bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired Water Excretion in a Hyponatremic Patient following Thyroidectomy: Causal Role of Glucocorticoid Deficiency
Authors: Yonemura Katsuhiko , Furuya Ryuichi , Oki Yutaka , Matsushima Hideki , Ohishi Kazuhisa , Hishida Akira
Published: April 2003

We evaluated the causal role of glucocorticoid deficiency in the hyponatremia that developed in a 57-year-old Japanese man with hypothyroidism following the performance of a total thyroidectomy for laryngeal cancer. The plasma concentration of vasopressin (1.78 pg/ml) was not suppressed in the presence of hyponatremia (125 mEq/l). The urinary excretion of sodium was increased, and the plasma renin activity and plasma aldosterone concentration were suppressed. The infusion of hypertonic saline increased the plasma osmolality, but not the plasma concentration of vasopressin. An oral water load (20 ml/kg of body weight) did not suppress the plasma vasopressin level or induce diuresis. Pretreatment with hydrocortisone normalized the response of plasma vasopressin to the water load was well as the diuretic response during the hypothyroid state. The urinary exretion of 17-hydroxycorticosteroids was below normal in the hypothyroid state in the face of normal serum cortisol concentration. The correction of the hypothyroidism returned these abnormalities to normal. A disturbed metabolism of glucocorticoid may have been responsible for the hyponatremia and disturbance in plasma vasopressin regulation observed in this hypothyroid patient.
Hypomagnesemia and Smooth Muscle Contractility:Diffuse Esophageal Spasm in anOld Female Patient
Authors: Iannello Silvia , Spina Maurizio , Leotta Paolo , Prestipino Marcella , Spina Sebastiano , Ricciardi Nunziato , Belfiore Francesco
Published: April 2003

The aim of this paper is to describe and discuss, on the basis of the available literature, the case of an old female patient, admitted to our university hospital because of a severe dysphagia for solid foods, in whom laboratory data showed a marked hypomagnesemia. She reported a long history (20 years) of allergic bronchial asthma treated with theophylline. Esophagography evidenced a disorder of esophagus motility with diffuse multiple spasm, reminiscent of the ‘corkscrew esophagus’. A link with the severe hypomagnesemia (Mg 1.1 mEq/l, normal range 1.6–2.1) was suspected, and a therapy with oral pidolate of Mg (1.5 g/twice a day) was started and continued for 4 months. This was associated with a slow progressive normalization of the Mg plasma level and reverted radiographic esophageal findings with disappearance of dysphagia. Mg is an important element for health and disease, and today Mg deficiency in man has become an accepted medical problem which might complicate many diseases. Neuromuscular disorders, as laryngeal spasm, are recognized complications of hypomagnesemia, but until now only 1 case of motor esophageal disorder associated with a low Mg plasma level was briefly reported in the literature, even if dysphagia is generally included in the symptomatological pattern of hypomagnesemia. Our observation of a severe form of esophageal spasm, associated with hypomagnesemia, in an aged female patient underlines the pathophysiological meaning of the plasma Mg level and suggests the need for routine Mg determination in the clinical setting.
Renin-Angiotensin-Aldosterone-Kinin System Influences on Diabetic Vascular Disease and Cardiomyopathy
Authors: Flack John , Hamaty Marwan , Staffileno Beth
Published: April 2003

Diabetes mellitus is associated with an inordinately high risk of virtually all manifestations of cardiovascular-renal disease including atherosclerotic coronary and peripheral vascular disease, congestive heart failure, stroke, nephropathy, and cardiomyopathy unassociated with coronary heart disease. Abnormalities in the renin-angiotensin-aldosterone-kinin (RAAK) cascade have been implicated in the pathogenesis and clinical expression of these cardiovascular-renal sequelae. Thus, pharmacological modulation of the RAAK system is an attractive therapeutic target in diabetes mellitus. Indeed, emerging data from human clinical studies appear to confirm this thesis.
Leptin and Its Clinical Implications in Chronic Renal Failure
Authors: Stenvinkel P.
Published: April 2003

Leptin, the recently identified ob gene product, regulates food intake and energy expenditure in animal models. Leptin reaches the brain by a saturable transport mechanism and, via direct effects on the hypothalamus, decreases appetite and increases metabolism. Several recent studies have demonstrated markedly elevated serum leptin levels in patients with chronic renal failure (CRF) and it has been speculated that hyperleptinemia may contribute to uremic anorexia and malnutrition. Several factors may influence serum leptin levels in uremia and apart from decreased glomerular filtration rate also body fat mass and plasma insulin levels are important factors that determine serum leptin levels. The possible influence of chronic inflammation on serum leptin levels in CRF need further studies. Patients treated by peritoneal dialysis seem to have higher leptin levels compared to patients treated by hemodialysis. This could be the effect of a marked increase in body fat mass as a consequence of the continuous carbohydrate load. Leptin receptors have by now been identified in several peripheal organs which suggests that leptin besides having central effects also has a pleiotropic action. Indeed, recent findings indicate that besides regulating appetite leptin may play a role in sympathico-activation, insulin metabolism, renal sodium handing and hematopoiesis.
Low Protein Diets Are Not Needed in Chronic Renal Failure
Authors: Mehrotra Rajnish , Nolph Karl
Published: April 2003

