plasma total homocysteine, folic acid and vitamin B12 in the serum and the polymorphism of MTHRF and ApoE genes. The results obtained were analysed by multivariate analysis of regression. Results: We found that plasma total homocysteine is increased in AD patients (p < 0.0001) and depended on the MTHFR T/T genotype in the presence of low folate levels (p < 0.05). The increased frequency of ApoE4 allele in the AD population was independent of homocysteine, folic acid and vitamin B12 levels and MTHFR status. Conclusions: We conclude that the concentration of plasma total homocysteine is increased in AD patients. This may be associated with the T/T genotype in the MTHFR gene; however, the distribution of the MTHRF C677T polymorphism in the Polish population does not differ in AD and controls.
Progression of Dementia Associated with Lacunar Infarctions
Authors: Aharon-Peretz Judith , Daskovski Ella , Mashiach Tatiana , Kliot Dorita , Tomer Rachel
Published: June 2003

Background: Lacunar stroke (L) is the most common stroke subtype associated with vascular dementia (VaD-L). Objective: To evaluate the cognitive and behavioral course in patients with probable VaD-L. Methods: We longitudinally measured rates of change on MMSE, digit span, logical memory, Controlled Oral Word Association, CERAD battery and neuropsychiatric inventory (NPI) in 77 patients (age at entry 69 ± 8.1 years) with probable VaD-L for 25.75 ± 11 months. Results: The mean number of follow-up visits was 2.6 ± 0.67 (range 2–4). Time interval between any two consecutive visits was at least 5 months (range 5–41). MMSE deteriorated by 1.44± 1.8 points annually and NPI increased by 6.01 ± 13.7 points annually (p < 0.0001). The rates of cognitive and behavioral decline were predominantly influenced by the cognitive state at entry into the study and the occurrence of new vascular episodes during follow-up [(–0.95 ± 1.7) MMSE and (+2.02 ± 14.1) NPI points annually without vascular episodes vs. (–2.09 ± 1.6) and (+11.3 ± 11.4) points following vascular episodes (p < 0.0001)]. Impaired cognition was associated with impaired behavior (p < 0.001). VaD-L patients without additional vascular episodes at follow-up have a progressively deteriorating course as well (p < 0.0001). Conclusion: VaD-L is characterized by cognitive and behavioral decline. The rate of decline is determined mainly by the severity of the cognitive and behavioral impairment at baseline and by the occurrence of new vascular episodes.
Subjective Memory Complaints of Family Members of Patients with Alzheimer’s Disease and Depression
Authors: Heun Reinhard , Kockler Martin , Ptok Ursula
Published: June 2003

Background: First-degree relatives of patients with Alzheimer’s disease (AD) and major depression (MD) carry an increased genetic risk for the same disorders. Subjective memory complaints of the family members of patients might be an early sign or an indicator of an increased risk of either dementia or depression. Alternatively, they might be the consequence of the increased subjective awareness of relatives and spouses of patients of their own age-associated memory failures. To investigate the relevance of the above-mentioned hypotheses, the prevalence rates of subjective memory complaints of first-degree relatives and spouses of patients with AD, of patients with MD and of control subjects were compared. Methods: Personal interviews were conducted with 718 first-degree relatives and 196 spouses of 146 AD patients, 168 patients with MD and 136 control subjects from the general population. The prevalences of subjective memory complaints by relatives or spouses were compared using χ2 tests. To control for differences of gender and age at onset, Cox proportional hazards analyses were performed. Results: There were no differences in the prevalence of subjective memory complaints by first-degree relatives of subjects with AD, MD and controls after controlling for age differences. The same applies to the subjective memory complaints in their spouses. Conclusion: Subjective memory complaints were frequent in family members. However, they were neither associated with the genetic risk of AD or of MD nor could they be explained by an increased awareness by having a demented spouse or relative. Consequently, familial factors seem to have a limited influence on the presence of subjective memory complaints in the elderly.
Subjective Experience of Memory Deficits Related to Clinical and Neuroimaging Findings
Authors: Elfgren C. , Gustafson L. , Vestberg S. , Risberg J. , Rosén I. , Ryding E. , Passant U.
Published: June 2003

The aim of this study was to evaluate cognitive impairment, psychiatric symptoms and cerebral blood flow (CBF) patterns in middle-aged (35–64 years) and younger old patients (65–74 years) with subjective experience of memory deficits. The study group was heterogeneous with patients fulfilling criteria for dementia, as well as patients with mild cognitive impairment (MCI) and with non-verified cognitive impairment (non-MCI). Seventy per cent of the non-MCI patients reported long-lasting experiences of psychosocial stress tentatively causing the memory problems. The MCI patients were subdivided into two groups: MCI type 1 included patients with isolated memory impairment, while MCI type 2 included patients with memory impairment together with slight verbal and/or visuospatial impairments. CBF measurements comparing the two MCI groups with the non-MCI group were performed. The MCI type 2 showed reduced CBF in the left anterior medial temporal lobe as well as in parts of the posterior cingulate gyrus. The CBF pattern in MCI type 2 concurs with the pathophysiological process of Alzheimer’s disease. The results indicate that it is important to make a subdivision of MCI patients regarding the presence of isolated memory impairments or memory impairments together with other slight cognitive deficits.
Dementia Accompanying Motor Neuron Disease –7 Cases
Authors: Marquard Ralf , Bergida Robert , Müller Ruppert , Becker Ingrid , Wada Makoto , Kurz Alexander
Published: June 2003

