bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronological Relationship between Antisocial Personality Disorder and Alcohol Dependence
Authors: Bahlmann M. , Preuss U.W. , Soyka M.
Published: April 2003

Personality disorders, and particularly antisocial personality disorder (ASPD), frequently co-occur with alcohol dependence. ASPD is considered to be an important cofactor in the pathogenesis and clinical course of alcohol dependence. The chronological relationship between the onset of symptoms of ASPD and alcohol-dependence characteristics has not yet been studied in great detail and the role of ASPD in classification schemes of alcohol dependence as suggested by Cloninger and Schuckit has yet to be determined. We studied 55 alcohol-dependent patients to assess the prevalence and age at manifestation of ASPD, conduct disorder characteristics as well as alcohol dependence by employing the Semi-Structured Assessment for the Genetics of Alcoholism and the Structured Clinical Interview for DSM-III-R. Results indicate that the onset of ASPD characteristics precede that of alcohol dependence by some 4 years. This finding suggests that in patients with ASPD, alcohol dependence might be a secondary syndrome as suggested by previous research.
Speech Perception in Nucleus CI24M Cochlear Implant Users with Processor Settings Based on Electrically Evoked Compound Action Potential Thresholds
Authors: Smoorenburg Guido F. , Willeboer Christina , van Dijk Johannes E.
Published: April 2003

Adjusting the speech processor of a cochlear implant, per electrode, to the individual’s response is a laborious task that may interfere with a user-friendly start of implant-mediated hearing, particularly in children. This research concerns the possibility of processor adjustment based on a profile derived from measurements of the electrically evoked compound action potential (ECAP) thresholds across the electrode array, followed by adjustment of the overall level of the profile to the hearing threshold and maximum comfortable loudness level using live voice. The results for CVC word lists show that speech perception is quite insensitive to the threshold setting of the speech processor. On average, the speech score does not decrease by more than 10% when, with the new method, the threshold setting comes out so much lower that the dynamic range has doubled. In contrast, the speech score appears to be sensitive to an increase of the maximum high-frequency stimulation settings for the basal electrodes, resulting in lower scores at these higher settings. The correlation between the overall ECAP thresholds and conventionally measured subjective thresholds is weak (r = 0.64). However, the correlation between the slopes of these threshold curves is satisfactory (r = 0.82). The correlation between the ECAP thresholds and the maximum stimulation levels is poor, both with respect to overall level and slope (r = 0.39 and 0.36, respectively). Applicability of the ECAP threshold in processor adjustment could not be demonstrated in this study. Prediction of the most critical factor in speech perception, the slope of the maximum stimulation curve, from the ECAP thresholds is poor. However, considering habituation to the initial processor setting of at least 6 months, the small decrease in the CVC scores with the new setting suggests that a more user-friendly adjustment procedure can be developed.
A Novel Vestibular Approach for Gene Transfer into the Inner Ear
Authors: Praetorius Mark , Knipper Marlies , Schick Bernhard , Tan Justin , Limberger Annette , Carnicero Estela , Alonso Maria Teresa , Schimmang Thomas
Published: April 2003

The aim of gene transfer to the cochlea and vestibular organ is to protect the inner ear from different disorders. Although various vectors for gene delivery have been used with some success, there remains a need for a reliable transfer of genes into the inner ear without damaging cochlear function. Here, we have tested a novel application method for gene transfer into the rat inner ear in vivo using herpes simplex virus type-1(HSV-1)-based amplicon vectors. Our goal was to find an entry route into the inner ear that leaves its function intact. Besides other non-invasive and invasive application techniques, we applied the viral vector via injection through a small opening of the utriculus. Using this method, efficient β-galactosidase reporter gene expression was achieved in nearly all neurons in the vestibulum and cochlea, without functional hearing deficits. At the time point of maximal expression 5 days after injection, β-galactosidase activity was also observed in axonal fibres and synaptic endings close to inner and outer hair cells. Our results thus describe an efficient and reliable protocol for short-term expression of potential therapeutic genes in the neuronal compartment of the inner ear.
Effects of Prolonged Occlusion on Stratum corneum Barrier Function and Water Holding Capacity1
Authors: Fluhr J.W. , Lazzerini S. , Distante F. , Gloor M. , Berardesca E.
Published: April 2003