Low protein diets have been used for a long time in the conservative management of chronic renal failure as they have a beneficial effect in preventing the appearance of symptoms. However, with the exception of the beneficial effect on hyperphosphatemia of the very low protein diets supplemented with ketoacids, they have no proven effects on the other aspects of the uremic syndrome. Moreover, the weight of the evidence suggests that the effect of these diets on preservation of GFR, if any, in patients with nondiabetic renal disease is small and of little clinical relevance. There is very little evidence in the literature of its role in patients with diabetes. The nutritional safety of these diets is still suspect. Patients with chronic renal failure have low energy intakes, which is further reduced when these diets are prescribed. Metabolic studies predict that these patients would be in negative nitrogen balance and in fact, even nutritionally sound, nondiabetic patients enrolled in the Modification of Diet in Renal Disease Study developed subclinical signs of malnutrition. It is possible that the nutritional decline may have been more pronounced on longer duration of follow-up. Finally, these diets are difficult to follow, leading to issues of compliance and exert a great toll on the time of the dietitians. Hence, we conclude that low protein diets are not necessary in chronic renal failure.
Fluoride Is Unable to Reduce Dental Erosion from Soft Drinks
Authors: Larsen M.J. , Richards A.
Published: April 2003

The main aim of the present study was to compare the erosive capabilities of some fruit-flavoured drinks, fresh or saturated with CaF2, with their content of acids and with previous results from some carbonated soft drinks. The other aim was to measure and compare the rates of dissolution of CaF2 in some carbonated and non-carbonated drinks and water. Seven commercially available fruit-flavoured drinks were diluted for drinking. Two human molars, each with two approximately 4 × 4 mm windows, were exposed continuously to 500 ml of each drink with or without prior equilibration with CaF2 under gentle agitation for 48 h. The depths of the erosions were then measured on microradiographs made from sections. Dissolution rate of CaF2 was measured by suspending 0.5 g of the salt in 0.5 litre of the drinks for 2, 10 and 60 min followed by solution analysis. The pH of the drinks was 2.83–3.51. The amount of NaOH required to bring pH to 5.5 ranged from 12–42 mmol/l, which is more than the amount necessary for most carbonated soft drinks. Equilibration with CaF2 gave total fluoride concentrations of 3–8 ppm. The depths of the lesions induced by the drinks without added fluoride were 450–625 µm whilst those developed by the drinks equilibrated with CaF2 were 350–625 µm. The dissolution of CaF2 was faster in the carbonated drinks and in distilled water than in the non-carbonated drinks. In conclusion, non-carbonated fruit-flavoured drinks contain considerable amounts of acids which, in vitro, induce erosions in teeth similar to those induced by carbonated soft drinks. Saturation with CaF2 reduced the in vitro development of erosions by 28% induced by drinks with pH above 3; in drinks with pH below 3, erosions were not affected by pH, despite total fluoride concentrations of up to 20 ppm.
Intracardiac Thrombus in a Patient with Autoimmune Hemolytic Anemia Leading to a Diagnosis of Antiphospholipid Syndrome
Authors: Latagliata Roberto , Celesti Francesca , Bongarzoni Velia , Di Nucci Giandomenico , Torromeo Concetta , Morano Salvatore Giacomo , Cimino Giuseppe , Alimena Giuliana
Published: April 2003

We report a case of antiphospholipid syndrome (APS) which presented with clinical and laboratory signs of an autoimmune hemolytic anemia (AHA), in the absence of manifestations typically related to APS. The diagnosis of APS was made only after the occurrence of a sudden severe heart failure due to an intraventricular thrombus requiring a surgical approach. An accurate thrombophilic screening is warranted also in patients with apparently idiopathic AHA.
Mycoplasma-Associated Carditis
Authors: Paz Alona , Potasman Israel
Published: April 2003

We present 2 cases and examine the developments that occurred in diagnosis, treatment, and outcome of 19 additional patients with mycoplasmal peri- and myocarditis. The mean age of this group was 33 years. The final diagnoses were pericarditis (n = 15), myocarditis (n = 5), and myopericarditis (n = 1); pulmonary involvement was noted in 13 patients. Serology established the diagnosis in 12 cases, and isolation in 9 others. In contrast to previous reviews, an echocardiogram was carried out in all patients, thus enabling pericardiocentesis in 13 patients. Antibiotics were given to 19 patients, including 4 who received a newer macrolide. Three patients were left with long-term sequelae, and 1 patient died. The outcome of Mycoplasma carditis has improved over the years, although a minority of patients may suffer long-term sequelae.
Metoprolol Treatment to Prevent Restenosis following Percutaneous Transluminal Coronary Angioplasty
Authors: Franzen Damian , Seifert Nathalie , Metha Angela , Höpp Hans W.
Published: April 2003

This study tested the hypothesis that metoprolol reduces the restenosis rate after percutaneous transluminal coronary angioplasty (PTCA) in native coronary arteries as compared to placebo. Apart from prognostic clinical effects in the treatment of patients with coronary heart disease, several in vivo and ex vivo studies have demonstrated antiproliferative and antiatherogenic effects of beta-blockers. In the present study, 192 male patients were randomized in a double-blind fashion to metoprolol sustained-release treatment or placebo starting at least 1 day before angioplasty. Lesion diameters and restenosis rates were evaluated using automatic edge detection systems. The study endpoint was the angiographic restenosis rate 4 months after PTCA. Ninety-seven randomized patients had a control angiography a mean of 4.5 months after PTCA. Dropouts were evenly distributed between the metoprolol and placebo groups. Lumen loss in the target lesion was 0.36 mm in the metoprolol group and 0.32 mm in the placebo group. Restenosis rates averaged 57.5% in the metoprolol group and 44.2% in the placebo group using conventional restenosis criteria. Taking metoprolol serum levels above 50 mmol/l as an indication of definite compliance with the metoprolol treatment, the restenosis rate was 58.3%. In conclusion, 95 mg of sustained-release metoprolol failed to reduce the restenosis rate following angioplasty in native coronary arteries.
Plasticity of Pax-5–/– Pre-B I Cells
Authors: Bruno Ludovica , Schaniel Christoph , Rolink Antonius
Published: April 2003