Seven typical cases of dementia with motor neuron disease (D-MND) are reported. Among 1,000 dementia cases, D-MND was more frequent than Pick’s disease, Lewy body disease or Creutzfeldt-Jakob disease. D-MND accounted for 30.4% of all forms of frontal lobe dementia (FLD) including FLD and Pick’s disease. These data support that this combined syndrome may be more frequent than previously reported. As the subcortical neuropathology of D-MND is identical with MND, D-MND is rather the cortical manifestation of MND than a new disease entity.
Factor Structure of a Modified Version of the Wisconsin Card Sorting Test: An Analysis of Executive Deficit in Alzheimer’s Disease and Mild Cognitive Impairment
Authors: Nagahama Yasuhiro , Okina Tomoko , Suzuki Norio , Matsuzaki Shigeru , Yamauchi Hiroshi , Nabatame Hidehiko , Matsuda Minoru
Published: June 2003

In order to explore the factor structure of a modified version of the Wisconsin Card Sorting Test (mWCST) and to identify the dimensions of deficit in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI), conventional mWCST scores in 55 AD patients, 17 MCI patients, and 22 controls were subjected to factor analysis. Three factors, perseveration, inefficient sorting, and nonperseverative error, were obtained. Perseveration score was significantly poorer in both AD and MCI than in controls. By contrast, the MCI group showed significantly poorer scores on the nonperseverative error factor than did the AD patients, and the controls yielded intermediate values between the two patient groups. The perseveration factor was significantly correlated with the other estimates of executive function. This study suggested that the many mWCST scores could be reduced to three major factors, and that the perseveration score may effectively represent an aspect of executive dysfunction in AD and MCI patients.
Hyperintensities and Fronto-Subcortical Atrophy on MRI Are Substrates of Mild Cognitive Deficits after Stroke
Authors: Burton Emma , Ballard Clive , Stephens Sally , Kenny Rose Anne , Kalaria Raj , Barber Robert , O’Brien John
Published: June 2003

Aim: The current study determines the MRI correlations of the early neuropsychological post-stroke cognitive deficits. Method: Detailed neuropsychological assessments (attention and working memory) were undertaken in 50 stroke survivors >75 years of age [38 with ageing-associated cognitive decline (AACD)] and 15 age-matched controls. A 1.5-tesla General Electric MRI scanner was used. Standardized visual ratings were undertaken of white matter hyperintensities (WMH). Grey matter volumes were assessed using voxel-based morphometery. Results: Associations were identified between processing speed and executive function and the severity of WMH in key areas. In addition, atrophy in the fronto-subcortical circuits was associated with AACD. Conclusion: Attentional and executive impairments are underpinned by WMH in fronto-striato-thalamo-frontal circuits. Frontal atrophy is identified as a novel substrate of cognitive decline in stroke patients.
Effect of Dialysis on Plasma Total Antioxidant Capacity and Lipid Peroxidation Products in Patients with End-Stage Renal Failure
Authors: Samouilidou E. , Grapsa E.
Published: June 2003

Dialysis is associated with an impairment of antioxidant defense and an overproduction of oxidative stress markers. This study focuses on the comparison of plasma total antioxidant capacity (TAC) and lipid peroxidation products in patients on hemodialysis (HD) before and after treatment and in peritoneal dialysis (PD) patients. Plasma TAC, malonaldehyde (MDA), and 4-hydroxyalkenal concentrations were measured in 31 HD patients, in 24 PD patients, and in 17 normal controls (NC). It was found that before HD, TAC and MDA levels were higher than those in the NC (p < 0.001). After HD, these levels decreased significantly but were higher than in NC and lower than in PD patients (p < 0.001). The levels of 4-hydroxyalkenals were elevated in patients as compared with NC, but did not differ between HD and PD patients. The MDA concentrations correlated positively with the TAC in the patients. It is concluded that the oxidative status of patients on HD is similar to that of patients on PD and that the susceptibility to oxidative stress is strongly related to the levels of MDA produced in plasma.
Influence of Relative Hypoparathyroidism on the Responsiveness to Recombinant Human Erythropoietin in Hemodialysis Patients
Authors: Hsu Shih-Ping , Peng Yu-Sen , Pai Mei-Fen , Hung Kuan-Yu , Tsai Tun-Jun
Published: June 2003

Background/Aim: It has been shown in a few studies examining small patient groups that high levels of intact parathyroid hormone (iPTH) were associated with a less efficient response to recombinant human erythropoietin (rHuEPO). However, the responsiveness to rHuEPO in hemodialysis (HD) patients with relative hypoparathyroidism remains undetermined. This study examines the responsiveness to rHuEPO in HD patients with relative hypoparathyroidism. Methods: We retrospectively studied 19 nondiabetic patients (mean age 44.3 ± 8.2 years, age range 29.4–55.6 years) treated with HD for chronic glomerulonephritis. Of the 19 patients, 8 (group A) had iPTH levels <100 pg/ml for the preceding 6 months without administration of 1,25-(OH)2-vitamin D3. Eleven patients had iPTH levels >100 pg/ml (group B). Hematocrit (Hct) and rHuEPO doses were recorded for statistical analysis. Results: In patients of groups A and B, the rHuEPO dose (U/kg/week) was 55.21 ± 16.23 vs. 84.08 ± 24.56 (p = 0.01); Hct (%) 33.29 ± 1.72 vs. 31.43 ± 2.98 (p = 0.67), and rHuEPO resistance index (weekly rHuEPO dose/Hct) 81.38 ± 16.64 vs. 155.63 ± 42.22 (p < 0.001). Furthermore, weekly rHuEPO dose and rHuEPO resistance index correlated positively with serum iPTH levels (R = 0.765, p < 0.001; R = 0.764, p < 0.001), whereas the Hct correlated negatively with serum iPTH levels (R = –0.400, p = 0.045). The alkaline phosphatase level (IU/l) was lower (50.46 ± 12.87 vs. 69.61 ± 20.68, p = 0.17) in group A. Conclusion: Our observations suggest that the lower the iPTH levels of chronic HD patients, even with relative hypoparathyroidism, the better the responsiveness to rHuEPO.
Liver Support – A Task for Nephrologists? Extracorporeal Treatment of a Patient with Fulminant Wilson Crisis
Authors: Manz Tanja , Ochs Andreas , Bisse Emmanuel , Strey Christoph , Grotz Wolfgang
Published: June 2003