Purpose of the Study: We aimed to evaluate whether prolonged occlusion can induce stratum corneum barrier damage, alterations in stratum corneum hydration or water-holding capacity (WHC) lasting longer than the occlusion time. Materials and Methods: 12 subjects were occluded on the forearm for 24, 48, 72 and 96 h. Two hours after occlusion removal, transepidermal water loss (TEWL) and skin hydration were measured and a sorption-desorption test performed. Results: TEWL showed an increase reaching a plateau on day 2. Hydration and WHC did not show significant changes. Hygroscopicity showed the highest level on day 1, decreasing during the following days. A highly significant correlation between capacitance values and the WHC could be detected (p < 0.0001, r = 0.8206). No correlation could be detected between hygroscopicity and TEWL. Conclusions: Prolonged occlusion induces barrier damage without skin dryness. Occlusion also induces an increased hygroscopicity. A correlation between these two findings could not be proven.
Postural Skin Colour Changes during the Corticosteroid Blanching Assay
Authors: Henry F. , Fumal I. , Piérard G.E.
Published: April 2003

Objective: To assess the effect of the position of a limb (dependency) on the cutaneous vasoconstrictor (blanching) assay (VCA) using topical corticosteroid preparations. Method: Two studies were performed on the forearms of healthy volunteers using tristimulus reflectance colorimetric assessments. The first one conducted in 60 normal adults aimed at quantifying the range of variation in the skin chromaticity a* when the arm was successively positioned horizontally and vertically, either in the upward or downward direction. In the second study, 16 volunteers were selected according to a weak spontaneous postural dependency of the limb in a* (<2 units). The blanching effect of 0.1% mometasone furoate, 0.1% betamethasone valerate and petrolatum were compared to the colour of an untreated site. Chromaticity a* and the colorimetric variable (ΔtL*2 + Δta*2)0.5 were measured in time following a 2-hour application. Results: The postural variations in skin colour varied among subjects. The majority of them (80%) presented a difference in a* higher than 2 units between the upright and downward arm positions. The upright position appeared to be the most sensitive to show significant differences in the VCA. Mometasone furoate exhibited the most prominent effect, significantly higher than betamethasone valerate and controls. Conclusion: The corticosteroid VCA is influenced by the position of the limb. The upright position increases the sensitivity of the test. Mometasone furoate is more potent than betamethasone valerate.
Identity Constraints: The Perceived Structural Requirements of a 'Good' Identity
Authors: Schachter Elli P.
Published: April 2003

Ego Identity Status Theory, following Erikson''s identity theory, describes mature identity as striving towards sameness and continuity, and as thus constrained by structural elements such as closure, consistency and commitment. Lately, however, theoreticians are portraying a relatively unconstrained postmodern, mutable, multiple, Protean self, continuously changing and inconsistent across situations. This paper examines personal narratives of identity formation in order to determine what 30 Jewish modern orthodox young adults implicitly considered to be the structural requirements of a ''good'' identity. Their deliberations regarding a potentially conflictual identity issue (i.e. their religious and sexual development) revealed four constraints on identity: A ''good'' identity must allow for: a sense of consistency, sameness and continuity; the inclusion of all significant identifications; mutual recognition between individual and society; and feelings of authenticity and vitality. The possible implications of the concept of ''identity constraints'' on identity theory are discussed.
The Efficacy of Medical and Surgical Treatment of Endometriosis-Associated Infertility and Pelvic Pain
Authors: Donnez Jacques , Squifflet Jean , Pirard Céline , Jadoul Pascale , Wyns Christine , Smets Mireille
Published: April 2003

This article is a review of the efficacy of medical and surgical treatment of endometriosis-associated infertility and pelvic pain. Endometriosis is the cause of pelvic pain (dysmenorrhea, dyspareunia) and infertility in more than 35% of women of reproductive age. Complete resolution of endometriosis is not yet possible but therapy has essentially three main objectives: (1) to reduce pain; (2) to increase the possibility of pregnancy; (3) to delay recurrence for as long as possible. It could be concluded that a consensus will probably never be reached on minimal and mild endometriosis. Nevertheless, because the Canadian study reported a large number of cases, we strongly support the view that visible endometriosis must be removed at the time of surgery. In cases of moderate and severe endometriosis-associated infertility, the combined approach (operative laparoscopy with GnRH-a) must be considered as ‘first-line’ treatment. The mean pregnancy rate of 50% reported in the literature following surgery provides scientific proof that operative treatment should be undertaken first to give our patients the best chance of conceiving naturally.
Effect of Relaxin in Two Models of Renal Mass Reduction
Authors: Garber Sandra L. , Mirochnik Yelena , Brecklin Carolyn , Slobodskoy Leonid , Arruda Jose A.L. , Dunea George
Published: April 2003