In Pax-5 deficient mice, B cell development is blocked at the pre-B I cell stage. In contrast to their wild type counterparts, Pax-5–/– pre-B I cells posses an extraordinary developmental plasticity showing hematopoietic stem cell features such as pluripotency and self renewing capacity. Here we review the in vitro and in vivo evidence of this intriguing phenomenon.
Activity Level and Balance in Subjects with Mild Alzheimer’s Disease
Authors: Pettersson Anna F. , Engardt Margareta , Wahlund Lars-Olof
Published: April 2003

To clarify if Alzheimer’s disease has an impact on activity level and postural control, we examined 17 elderly diagnosed with mild Alzheimer’s disease (MMSE scores 21–29) and 18 age- and gender-matched healthy controls (MMSE scores 27–30) using the Frenchay Activities Index, Bergs Balance Scale, Timed Up & Go and Walking in a Figure of Eight. Mild AD subjects were less active and had lower scores on Bergs Balance Scale, performed Timed Up & Go in longer time and took more steps outside the Figure of Eight, as compared to healthy elderly. This study shows that motor performance is affected already at mild stages of Alzheimer’s disease and also that functional performance other than gait may also be impaired.
Clinical Efficacy of Piracetam in Cognitive Impairment: A Meta-Analysis
Authors: Waegemans Tony , Wilsher Colin R. , Danniau Anne , Ferris Steven H. , Kurz Alexander , Winblad Bengt
Published: April 2003

A meta-analysis has been performed including nineteen double blind, placebo controlled studies with piracetam in patients suffering from dementia or cognitive impairment in the elderly. These studies had as common outcome measure a clinical global impression of change, a measure of clinically meaningful improvement. The meta-analysis of this global outcome followed the methodology set forward by the Cochrane Collaboration. This article describes the studies, the patient populations and the methods of data extraction. The results of the meta-analysis demonstrate a difference between those individuals treated with piracetam and those given placebo, both as significant odds ratio and as a favourable number needed to treat. While there may be problems in meta-analyses and the interpretation of the statistical results, the results of this analysis provide compelling evidence for the global efficacy of piracetam in a diverse group of older subjects with cognitive impairment.
Serum Folate Levels and Subsequent Adverse Cerebrovascular Outcomes in Elderly Persons
Authors: Maxwell Colleen J. , Hogan David B. , Ebly Erika M.
Published: April 2003

Recent epidemiologic studies have shown an association between low serum folate levels and risk of vascular disease, including stroke and various types of vascular cognitive impairment. We examined data from the Canadian Study of Health and Aging (CSHA), a population-based, prospective 5-year investigation of the epidemiology of dementia among Canadians aged 65+ years. The risk of an adverse cerebrovascular event (including vascular dementia, vascular cognitive impairment, or fatal stroke) during follow-up, was assessed according to serum folate quartiles among subjects with no evidence of dementia at baseline (n = 369). After adjusting for certain covariates, including cardiovascular disease and nutritional indices, education, smoking and baseline cognitive status, the risk estimate for an adverse cerebrovascular event associated with the lowest folate quartile compared with the highest quartile was OR 2.42 (95% CI 1.04–5.61). Results from stratified analyses also showed that relatively low serum folate was associated with a significantly higher risk of an adverse cerebrovascular event among female (OR 4.02, 95% CI 1.37–11.81) but not male (OR 1.02, 95% CI 0.25–4.13) subjects. Among the total sample, there was a consistent trend toward poorer health and cognitive outcomes during follow-up (including mortality, cognitive decline and dementia) among those in the lowest folate quartile compared with the highest quartile. Low serum folate levels are independently associated with a significantly higher risk of an adverse cerebrovascular event, including vascular dementia and stroke death, among older, cognitively vulnerable persons.
Effects of Insulin-Like Growth Factor I on Growth and Polyamine Metabolism in Various Organs in Rats
Authors: Höpfner M. , Berger A. , Fölsch U.R. , Löser C.
Published: April 2003

Background/Aim: Human insulin-like growth factor I (IGF-I) is known to be the mediator of growth hormone dependent proliferation and is responsible for growth-promoting effects in the gastrointestinal tract. Polyamines play an essential role in cell growth and differentiation. The aim of the present study was to investigate the growth-promoting potency of IGF-I in various organ systems simultaneously in rats and the potential role of the polyamine metabolism during IGF-I-induced gastrointestinal growth. Methods: Based on results of initial dose-response studies, male Wistar rats (150 g) were either treated by subcutaneous injections with (1) IGF-I (1 × 1,000 µg/kg/24 h); (2) IGF-I plus α-difluoromethylornithine (3 × 300 mg i.p./kg/24 h plus 2% in drinking water), a specific inhibitor of intracellular polyamine de novo synthesis, or (3) saline (controls). 9–10 animals per group were sacrificed after 5 days of treatment. Results: IGF-I caused a significant (p < 0.005) increase in the weight of small intestine and spleen due to hyperplasia in the small intestine and hypertrophy and hyperplasia in the spleen, while no trophic effects could be observed in stomach or pancreas. The amylase concentration in the pancreas was increased. Simultaneously administered α-difluoromethylornithine significantly (p < 0.005) abolished the IGF-I-induced trophic effects in small intestine and spleen. Conclusions: These data reveal different trophic effects of IGF-I in various organ systems: while significant growth stimulation was found in small intestine and spleen, no proliferation was seen in pancreas and stomach. Polyamines obviously play an important role in IGF-I-mediated gastrointestinal growth.
Hyperthermia Induces Multiple Pancreatic Heat Shock Proteins and Protects against Subsequent Arginine-Induced Acute Pancreatitis in Rats
Authors: Tashiro Mitsuo , Ernst Stephen A. , Edwards Julie , Williams John A.
Published: April 2003