Background: Patients with Wilson’s disease may present with cirrhosis, acute hepatitis or fulminant hepatic failure. Without urgent orthotopic liver transplantation, a fulminant Wilson crisis has a mortality of 100%. We report on an 18-year-old female patient with fulminant hepatic failure due to Wilson crisis. Methods: The molecular adsorbent recirculating system (MARS) was used to eliminate albumin-bound toxins and to bridge waiting until an organ became available. Results: A total of 18 MARS sessions and 4 plasma exchange sessions were performed. Bilirubin levels and hepatic encephalopathy improved under MARS therapy. A total of 75 mg copper was removed until serum copper levels were within the normal range. Copper elimination was measured in 15 MARS treatments, which removed a total of 12.9 mg copper. Four plasma exchange sessions, with a total exchange of 11 liters of plasma, removed 12 mg copper. Urinary copper elimination with penicillamine was 50 mg. Conclusion: MARS was an effective method to stabilize a patient with Wilson crisis, contributed to copper elimination and gained time for liver transplantation. The risk of high-urgency transplantation could be avoided. Liver support was easy in the hands of nephrologists familiar with extracorporeal therapy.
Changes in Circulating Levels of Calcitonin Gene-Related Peptide and Nitric Oxide Metabolites in Septic Patients during Direct Hemoperfusion with Polymyxin B-Immobilized Fiber
Authors: Shimizu Tomoharu , Hanasawa Kazuyoshi , Tani Tohru , Endo Yoshihiro , Kurumi Yoshimasa , Ikeda Toshiaki , Fujita Naohiro , Morita Hiroyuki , Imaizumi Hitoshi , Sato Takashi , Katayama Hiroshi
Published: June 2003

Background/Aims: This study evaluated the mechanism of hemodynamic improvement in polymyxin B-immobilized fiber (PMX) treatment. Methods: Fifteen septic patients with endotoxemia and/or gram negative infection were treated with PMX. Plasma concentrations of calcitonin gene-related peptide (CGRP) and nitric oxide metabolites were measured. Results: CGRP and nitric oxide metabolites before treatment were significantly higher than in healthy controls. CGRP had a significantly inverse correlation with diastolic blood pressure and a positive correlation with the Septic Severity Score and the number of failed organs. Systolic and diastolic blood pressure and systemic vascular resistance index increased significantly both immediately after and 24 h after PMX treatment. CGRP decreased significantly 24 h after the treatment. In contrast, there were no significant changes in nitric oxide metabolites. Conclusion: PMX treatment improved hemodynamic parameters in septic patients, and CGRP increased with increasing severity of sepsis. We conclude that a decrease in CGRP levels may be related to hemodynamic improvement resulting from PMX treatments.
Role of Hypoxia in the Pathogenesis of Renal Disease
Authors: Eckardt Kai-Uwe , Rosenberger Christian , Jürgensen Jan Steffen , Wiesener Michael S.
Published: June 2003

Despite a high overall oxygen supply, the tissue oxygen tensions in the kidney are comparatively low and render the kidneys prone to hypoxic injury. However, the role of hypoxia in the pathogenesis of different types of renal disease remains incompletely understood. The importance of hypoxic cell injury is most obvious in renal vascular disease, in which occlusion of the renal artery or one of its branches can induce tissue necrosis. In acute renal failure, circumstantial evidence suggests that hypoxic injury to the renal medulla plays a significant role. In addition, chronically impaired oxygenation may also be an important factor in the progression of chronic renal disease. Destruction of the glomerular capillaries leads to hypoperfusion of the peritubular interstitium. Moreover, in focal disease, a compensatory increase in perfusion of other glomeruli may increase flow and pressure in peritubular capillaries derived from their vasa efferentia which could be a cause of microvascular injury. The interstitial capillary density is reduced in chronic renal disease, and results of animal experiments suggest that this is due to an imbalance in the expression of pro- and antiangiogenic factors. Besides its essential role in energy generation, oxygen is increasingly recognized as an important regulator of cellular functions. Hypoxia induces specific genes through increased expression of hypoxia-inducible transcription factors (HIF). Different HIF isoforms have recently been shown to be inducible in glomerular, tubular, and interstitial cells of the kidney. While the majority of HIF-dependent genes confer protection against hypoxia, hypoxia-inducible gene expression has been suggested to contribute also to increased interstitial matrix deposition.
Interleukin 18 and Interleukin 18 Binding Protein: Possible Role in Immunosuppression of Chronic Renal Failure
Authors: Dinarello Charles A. , Novick Daniela , Rubinstein Menachem , Lonnemann Gerhard
Published: June 2003