Background: Relaxin (Rlx), a 6-kD protein hormone, belongs to the insulin growth factor family. We have previously shown that Rlx reduces interstitial fibrosis in a model of chronic papillary necrosis. Hypothesis: The purpose of this study was to extend these observations to a model of renal injury induced by mass reduction. Material and Methods: Renal mass was reduced by either infarction or surgical excision of both poles, with removal of the contralateral kidney. Two weeks later, creatinine clearance was done and animals from both groups implanted with osmotic pumps delivering either Rlx (2 µg/h) or vehicle (Veh). Treatment was continued for 4 weeks. The severity of the glomerular injury was quantified by planimetric measurements. Renal function was assessed by creatinine clearance and plasma creatinine. Results: Rlx significantly decreased systolic blood pressure in animals with infarction. This was accompanied by a decrease in serum creatinine and a slight improvement in creatinine clearance. The severity of the glomerular lesion was reduced by Rlx (sclerosis index, Veh 1.16 ± 0.13 vs. Rlx 0.74 ± 0.16, p = 0.037). In the excision group the animals were normotensive. In this group, Rlx treatment was accompanied by a decrease in serum creatinine (Veh 1.01 ± 0.03 vs. Rlx 0.81 ± 0.05 mg/dl, p = 0.02) and an increase in GFR (Veh 0.90 ± 0.14 vs. Rlx 1.33 ± 0.11 ml/min, p = 0.03). The sclerosis index was also reduced. Conclusion: Rlx decreases renal injury by at least two mechanisms, one by lowering blood pressure as seen in the infarction model, the other independent of blood pressure as seen in the normotensive excision model where there was also a significant functional improvement.
Understanding Inherited Disease through Human Migrations: A South-West Asian Perspective
Authors: McElreavey K. , Quintana-Murci L.
Published: April 2003

Mitochondrial DNA (mtDNA) and the Y chromosome are inherited in a haploid manner and have been used extensively to reconstruct human lineages. mtDNA and the majority of the Y chromosome lack recombination and show high rates of apparently neutral mutation. Here, we demonstrate how detailed analysis of these uniparental inherited markers can reveal general and more subtle population movements within south-west Asia. These include a major migration of modern humans from East Africa to western and southern Asia around 60,000 YBP, migrations of populations from the Fertile Crescent in south-western Iran to India approximately 8,000 YBP, and migrations of Indo-European speakers from Central and West Asia to India approximately 5,000 YBP. We highlight how the understanding of these, and other population movements, can be useful in tracing the dispersal of disease-causing mutant alleles, and how these data could be applied to predicting the segregation of mutant alleles within populations.
Effects of Irritability on Craving before and after Cue Exposure in Abstinent Alcoholic Inpatients: Experimental Data on Subjective Response and Heart Rate
Authors: Chiang Sonnig S.W. , Schuetz Christian G. , Soyka Michael
Published: April 2003

Objective: Irritability is often linked with problem drinking. The aim of this study is to examine the possible influence of irritability on craving induced by a cue-exposure paradigm. Methods: 30 male abstinent alcoholic inpatients of the Psychiatric Hospital of Munich University, Germany gave answers to a series of personality questionnaires. Results of this study concerning the impact of aggressivity on craving for alcohol has recently been published. In this study, the subjects were subdivided into a low- and a high-irritable group based on their scores on the irritability subscale of the Buss-Durkee Hostility Inventory and were exposed to alcohol cues. Craving was measured by means of the Alcohol Craving Questionnaire (ACQ) and Visual Analogue Scales (VAS). The heart rate was also assessed throughout the whole process. ANCOVA for repeated measurement was employed to evaluate the data – irritability disposition as the between-subject factor and the experimental manipulation (absence vs. presence of alcohol cues) as the within-subject factor. Results: Major findings are: (1) main effects of irritability on ‘emotionality’, ‘purposefulness’, and ‘expectancy’ of the ACQ as well as on ‘craving for alcohol’ of the VAS were significant; (2) cue exposure also exerted a significant main effect on ‘craving for alcohol’ of the VAS and on the heart rate after the presentation of alcohol cues; (3) on ‘compulsivity’ of the ACQ and ‘intention to alcohol intake’ of the VAS; there was a significant interaction between irritability and cue exposure. The high-irritable alcoholics, compared with their statements in the baseline, tended to report a higher control over alcohol intake and a lower intention to alcohol use after cue exposure. However, after confrontation with alcohol stimuli, their low-irritable counterparts reported a much lower control and a slightly higher intention than they did in the baseline. Conclusions: The results of this study indicate that induced craving in hospitalized alcohol addicts probably varies with the magnitude of their irritability; it might make patients more aware of their vulnerability to alcohol, help them develop more differential coping strategies and improve medical therapy against alcohol craving.
Effects of Opipramol as an Evening Anaesthesiologic Premedication
Authors: Gerlach Klaus , Uhlig Thomas , Plathof Jasmin , Klassen Andre , Stoll Klaus-Dieter , Schmucker Peter , Hueppe Michael
Published: April 2003