Heat shock proteins (HSPs) which are induced by stress can provide protection against subsequent cellular damage. Whole body hyperthermia in rats leading to induction of HSP70 has been shown to protect against subsequent caerulein-induced acute pancreatitis. We studied the effect of hyperthermia on pancreatic HSP expression and found a significant increase in HSP70 (26.0-fold) and HPS27 (6.0-fold) but no change in HSP60, HSP90 or GRP78. Hyperthermia conferred significant protection against subsequent arginine-induced acute pancreatitis. More specifically, the degradation and disorganization of the actin cytoskeleton, an important early component of acute pancreatitis, was prevented. These results generalize previous work on caerulein-induced pancreatitis to another model of experimental pancreatitis, arginine-induced pancreatitis, and suggest that multiple HSPs may be involved in the cytoprotective effect in rat pancreas.
Survey on the Actual Status of Use of Antiseptics in Our Hospital
Authors: Matsubara Hajime , Togashi Atsuko , Takahashi Masaaki , Sagawa Kenichi , Shimada Shigehiko
Published: April 2003

Prevention of nosocomial infections is an important task for any medical institution. Although it is important to administer antibiotics prophylactically during the perioperative period, the proper use of antiseptics should have top priority. We carried out a survey to show the actual status of antiseptic use in our hospital in order to determine their proper use. The survey was carried out considering two aspects: the expense situation on the basis of the order slips and the status of use in each department and ward. It was conducted by questionnaire, and the pharmacist of each department asked questions to the nursing staff there. It was found that disinfectants and antiseptics are used almost correctly in our hospital. However, some improper uses were also found. In the future, on the basis of the findings of this study by questionnaire, we would like to give instructions from the standpoint of the pharmacist in the proper use of disinfectants and antiseptics and in the control of nosocomial infections.
Dendritic Cell-Based Immunoregulatory Strategies
Authors: Matsue Hiroyuki , Kusuhara Masahiro , Matsue Keiko , Takashima Akira
Published: April 2003

Dendritic cells (DC) are special subsets of professional antigen-presenting cells that play a dual role in initiating and silencing acquired immune responses. Thus, it should be feasible to control the magnitude and direction of immune responses by experimental manipulation of DC function. We will provide an overview of the recent progress in the development of DC-based immunostimulatory and immunosuppressive strategies, which are potentially applicable to the treatment of cancer, allergy, autoimmune disease, allograft rejection and graft versus host disease.
Sensitization of Mice with Olive Pollen Allergen Ole e 1 Induces a Th2 Response
Authors: Batanero Eva , Barral Patricia , Villalba Mayte , Rodríguez Rosalía
Published: April 2003

Background: Olive pollen is one of the main causes of allergy in Mediterranean countries, where it is widely distributed. One inconvenience in studying new immunotherapies for olive pollen allergy is the lack of suitable animal models. The aim of this study was to develop a murine model of IgE sensitization to Ole e 1, the major allergen of olive pollen, which mimics the immunological features of olive pollinosis in humans and to investigate the in vivo antigenicity of the recombinant form of the allergen. Methods: BALB/c mice were sensitized by intraperitoneal administration of natural Ole e 1 (nOle e 1) and recombinant Ole e 1 (rOle e 1) in Al(OH)3, respectively. Serum levels of specific IgE, IgG1 and IgG2a, cytokine production and the proliferative response of splenocytes after in vitro stimulation with nOle e 1 were analyzed by ELISA and flow cytometry. The binding capacity of rOle e 1-specific IgG1 was examined by ELISA and immunoblotting. Results: Sensitization with nOle e 1 or rOle e 1 induced high levels of specific IgE and IgG1 versus low IgG2a antibody levels. Splenocytes from sensitized mice exhibited a proliferative response to nOle e 1. In vitro stimulated splenic cells from nOle e 1-primed mice produced IL-4 and low or nondetectable levels of IFN-γ. Specific IgE and IgG1 antibodies of immunized mice bound to the same Ole e 1 isoforms and showed a similar degree of cross-reactivity as observed for human IgE. Mouse specific nOle e 1 IgG1 was strongly inhibited by IgE from allergic patients. The IgG1 antibodies elicited by rOle e 1 reacted with both the recombinant and natural forms of the allergen. Conclusions: A murine model of Ole e 1 sensitization has been established. rOle e 1 shows similar allergenicity and antigenicity to its natural form. This model should provide a useful tool for evaluating antigenic molecules and exploring new therapeutic approaches in order to treat IgE-mediated olive pollinosis.
Detection of Novel CD Antigens on the Surface of Human Mast Cells and Basophils
Authors: Ghannadan Minoo , Hauswirth Alexander W. , Schernthaner Gerit-Holger , Müller Michael R. , Klepetko Walter , Schatzl Georg , Sperr Wolfgang R. , Bühring Hans-Jörg , Valent Peter
Published: April 2003