Although interleukin (IL)-18 is a member of the IL-1 family of ligands, IL-18 appears to have unique characteristics, particularly in the regulation of the T helper type 1 (Th1) response. Th1 responses are required for tumor surveillance, killing intracellular organisms, and to provide help for antibody production. In patients with chronic renal failure, the well-known immunosuppression contributes to a failure to respond to infectious challenges and vaccinations. The most salient biological property of IL-18, linking this cytokine to the Th1 response, is its ability to induce interferon gamma (IFN-γ). In fact, IL-18 was originally identified as an IFN-γ-inducing factor, and IFN-γ production is the hallmark of the Th1 response. Dysregulation of IFN-γ production resulting from reduced activity of IL-18 would explain one of the mechanisms of immunosuppression in patients with chronic renal failure. The activity of IL-18 can be regulated by the IL-18-binding protein (IL-18BP), a glycoprotein of 40,000 daltons, which is constitutively expressed and appears to be the natural inhibitor of IL-18 activity. Unlike soluble receptors for IL-18, IL-18BP does not have a transmembrane domain; IL-18BP is a secreted protein possessing a high-affinity binding and ability to neutralize IL-18. IL-18BP was discovered in human urine and is excreted in health following glomerular filtration. With decreasing renal function, the concentrations of IL-18BP in the circulation are elevated as compared with subjects with a normal renal function, and these elevated levels may result in a decreased IL-18 activity. Because of the importance of IL-18 and IFN-γ in the Th1 response, the biology of IL-18 and IL-18BP is reviewed here in the context of the immunosuppression of chronic renal failure.
Steroid Correlates of Territorial Behavior in Male Jacky Dragons, Amphibolurus muricatus
Authors: Watt Michael J. , Forster Gina L. , Joss Jean M.P.
Published: June 2003

Male jacky dragons, Amphibolurus muricatus, indicate territoriality to rivals during the mating season through the use of stereotyped motor displays. The relationship between corticosterone (B) and testosterone (T) and its effects on territorial display expression were investigated in captive lizards. Results demonstrated that territorial display production was most effectively predicted by elevated baseline T levels. This parallels the heightened T concentrations exhibited by males in the field during the spring mating period. The effect of social interaction on B and T levels was also examined by presenting territory-holding males with a size-matched male intruder. Resident males exhibited clear differences in the level of territorial response evoked by a male intruder, which were correlated with differences in physiological activity. Males that gave no territorial response had moderate B levels that did not change with social interaction, and significantly lower T levels than males that responded to the intruder with territorial displays. Among displaying males, those exhibiting low levels of territorial responses showed no change in B or T. In contrast, high-level territorial responders exhibited acute B increases when faced with an intruder, which might assist in supporting sustained metabolic activity and could possibly reflect differences in the perception of social stress. These same males also exhibited a reduction in T levels at such times, probably due to the acute rise in B. Combined, these results suggest that high circulating T is acting in a preparatory manner to increase the likelihood of producing a territorial response upon engaging in a social encounter. However, once this response has been initiated T may not need to remain elevated to allow continued expression of territorial behavior.
Effects of Running Water on Lateral Line Responses to Moving Objects
Authors: Engelmann Jacob , Kröther Sophia , Bleckmann Horst , Mogdans Joachim
Published: June 2003

We investigated in goldfish, Carassius auratus, and trout, Oncorhynchus mykiss, how running water affects the responses of afferent fibers in the posterior lateral line nerve and of lateral line units in the brainstem medial octavolateralis nucleus to an object that is moved from anterior to posterior or opposite along the side of the fish. In still water, nerve fibers in both species responded to the moving object with alternating periods of increased and decreased firing rate. Most fibers in goldfish but none in trout discharged bursts of spikes in response to the object’s wake. Responses of brainstem units were more variable and less distinct than nerve fiber responses. Bursting activity in response to the object’s wake was found in only one brainstem unit. In running water, responses of goldfish nerve fibers were weaker than in still water. This effect was independent of object motion direction. Responses of trout fibers were weaker when the object was moved with the flow but were slightly stronger when the object was moved against the flow. In general, running water affected the responses of goldfish nerve fibers more strongly than the responses of trout fibers. Compared to still water, brainstem units in both species responded more weakly when the object was moved with the flow. When the object was moved against the flow, brainstem responses were on average comparable to those in still water. Measurements of changes in pressure and water velocity caused by the moving object indicate that the observed effects can largely be explained by peripheral hydrodynamic effects. However, physiological differences between goldfish and trout units indicate that the lateral line systems in these two species are adapted to different hydrodynamic conditions.
Persistence of the Nitric Oxide Pathway in the Aorta of Hypercholesterolemic Apolipoprotein-E-Deficient Mice
Authors: Villeneuve Nicole , Fortuno Ana , Sauvage Marie , Fournier Nancy , Breugnot Christine , Jacquemin Christine , Petit Christine , Gosgnach Willy , Carpentier Nathalie , Vanhoutte Paul , Vilaine Jean-Paul
Published: June 2003