Background: Mast cells (MC) and basophils are effector cells of allergic reactions. Growth and function of these cells are regulated by a network of cytokines, other ligands, and respective cell surface membrane receptors. Methods: In the present study, we examined the expression of novel CD antigens on human lung MC, skin MC, blood basophils, the MC line HMC-1, and the basophil cell line KU-812. Expression of surface antigens was analyzed by monoclonal antibodies (mAbs) and indirect immunofluorescence staining techniques. Results: Primary MC were found to react with mAbs against KIT (CD117), the signal regulatory protein SIRP-α (CD172a), and the ectoenzyme E-NPP3 (CD203c). Human basophils were found to express large amounts of E-NPP3 and lower levels of Siglec-5 (CD170), CXCR4 (CD184) and SIRP-α. The HMC-1 cell line was recognized by mAbs against SIRP-α, CXCR4, endothelial protein C receptor (CD201) and E-NPP3. KU-812 cells were found to react with mAbs against E-NPP3, CXCR4 and glycophorin C (CD236R), but did not react with mAb against endothelial protein C receptor. Most of the other CD antigens tested disclosed negative results. Conclusions: In summary, our data provide further evidence that MC and basophils express a unique composition of surface antigens. The use of novel CD antibodies may help to isolate MC and basophils and to study their functional properties.
Sulphorhodamine-B-Labelled Albumin Uptake around the Ostium of the Renal Artery in Rabbits: Changes with Age
Authors: Murphy Christopher L. , Lever M. John
Published: April 2003

Because protein transport between blood and artery wall is important in atherogenesis, we have measured the uptake of fluorescently labelled albumin around the aorto-renal branch, an important site for lesions. Tracer concentrations in artery wall sections were quantified using digital fluorescence microscopy. Short-term experiments indicated endothelial permeability, while longer ones indicated the steady-state distribution of native proteins within the wall. In sexually immature rabbits (65–75 days), the permeability of the aorta was greater downstream of the renal ostium than upstream (p < 0.004). However, in mature rabbits (120–156 days), the permeability was greater, on average, at the upstream site compared to downstream. This change in pattern of uptake around the renal ostium with age appears to be due to increased uptake at the upstream site in mature animals, which was over fourfold greater than that measured at the equivalent site in immature animals (p < 0.01). In the renal artery itself, permeability was low and age independent. In mature animals, endothelial permeability did not correlate with steady-state wall concentrations, suggesting that the latter may be more dependent upon the rate of exit of protein and/or available space in the wall, rather than the rate of entry. The age-dependent changes in the spatial pattern of permeability correspond to the different distributions of spontaneous lipid accumulation in immature and mature vessels of both rabbits and humans, implying that permeability of the wall is important in atherogenesis.
Altered Dye Diffusion and Upregulation of Connexin37 in Mouse Aortic Endothelium Deficient in Connexin40
Authors: Krüger Olaf , Bény Jean-Louis , Chabaud Fabienne , Traub Otto , Theis Martin , Brix Klaudia , Kirchhoff Susanne , Willecke Klaus
Published: April 2003

Connexin40 (Cx40), connexin37 (Cx37) and connexin43 (Cx43) are subunit proteins of gap junction channels in the vascular wall which are presumably involved in the propagation of vasomotor signals. In this study we have investigated in Cx40-deficient versus wild-type aortic endothelium to which extent loss of Cx40 impairs intercellular communication. We show in Cx40-deficient mice that expression of both Cx37 and Cx43 protein was increased approximately 3- and 2-fold over the level in wild-type endothelium, respectively. Furthermore, Cx37 immunosignals were distributed more homogeneously on contacting plasma membranes in Cx40-deficient versus with wild-type endothelium. Cx43 was not detected in endothelium but only in smooth muscle cells of the vessel wall. Iontophoretic injection of Lucifer Yellow or neurobiotin into aortic endothelium of Cx40-deficient mice showed extensive intercellular transfer of neurobiotin but not of Lucifer Yellow. In contrast, intercellular spreading of Lucifer Yellow was observed in endothelium of wild-type aorta. As shown by electron microscopy, gap junctions in Cx40-deficient endothelium were morphologically different from those of wild-type vessels. These results demonstrate that dye diffusibility of endothelial gap junctions is different in Cx40-deficient and wild-type mice, although Cx40-deficient mice retain the capability of intercellular communication. Apparently, Cx40-deficient endothelial cells upregulate and redistribute Cx37 as a molecular adaptation to the lack of Cx40.
A Comparison of Side Effects of Levofloxacin to Other Agents Concerning the Ecological and Microbiological Effects on Normal Human Flora
Authors: Acar Jacques F.
Published: April 2003

The safety of levofloxacin was compared to that of non-fluoroquinolone alternatives used for respiratory tract infections. Results from five randomised controlled trials revealed that the incidence of any adverse events possibly associated with levofloxacin ranged from 5.8% to 22.7%, whereas that of comparators (ceftriaxone, cefuroxime axetil, clarithromycin and amoxicillin–clavulanic acid) ranged from 8.5% to 39.3%. The rate of adverse drug reactions (ADRs) was lower for levofloxacin in all trials. The most common adverse events for all agents tended to be gastrointestinal in nature. Levofloxacin was associated with a mild effect on the normal microflora, reaching a maximum at four days of therapy, with complete recovery being achieved by seven days post-therapy. No colonisation with resistant strains was observed during the period of levofloxacin therapy. Amoxicillin–clavulanic acid administration selected for resistant strains of Enterobacteriaceae, and ampicillin administration was associated with both resistant strains of Enterobacteriacae as well as Candida spp. Ceftriaxone selected resistant strains of Clostridium difficile and Candida spp. Thus, microflora effects favoured levofloxacin over all of the agents tested, including macrolides and tetracyclines. These results confirm that the ecological impact of levofloxacin is markedly less than that associated with non-fluoroquinolone comparators.
Systemic Inflammation, Endothelial Dysfunction, Dietary Fatty Acids and Micronutrients as Risk Factors for Stroke: A Selective Review
Authors: Feigin Valery L. , Anderson Craig S. , Mhurchu Cliona Ni
Published: April 2003

As medicine moves into the 21st century, with added pressures of increasing costs and limited resources, successful reduction of the impact of stroke on the population will require shifting our emphasis away from treating end stages of generalized atherosclerosis and other underlying diseases to prevention of these diseases. However, before any potential interventions can be promoted with confidence, more needs to be known about the specific causes of stroke subtypes in various populations, especially potentially modifiable risk factors. In this selective review, we appraise current evidence on some markers of systemic inflammation (C-reactive protein), endothelial dysfunction (homocysteine, von Willebrand factor), dietary fatty acids and micronutrients as risk factors for stroke. Although a great deal of research into the role of these risk factors in cardiovascular diseases has been undertaken, little reliable information is available on their role in stroke, especially in the elderly. Evaluation of plasma fatty acids and specific antioxidants and micronutrients as well as markers of systemic inflammation, endothelial dysfunction (including C-reactive protein, homocysteine levels, von Willebrand factor, and paraoxonase activity) may prove to be valuable in the future determination of the risk of stroke.
Improvement in Stroke Quality Management by an Educational Programme
Authors: Behrens Stephan , Daffertshofer Michael , Interthal Cordula , Ellinger Klaus , van Ackern Klaus , Hennerici Michael
Published: April 2003

Time after symptom onset in ischaemic stroke has to be as short as possible to increase success of treatment. We prospectively analysed latencies from symptom onset until the start of therapy and the rate of thrombolysis in 196 patients with suspected stroke sequentially admitted to the hospital before (6 weeks prior, n = 83) and after (n = 113) initiating an educational stroke programme (EP). A total of 345 dispatchers, paramedics, and emergency staff were trained, each person for at least 2 h. The mean pre-hospital time interval from symptom onset until admission was significantly decreased by nearly 2 h (p < 0.05). Thrombolytic therapy frequencies increased from 2 to 10.5% (p < 0.01) because the overall mean time interval from admission to the start of therapy significantly decreased (p < 0.01) by 69 min after the EP, with increasing numbers of patients suitable for acute stroke therapies within a 0- to 3-hour treatment window.
Have Oral Contraceptives Reduced the Prevalence of Acne? A Population-Based Study of Acne vulgaris, Tobacco Smoking and Oral Contraceptives
Authors: Jemec Gregor B.E. , Linneberg Allan , Nielsen Niels Henrik , Frølund Lars , Madsen Flemming , Jørgensen Torben
Published: April 2003

Background: The prevalence of acne among adolescents appears to vary geographically. This study was therefore undertaken to describe the prevalence rate of acne among Danish adolescents and to study the possible influence of oral contraceptives (OC) and tobacco smoking on disease prevalence and severity. Both have been suggested to influence acne and are therefore potential confounders in studies of acne prevalence. Methods: A random sample of 186 15- to 22-year-old subjects participating in a population-based study of allergic diseases in Copenhagen County were also examined for acne. Questionnaire data on demographic variables, acne problems, smoking status and use of OC were recorded, and acne was graded according to the Leeds scale. Results: The prevalence of clinical acne (Leeds score >1) was 40.7% for men and 23.8% for women (odds ratio, OR, acne vs. no acne: 0.46, 95% confidence interval, CI: 0.24–0.85). Acne was perceived as a personal problem by 37.6% of all subjects, and this was associated with clinical acne (OR: 5.5, 95% CI: 2.7–10.9). The use of OC was associated with a significantly lower prevalence of acne (OR: 0.32, 95% CI: 0.11–0.86), while the use of tobacco smoking was not significantly associated with acne (OR: 0.54, 95% CI: 0.17–1.78). Conclusion: In congruence with recent reports from other countries, the prevalence rate of acne among adolescents was found to be lower than previously described in older reports. In this population, the use of OC was associated with a lower prevalence of acne.
Use of Sunscreens in Families Living in Switzerland
Authors: Berret Joël , Liardet Stéphanie , Scaletta Corinne , Panizzon Renato , Hohlfeld Patrick , Applegate Lee Ann
Published: April 2003