The markers of the bioavailability of NO (endothelium-dependent relaxation to acetylcholine and cyclic GMP content) in the thoracic aorta of apolipoprotein-E-deficient (ApoE KO) mice, 20 weeks old with enriched cholesterol diet or 35 weeks old on regular chow, are not decreased, in contrast with other models of atherosclerosis. However, severe hypercholesterolemia, the presence of atherosclerotic lesions and increased NADPH oxidase activity have been reported as early as at 20 weeks of age. The present experiments were designed to test if an increased capacity of NO production in these mice explains this paradox. The expressions of the 3 isoforms of NO synthase (NOS) were compared in ApoE KO and C57Bl/6J mice using Western blot and localized by immunohistochemistry. No adaptive increase in the expression of NOS was detected in ApoE KO mice. NO bioavailability could also be preserved by upregulation of enzymes involved in redox status such as CuZn or Mn superoxide dismutase and catalase. However, these enzymes were less expressed in ApoE KO mice than in control mice. These results highlight that ApoE KO mice represent an atypical model of atherosclerosis.
Different Growth Properties of Neointimal and Medial Smooth Muscle Cells in Response to Growth Factors
Authors: Myit Samir , Delafontaine Patrick , Bochaton-Piallat Marie-Luce , Giraud Stephane , Gabbiani Giulio , Brink Marijke
Published: June 2003

Different smooth muscle cell phenotypes coexist in arteries. The majority of cells cultured from a normal rat aortic media have a spindle-shaped phenotype while cells isolated from an intimal thickening 15 days after endothelial injury show a distinct epithelioid phenotype. These two phenotypes express their own specific set of genes and differ in their proliferation and migration characteristics. We studied growth factor-induced DNA synthesis in both phenotypes and investigated the potential mechanisms behind the differences in growth characteristics. Insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF-BB), and basic fibroblast growth factor (FGF) increased thymidine incorporation in both phenotypes, but the increase was markedly stronger in neointimal cells than in medial cells. Northern blot analysis 30 min after growth factor stimulation showed that c-fos and c-jun mRNAs were induced more strongly in neointimal than in medial cells. IGF-I receptor and PDGF-Rβ levels were higher in neointimal cells than in medial cells, but the FGF receptor level was not different between the cell types. In summary, our results indicate that neointimal cells are more sensitive to growth factors than medial cells, likely due to a higher expression of IGF-I receptor and PDGF-Rβ. Our results provide insight into the mechanism by which epithelioid cells play a primary role in vascular neointima formation.
The Effect of the Nitric Oxide Synthase Inhibitor N-Nitro-L-Arginine-Methyl Ester on Neuropeptide-Induced Vasodilation and Protein Extravasation in Human Skin
Authors: Klede Monika , Clough Geraldine , Lischetzki Grischa , Schmelz Martin
Published: June 2003

Endogenous neuropeptides released from nociceptors can induce vasodilation and enhanced protein extravasation (neurogenic inflammation). The role of nitric oxide (NO) in the induction of neurogenic inflammation is controversial. In this study, dermal microdialysis was used in awake humans (n = 39) to deliver substance P (SP; 10–7 and 10–6M) or calcitonin gene-related peptide (CGRP; 5 × 10–7M and 2 × 10–6M). Neuropeptide-induced local and axon reflex erythema was assessed by laser Doppler imaging. Total protein concentration in the dialysate was measured to quantify local protein extravasation. The responses were assessed in the absence and the presence of the nitric oxide synthase inhibitor, N-nitro-L-arginine-methyl ester (L-NAME) added to the perfusate at concentrations of 5, 10 or 20 mM. L-NAME (5 mM) applied via the dialysis catheters reduced local blood flow by approximately 30%. In addition, L-NAME inhibited SP-induced vasodilation by about 40% for 10–7M SP and 30% for 10–6M SP (n = 11, p < 0.01). In contrast, CGRP-induced vasodilation was only marginally inhibited by L-NAME. SP, but not CGRP, provoked a dose-dependent increase in protein extravasation. L-NAME (5 mM) inhibited this increase by up to 40% for both SP concentrations used (n = 11, p < 0.01). Higher concentrations of L-NAME did not further reduce SP- or CGRP-induced vasodilation or SP-induced protein extravasation. Exogenously applied SP induces vasodilation and protein extravasation, which is partly NO mediated, whereas CGRP-induced vasodilation appears to be NO independent.
Co-Infection with Chlamydia pneumoniae and Helicobacter pylori Results in Vascular Endothelial Dysfunction and Enhanced VCAM-1 Expression in ApoE-Knockout Mice
Authors: Liuba Petru , Pesonen Erkki , Paakkari Ilari , Batra Satish , Andersen Leif , Forslid Anders , Ylä-Herttuala Seppo , Persson Kenneth , Wadström Torkel , Wang Xin , Laurini Ricardo
Published: June 2003

Background: Upregulation of proinflammatory endothelial cell adhesion molecules and decreased bioactivity of endothelial nitric oxide (NO) are important in the pathogenesis of atherosclerosis. We investigated the effects of co-infection with Chlamydia pneumoniae and Helicobacter pylori on these two events in apoE-KO mice. Methods: Thirty-two apoE-KO mice, 8 weeks old, were equally divided into 4 groups. The first 2 groups were infected with either C. pneumoniae or H. pylori, while the 3rd group was infected with both C. pneumoniae and H. pylori. Mice from the 4th group and 4 wild-type mice served as controls. Thoracic and abdominal aortas were harvested after 10 weeks, and staining for vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 was analyzed by immunocytochemistry. The endothelial vasomotor responses of thoracic aortas to methacholine were studied in organ chambers in the absence and presence of L-NAME. The plasma levels of nitrate/nitrite were measured. Results: Staining for VCAM-1 was more intense at the branching sites of aortas from mice with co-infection than in mono-infected or noninfected apoE-KO mice. The relaxation responses to methacholine and the plasma levels of nitrate/nitrite were significantly less in the co-infected group than in the other groups (p < 0.05). Conclusion: Co-infection of apoE-KO mice with C. pneumoniae and H. pylori seems to be associated with impaired bioactivity of endothelial NO and increased expression of VCAM-1 at branching sites. The findings may suggest an additive interaction of these pathogens in atherogenesis.
Heterogeneity in the Acute Control of Vascular Protein Synthesis in vivo
Authors: Beaucage Pierre , Yamaguchi Nobuharu , Larivière Richard , Moreau Pierre
Published: June 2003