Background: The hazards due to sun exposure are well known. Many recent studies have emphasized the protection against the harmful effects of the sun by the use of sunscreens and, moreover, by staying in the shade and wearing long-sleeved shirts, hats and sunglasses. Switzerland has one of the highest rates of skin cancer induction in Europe and the incidence of melanoma in Switzerland is constantly increasing with an incidence of 10–12/100,000 inhabitants/year. Interestingly, some studies have evoked the possibility that sunscreen use can increase the risk of melanoma by increasing overall sun exposure. Objective and Methods: In this context, the aim of our study was to estimate the amount of sun exposure of children, and their parents, living in Switzerland and to give a description of how they protect themselves against sun irradiation. Questionnaires were provided to pediatricians in every state (canton) in Switzerland and were given to families coming for consultation. Results: A total of 328 forms including 1,285 individuals were returned from most of the cantons in Switzerland. The majority of the Swiss families had 2 children under 16 years of age with middle-aged parents (30–45 years) and a central European skin type (light skin of type II–III, brown or blue eyes, and brown to blond hair). An important sun exposure was noted even though the population seems to be conscious of the associated dangers. Sunscreens were the first-line defense against sun exposure with clothing and shielding oneself from the sun not being highly used. Moreover, sunscreens tended to be misused with most people applying them at the beach or swimming pool (instead of 15 min before exposure) and few applications throughout the day. Conclusions: Prevention should imperatively be emphasized for lower overall sun exposure as sunscreens are primarily used at the beach and not in routine daily exposure. In addition, it is agreed that prevention campaigns would be better directed towards children because up to 80% of detrimental sun exposure occurs during childhood.
Does Lumbar Cerebrospinal Fluid Reflect Ventricular Cerebrospinal Fluid? A Prospective Study in Patients with External Ventricular Drainage
Authors: Sommer Jan B. , Gaul Charly , Heckmann Josef , Neundörfer Bernhard , Erbguth Frank J.
Published: April 2003

Ventriculitis may sometimes occur after an external ventricular drain has been removed, and diagnosis has to be made by lumbar puncture. But are the lumbar findings comparable to previously obtained ventricular results? In a prospective study, sample pairs of ventricular and lumbar cerebrospinal fluid (CSF) were obtained at an interval of <30 min in 25 patients with increased intracranial pressure suffering from cerebral hemorrhage (n = 15), meningitis/encephalitis (n = 6), cerebral infarction (n = 3), and meningeosis carcinomatosa (n = 1). CSF was analyzed for protein, albumin, IgG, IgA, IgM, glucose, lactate, and leukocytes including cytological differentiation. A significant ventriculo-lumbar increase was observed for protein, albumin, and the immunoglobulins. Lactate was distributed equally in ventricular and lumbar CSF, as well as glucose in the cerebral hemorrhage subgroup (n = 15). Cell count failed to show a clear ventriculo-lumbar ratio. Cytological distribution was comparable in lumbar and ventricular CSF, except for macrophages showing a significant rostrocaudal decrease. In conclusion, in cases of clinically suspected bacterial central nervous system infection after removal of an external ventricular drain, lumbar CSF lactate, glucose, and cytology are comparable to previously determined ventricular values, and thus may help physicians to choose the best treatment.
Construction of a Confidence Set of Markers for the Location of a Disease Gene Using Affected Sib Pair Data
Authors: Lin Shili
Published: April 2003

We have previously proposed a confidence set approach for finding tightly linked genomic regions under the setting of parametric linkage analysis. In this article, we extend the confidence set approach to nonparametric linkage analysis of affected sib pair (ASP) data based on their identity-by-descent (IBD) information. Two well-known statistics in nonparametric linkage analysis, the Two-IBD test (proportion of ASPs sharing two alleles IBD), and the Mean test (average number of alleles shared IBD in the ASPs), are used for constructing confidence sets. Some numerical analyses as well as a simulation study were carried out to demonstrate the utility of the methods. Our results show that the fundamental advantages of the confidence set approach in parametric linkage analysis are retained when the method is generalized to nonparametric analysis. Our study on the accuracy of confidence sets, in terms of choice of tests, underlying disease incidence data, and amount of data available, leads us to conclude, among other things, that the Mean test outperforms the Two-IBD test in most situations, with the reverse being true only for traits with small additive variance. Although we describe how to construct confidence sets based on only two familiar tests, one can construct confidence sets similarly using other allele sharing statistics.
Association of Galectin-9 with Eosinophil Apoptosis
Authors: Saita Naoki , Goto Eisuke , Yamamoto Taro , Cho Isamu , Tsumori Kaori , Kohrogi Hirotsugu , Maruo Keishi , Ono Tomomichi , Takeya Motohiro , Kashio Yumiko , Nakamura Kazuhiro , Hirashima Mitsuomi
Published: April 2003

Background: There is no information whether galectin-9 (a novel eosinophil chemoattractant) was associated with pathogenesis of eosinophilic disorders. Methods: We assessed the expression of galectin-9 with imunostaining and in situ hybridization both in the lesion of angiolymphoid hyperplasia with eosinophilia, and peripheral blood eosinophils of eosinophilic patients (E-Eos) in comparison with those of normal volunteers (N-Eos). Regulation of expression of galectin-9 on eosinophils and the effect of galectin-9 on apoptosis of eosinophil were also evaluated. Results: Many eosinophils infiltrating the site were positive for galectin-9. Surface and intracellular immunoreactive galectin-9 was more evident in E-Eos than N-Eos. When eosinophils were cultured with IL-5 in vitro, the surface galectin-9 expression of E-Eos was significantly downregulated, although that of N-Eos was not affected. Treatment of eosinophils with dexamethasone or anti-Fas antibody significantly upregulated the surface galectin-9 expression of E-Eos. In contrast, dexamethasone partially downregulated the surface galectin-9 of N-Eos, although anti-Fas antibody failed to affect on the surface galectin-9 expression. We also found that recombinant galectin-9 significantly suppressed apoptosis of E-Eos (p = 0.0431), whereas it apparently enhanced apoptosis of N-Eos (p = 0.0173). Furthermore, dexamethasone-induced apoptosis of N-Eos was significantly suppressed by galectin-9 (p = 0.0431), whereas galectin-9 failed to induce significant change in dexamethasone-induced apoptosis of E-Eos. In contrast, apoptosis induced by anti-Fas antibody in both N-Eos (p = 0.0431) and E-Eos (p = 0.0431) was enhanced by galectin-9. Conclusions: These findings suggested that galectin-9 was produced by eosinophils, and galectin-9 showed heterogeneous effects and kinetics to eosinophils, and this factor might be one of crucial factors in eosinophilic inflammation.
Histopathology of Biocompatible Hydroxylapatite-Polyethylene Composite in Ossiculoplasty
Authors: Meijer Astrid G.W. , Segenhout Hans M. , Albers Frans W.J. , van de Want Han J.L.
Published: April 2003