In response to both hemodynamic and neurohumoral changes, the cardiovascular system remodels and this process could contribute to end organ damage. The aim of this study was to determine the early in vivo interactions between 3 systems known to contribute to vascular hypertrophic remodeling, in conduit and resistance arteries. Exogenous angiotensin II, norepinephrine and endothelin 1 administration elevated protein synthesis in the aorta and in small mesenteric arteries. In small arteries, the effect of angiotensin II was blocked by angiotensin II type 1, α-adrenergic and endothelin receptor antagonists, while only the α-adrenergic and endothelin receptor antagonists inhibited the effect of norepinephrine. Moreover, only the endothelin receptor antagonist significantly blunted the effect of exogenous endothelin on protein synthesis. In the aorta, the stimulation of angiotensin II on protein synthesis was also inhibited by the 3 antagonists. However, only the α-adrenoceptor antagonist blunted the response to norepinephrine, and the 3 antagonists prevented the endothelin-induced elevation of protein synthesis. The blood pressure effects of the drugs did not correlate with their capacity to stimulate or inhibit vascular protein synthesis. In conclusion, interactions in the control of protein synthesis are heterogeneous along the vascular tree. In small arteries, the interaction is linear with endothelin as the downstream effector. In the aorta, the local sympathetic nervous system appears to control protein synthesis. The heterogeneity in downstream effectors should be considered in studies investigating signaling events related to protein synthesis, which is used as an early marker of hypertrophy.
Evidence for a Differential Cellular Distribution of Inward Rectifier K Channels in the Rat Isolated Mesenteric Artery
Authors: Crane G.J. , Walker S.D. , Dora K.A. , Garland C.J.
Published: June 2003

The distribution of functionally active, inwardly rectifying K (KIR) channels was investigated in the rat small mesenteric artery using both freshly isolated smooth muscle and endothelial cells and small arterial segments. In Ca2+-free solution, endothelial cells displayed a KIR current with a maximum amplitude of 190 ± 16 pA at –150 mV and sensitivity to block with 30 µM Ba2+ (n = 7). In smooth muscle cells, outward K current was activated at around –47 ± 3 mV, but there was no evidence of KIR current (n = 6). Furthermore, raising extracellular [K+] to either 60 or 140 mM, or applying the α1-adrenoceptor agonist phenylephrine (PE; 30 µM), failed to reveal an inwardly rectifying current in the smooth muscle cells, although PE did stimulate an iberiotoxin-sensitive outward K current (n = 4). Exogenous K+ (10.8–16.8 mM) both relaxed and repolarized endothelium-denuded segments of the mesenteric artery contracted with PE. These effects were depressed by 100 µM ouabain but unaffected by either 30 µM BaCl2 or 3 µM glibenclamide. These data suggest that functional, inwardly rectifying Ba2+-sensitive channels are restricted to the endothelial cell layer in the rat small mesenteric artery.
Use of Antidepressant Medications and the Possible Association with Breast Cancer Risk
Authors: Bahl Saira , Cotterchio Michelle , Kreiger Nancy
Published: June 2003

Background: Antidepressant medication use has dramatically increased over the past decade, particularly for the newer classes such as selective serotonin reuptake inhibitors. While there is no question about the usefulness of these medications, it is important to review animal and epidemiologic studies that have evaluated the association between antidepressant medication use and the risk of breast cancer. Methods: This paper reviews the scientific literature pertaining to the prevalence of and indications for antidepressant medication use, and the possible association between antidepressant medication use and breast cancer risk. Results: Antidepressant medications are most commonly indicated for depressive disorders, and are also used for other conditions (e.g., anxiety disorders, personality disorders, and pain). In addition, antidepressants may be an effective alternative to estrogen therapy for the alleviation of hot flashes among peri-/postmenopausal women. Several epidemiologic studies have reported that certain antidepressants may be associated with a slightly increased breast cancer risk; however, the literature remains inconsistent. Conclusions: The possibility of an association between certain antidepressant medications and breast cancer risk has not been excluded, although further studies are needed before the body of scientific evidence can be conclusive. Evidence to date does not support a change in the current use of antidepressant medications.
Anxiety Sensitivity Profile: Dimensional Structure and Relationship with Temperament and Character
Authors: van der Does Willem , Duijsens Inge , Eurelings-Bontekoe Elisabeth , Verschuur Margot , Spinhoven Philip
Published: June 2003

Background: Anxiety sensitivity (AS), the belief that bodily sensations have harmful consequences, is a reliable predictor of panic attacks in both clinical and nonclinical populations. Recently, a new measure of AS has been proposed. The AS profile (ASP) was designed to be a more comprehensive measure of AS, and to be more suitable for the measurement of different AS dimensions. Preliminary evidence (college student sample) suggests that the ASP has 4 dimensions. In the present study, the dimensional structure of the ASP was further investigated, as well as its relationship with temperament and character traits. Methods: Exploratory and confirmatory factor analysis of ASP scores in two large samples of psychiatric outpatients and nonclinical controls (combined n = 742). Correlations and partial correlations of ASP with temperament and character. Results: Exploratory factor analysis yielded a single AS factor. However, confirmatory factor analysis showed that the 6-dimensional structure, as Taylor and Cox had originally intended it, might be a defendable solution. However, the number of items is much too high, with many subscales consisting of semantic clusters. ASP scores were found to be weakly related to the temperament dimension harm avoidance, corroborating earlier findings that were not statistically significant because of small sample sizes. Conclusions: The ASP may be shortened from 60 to 24 items without loss of reliability or content. Future studies using challenge paradigms and studies with general hospital patients may further investigate the usefulness of a shortened version of the ASP.
Routine Monitoring of Outcome over 11 Years in a Residential Behavioural Psychotherapy Unit
Authors: McKenzie Nigel , Marks Isaac
Published: June 2003

Background: Though research trials have to rate clinical outcome, few units monitor outcome of their routine care over many years. We report such monitoring to evaluate therapy over time and under changing operating and economic conditions. Method: Clinical outcome data were collected routinely over 11 years in a behavioural psychotherapy unit whose residential patients mostly had severe, chronic obsessive-compulsive disorder (OCD) treated by self-exposure therapy. Data were from 218 referrals during 4 of the 11 available years. Results: In each of the 4 time periods, the patients improved consistently and highly significantly by 30–50% on symptoms and disability, which resembled outcome in a multi-centre controlled trial. There were almost no significant differences in pre-treatment ratings between patients who attended follow-up, patients who completed residential treatment but not follow-up and those who did not complete residential treatment. When the unit became a hostel and the UK government introduced an internal market, more chronic patients were admitted who often lived far away. Conclusions: The fact that successive OCD cohorts had improved comparably by discharge suggests there was no ‘burn-out’ in staff standards of care over 11 years, and no loss of gains when the unit became a more cost-effective hostel.
Die «Gynäkologisch-geburtshilfliche Rundschau» steht vor einer neuen Herausforderung!
Authors: Haller U. , Hepp H. , Winter R.
Published: June 2003

Die Österreichische Gesellschaft für Gynäkologie und Geburtshilfe (OeGGG) kündigte die Organschaft und damit das Pflichtabonnement bei der «Gynäkologisch-geburtshilflichen Rundschau» zugunsten einer berufspolitischen Zeitschrift. Damit wird einer langen und länderübergreifenden Tradition ein Schlusspunkt gesetzt. Dies bedeutet eine neue Herausforderung für die «Gynäkologisch-geburtshilfliche Rundschau».
Die Bedeutung einer gynäkologischen Teenagersprechstunde am Beispiel von «First Love»
Authors: Neudecker C. , Olechowski M. , Grünberger W.
Published: June 2003

Weltweit wird die Diskrepanz zwischen zahlreichen traditionellen Beratungsangeboten und ungenügender Aufklärung von Teenagern beklagt. An dem Beispiel von «First Love» konnte in den letzten 10 Jahren bewiesen werden, dass es sich lohnt, Jugendlichen eine kostenlose, anonyme und unkonventionelle Einrichtung anzubieten. So können unter Einbeziehung der individuellen (familiären und altersspezifischen) Lebenswelten junger Mädchen und ihrer Partner gemeinsam Konzepte entwickelt werden, um Sexualität geschützt, verantwortungsbewusst und lustvoll leben zu können. Beachtenswert ist auch der gesundheitspolitische Effekt im Sinne einer präventivmedizinischen Einrichtung. Wenn die erste gynäkologische Untersuchung als schmerzlos und selbstbestimmt erfahren wird, ist die Basis für lebenslange angstfreie Vorsorgeuntersuchungen geschaffen. Vor diesem Hintergrund wird die Bedeutung jugendgerechter Sexualberatung und Aufklärung auch für niedergelassene Ärzte und Ärztinnen deutlich.
Sexuelle Gewalt in der Adoleszenz: Befunderhebung, Sinn und Notwendigkeit der körperlichen Untersuchung
Authors: Navratil Francesca
Published: June 2003

Sexuelle Gewalt ist ein häufiges Problem, das Kinder und Jugendliche beider Geschlechter, in jedem Alter und jeder sozialen Schicht betreffen kann. In verschiedenen Studien konnte gezeigt werden, dass 10–22% der Jugendlichen Opfer sexueller Gewalt sind. Die Opfer zeigen, unter anderem, Verhaltensweisen, die im Endergebnis ein Risiko darstellen, wie die frühe Aufnahme von sexuellen Beziehungen, ungeschützten Geschlechtsverkehr mit multiplen Partnern und die damit verbundenen möglichen schwerwiegenden Konsequenzen einer unerwünschten Schwangerschaft oder sexuell übertragener Erkrankungen. Es ist wichtig, dass Fachleute, die Jugendliche betreuen, beraten, untersuchen und behandeln, dieses Problem kennen, erkennen und es auch ansprechen, um bei einer Gewaltsituation deren verheerende psychosoziale und somatische Folgen frühzeitig zu erkennen und entsprechend einzugreifen. Eine körperliche Untersuchung ist immer indiziert. Sie besteht in einer Allgemeinuntersuchung, einer genauen Genitoanalinspektion und je nach Anamnese einer instrumentellen gynäkologischen Untersuchung. Es ist wichtig zu wissen, dass ein normaler Genitoanalbefund eine sexuelle Missbrauchssituation nicht ausschliesst und dass eine multidisziplinäre medizinisch-psychosoziale Intervention immer angestrebt werden sollte.
Hormonelle Störungen im Zusammenhang mit Blutungsanomalien und späterer Fertilität
Authors: Tscherne G.
Published: June 2003