The biocompatibility of hydroxylapatite-polyethylene composite implants (HAPEX, Smith and Nephew) was investigated in this study. Eleven middle ear prostheses, removed during revision surgery, have been examined by light microscopy, transmission electron microscopy and scanning electron microscopy. The results show that the middle ear prostheses become overgrown by fibrous tissue inside a thin epithelial layer. In some cases the prosthesis is covered by fibrous tissue without an outer layer of epithelial cells. No arguments have been found for the accumulation of macrophages and foreign body giant cells associated with a foreign body reaction to the material. Therefore, hydroxylapatite-polyethylene composite implants (HAPEX, Smith and Nephew) would seem to be very suitable for reconstructive middle ear surgery.
Molecular Diagnosis of Deafness: Impact of Gene Identification
Authors: Usami Shin-ichi , Koda Eiko , Tsukamoto Koji , Otsuka Akihiro , Yuge Isamu , Asamura Kenji , Abe Satoko , Akita Jiro , Namba Atsushi
Published: April 2003

Recent progress in identifying genes responsible for hearing loss enables the ENT clinician to apply molecular diagnosis by genetic testing. This article focuses on three genes, which are prevalent and therefore commonly encountered in the clinic. GJB2 (connexin 26) is currently recognized as the most prevalent gene responsible for congenital hearing loss in many countries. A series of reports revealed that different combinations of GJB2 mutations exist in different ethnic populations, indicating that ethnic background should be considered when performing genetic testing. GJB2 mutations will be of particular interest in combination with universal infant hearing screening programs, because it has been shown that early identification of hearing loss and early intervention are crucial for language development. Progress in genetic analysis has changed the concept of diseases. The present review introduces the example of two historically distinct categories of disease, Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct, which are currently considered to be a continuum of diseases caused by the same gene, PDS. This review also emphasizes that some hearing impairment can be prevented. The 1555A→G mitochondrial mutation, the most prevalent mitochondrial mutation found in the hearing-impaired population, was found in approximately 3% of the outpatients. The 1555A→G mutation is known to be associated with a susceptibility to aminoglycoside antibiotics. There may be a considerably large high-risk population and to avoid possible side effects in this group, a rapid mass screening system and careful counseling are recommended.
Analysis of Mixed Chimerism in Patients after Allogeneic Stem Cell Transplantation Using a Capillary Electrophoresis System
Authors: Tsutsumi Y. , Tanaka J. , Kato N. , Zhang L. , Mori A. , Kobayasi R. , Kasai M. , Asaka M. , Imamura M.
Published: April 2003

We analyzed mixed chimerism (MC) after allogeneic stem cell transplantation (SCT) using a capillary electrophoresis system with four kinds of fluorescence-labeled primers for microsatellites (D3S1359, D6S89, ACTBP2, HGH). The sensitivities of all microsatellites were at least 3%. The present method is sufficiently rapid: only 3–4 h are needed to perform all the procedures. For analysis of MC in 30 patients who had undergone allogeneic SCT, heterozygosity of all microsatellites was over 88% and informativeness of ACTBP2 and HGH was over 73%. We analyzed MC using this technique to determine whether it was useful for prediction of the prognosis of 22 patients who had undergone allogeneic SCT. MC was more frequently observed in patients who were treated without total body irradiation (TBI) than in patients who were treated with TBI (p = 0.009). MC was also seen in a larger percentage of patients without acute graft-versus-host disease (p = 0.027). Six patients developed graft failure or relapse among 12 patients with MC. The graft failure or relapse was higher in patients with MC than in patients with complete chimerism (CC) (p = 0.009) especially if they were over 30 years of age (p = 0.0005). In contrast, graft failure or relapse was not higher in patients with MC compared with patients with CC under 30 years of age (p = 0.78). These results show that MC is an important predictive factor, especially in patients over 30 years of age.
Candidate Gene Association Studies in Sporadic Alzheimer’s Disease
Authors: Combarros O. , Alvarez-Arcaya A. , Sánchez-Guerra M. , Infante J. , Berciano J.
Published: April 2003

The genetics of Alzheimer’s disease (AD) is complex. Three genes (amyloid precursor protein, presenilin 1 and presenilin 2) have been described in the relatively rare, early-onset, autosomal dominant familial form of AD. In the common, non-familial (sporadic) late-onset AD, the major known genetic risk factor is the Ε4 allele of the apolipoprotein E (APOE) gene. However, at least half of the people who develop AD do not carry this allele, and not all people who do carry this allele develop AD even if they live to an old age. Therefore, approximately 30 other candidate genes involving a protein in a critical pathway in the pathogenesis of disease (principally interaction with amyloid-β, oxidative stress and inflammation/apoptosis) have been considered as risk factors for sporadic AD. Then these genes have been sequenced in search of genetic variability or polymorphisms, and each putative polymorphism has been reported to alter the risk of AD either directly or by an interaction with the APOE Ε4 allele. However, positive-association studies with these candidate genes have not been consistently confirmed.