Im Laufe der Entwicklung der hypothalamisch-hypophysär-ovariellen Achse und der hormonellen Regulationsmechanismen bis zur Etablierung eines normalen ovulatorischen Zyklus sind in der Pubertät und Adoleszenz Blutungsanomalien häufig. Hormonelle Störungen sollten früh erkannt und richtig eingestuft werden, um mögliche nachteilige Folgen hintanzuhalten. Das gilt insbesondere für die spätere Fertilität. Ausgeprägte und persistierende Anomalien erfordern eine exakte Abklärung und zielgerichtete Behandlung. Bei Oligo-Amenorrhö, deren hormonelle Ursachen durch Hormonanalyse erfassbar sind, ist die richtige Zuordnung und Einschätzung wesentlich. Die Prognose betreffend spätere Fertilität hängt von Art und Schweregrad ab. Bei hypothalamischen Formen ist die Prognose gut, weil überwiegend eine Normalisierung des Zyklus nach Wegfall der verursachenden Noxen eintritt. Hypophysäre Läsionen wie auch eine Hyperprolaktinämie können erfolgreich behandelt werden. Im Fall der häufigen hyperandrogenämischen Anomalien, insbesondere des polyzystischen Ovar-Syndroms, ist die spätere Fertilität beeinträchtigt. Eine Verbesserung ist durch präventive und therapeutische Massnahmen in der Adoleszenz anzustreben. Bei Patientinnen mit einer primären Ovarialinsuffizienz ist speziell bei persistierender hypergonadotroper Amenorrhö die Prognose schlecht bis absolut negativ.
Mütterliche Mortalität in der Schweiz 1985–1994
Authors: Meili Gesine , Huch Renate , Huch Albert , Zimmermann Roland
Published: June 2003

In den letzten 100 Jahren ist die mütterliche Mortalität in den westlichen Ländern massiv gesunken. Aktuelle und detaillierte Zahlen über die Ursachen in der Schweiz existieren jedoch nicht. Ausgehend von den damals mit ICD-8 kodierten öffentlich erfassten Müttersterbefällen der Jahre 1985–1994 haben wir mit einer direkten Einsicht in die anonymisierten Krankenakten die Fälle präziser klassieren können. Wir teilten sie in direkte und indirekte Müttersterbefälle ein. Von primär 76 registrierten Fällen blieben 45 direkte Todesfälle auf 812825 Geburten, was einer direkten Müttersterblichkeit von 5,4/100000 Lebendgeburten entspricht. Die übrigen Fälle mussten umklassiert werden (indirekte, nicht schwangerschaftsbedingte und späte Müttersterbefälle). Am häufigsten starben Mütter an einer Thromboembolie (15%). Die Sektioletalität betrug 0,09‰. Die grosse Zahl von umklassierten Fällen zeigt, dass eine Unterweisung im Ausfüllen der Todeszertifikate nötig wäre. Beim Bestreben, die Müttersterblichkeit weiter zu senken, muss das Augenmerk auf eine konsequente Thromboembolieprophylaxe und eine frühe Entbindung bei HELLP-Syndrom gerichtet werden.
Following the Expression of a Kidney-Specific Gene from Early Development to Adulthood
Authors: Igarashi Peter
Published: June 2003

Ksp-cadherin (Cadherin 16) is a unique, tissue-specific member of the cadherin family of cell adhesion proteins that is expressed exclusively in tubular epithelial cells in the adult kidney and developing genitourinary (GU) tract. Since its original identification in 1995, Ksp-cadherin has proven to be a useful experimental model for studies of kidney-specific and developmental gene regulation. These investigations have led to the creation of new strains of transgenic mice that will be useful for studies of renal cell lineage and tissue-specific gene targeting. Recent studies have also identified Ksp-cadherin as the first kidney-specific promoter that it is regulated by HNF-1β (hepatocyte nuclear factor-1β), a transcription factor that has been implicated in human renal cystic disease.
Intravital Imaging of the Kidney Using Multiparameter Multiphoton Microscopy
Authors: Dunn Kenneth W. , Sandoval Ruben M. , Molitoris Bruce A.
Published: June 2003

Intravital optical microscopy provides a powerful means of studying the cell biology in the most physiologically relevant setting. The ability of multiphoton microscopy to collect optical sections deep into biological tissues has opened up the field of intravital microscopy to high-resolution studies of multiple organs. Presented here are examples of how two-photon microscopy can be applied to intravital studies of kidney physiology and the study of disease processes. These include studies of cell vitality and apoptosis, fluid transport, receptor-mediated endocytosis, blood flow, and leukocyte trafficking. Efficient two-photon excitation of multiple fluorophores permits comparison of multiple probes and simultaneous characterization of multiple parameters. Two-photon microscopy can now provide a level of investigation previously unattainable in intravital microscopy, enabling kinetic analyses and physiological studies of the organs of living animals with subcellular resolution. Therefore, application of this technology will provide direct visualization of organ-specific and cell-specific responses to an array of stimuli and therapeutic approaches, enhancing our understanding and treatment of disease processes.