To date, opipramol has not been examined within the context of evening premedication in anaesthesiology. A suitable drug for such an application should induce anxiolytic and sleep-favouring effects. Due to its pharmacological properties, one would expect opipramol to lead to these effects. In order to test this possibility, 72 female patients were randomly assigned to 50 mg opipramol, 100 mg opipramol, or placebo (n = 24 patients per group) in the evening prior to surgery in a double-blind trial. Effects were recorded in the morning prior to the operation by means of self-rating questionnaires, regarding the patients’ current subjective state and their judgement of the quality of sleep during the night before. The self-rating was done by the Multidimensional Mood Inventory BSKE (EWL), by use of the Multidimensional Somatic Symptom List (MSKL), and by use of the Würzburg Sleep Questionnaire. Further dependent variables were heart rate and blood pressure. Opipramol significantly improved sleep quality. Especially the frequency of awakening at night was reduced. These effects could be observed predominantly after 100 mg opipramol. At this dosage, inner excitement was reduced as well. The autonomic variables remained uninfluenced. There were no adverse events and no hints for interactions with anaesthesiology.
Global Patterns of Child Health: The Role of Nutrition
Authors: Caballero Benjamin
Published: April 2003

Almost two-thirds of the deaths of children around the world are directly or indirectly associated with nutritional deficiencies. Both protein-energy malnutrition and micronutrient deficiencies increase the risk of death from common diseases such as acute gastroenteritis, pneumonia and measles. Iron deficiency anemia is estimated to affect almost 25% of the world’s population (equivalent to 3.5 billion people) resulting in high economic costs by adding to the burden on healthcare services, affecting learning in school and reducing adult productivity. Dietary practices frequently seen in older children and adolescents from industrialized countries, leading to frequent consumption of often nutrient-poor foods, may also put them at risk of micronutrient deficiencies. Marginal nutrient deficiencies in the developed world are increasingly accepted as risk factors for the development of chronic disease such as cardiovascular disease or some cancers.
The Anatomy of a Clinical Trial
Authors: Shepherd J. , Gaw A.
Published: April 2003

Objective: Treatment of hyperlipidemia to reduce the risk of ischemic heart disease was, prior to the statin era, disappointingly limited in its ability to yield the benefits expected from the strong relationship known to exist between serum cholesterol and coronary death. Three primary prevention trials, using clofibrate, cholestyramine and gemfibrozil, had achieved modest reductions in fatal and nonfatal coronary events but none was able to extend life overall or even to reduce cardiovascular mortality; and combined analyses of the three raised disquiet over potential links between cholesterol reduction, cancer and aggressive or violent behaviour. The time was therefore ripe to determine whether statins could help prevent that first and all important myocardial infarction. Methods: The West of Scotland Coronary Prevention Study recruited 6,595 45- to 64-year-old men with no history of prior myocardial infarction and with low-density lipoprotein cholesterol in the range 4–6 mmol/l (155–232 mg/dl). Subjects who had undergone coronary revascularisation or had been hospitalised for angina pectoris in the previous 12 months were excluded, as were those with significant electrocardiographic abnormalities. Participants were randomised to receive pravastatin 40 mg/day or matching placebo and were followed for an average of 4.9 years. Results: Treatment with pravastatin reduced the combined risk of fatal and nonfatal myocardial infarction by 31%. Cardiovascular death overall fell by 32% and the need for coronary revascularisation procedures was reduced by 37%. All of these endpoint benefits were statistically significant. Because there was no increase in non-cardiovascular mortality, the reduction in death from any cause also proved to be statistically significant (p = 0.051 by log rank test and p = 0.037 after adjustment for baseline risk factors). Conclusions: The West of Scotland Coronary Prevention Study is the first to show that cholesterol reduction with pravastatin helps avoid the first myocardial infarction, reduces coronary mortality and extends life. Ongoing exploration of the study database continues to unearth additional surprisingly beneficial effects of the treatment and permits authoritative decision-making on the effective use of lipid-lowering drugs.
Acute Diffuse and Total Alopecia of the Female Scalp
Authors: Sato-Kawamura Maki , Aiba Setsuya , Tagami Hachiro
Published: April 2003

Background: Athough alopecia areata (AA) usually starts with focal lesions of hair loss and then presents several different clinical forms, AA may begin as diffuse hair loss. We examined 9 female patients who presented with acute, diffuse and total hair loss of the scalp and took a similar clinical course with a favorable prognosis. Objective: To categorize such cases as a new subgroup of diffuse alopecia. Methods: We studied 9 patients who showed acute, diffuse and total hair loss of the scalp within 1 month after their first visit to our hospital by comparing their clinical course, laboratory tests and histopathological findings with those of common, patchy AA, alopecia totalis or alopecia universalis. Results: None of the patients had a background of systemic diseases or telogen effluvium. All the patients were female, and 8 of the 9 cases recovered cosmetically acceptable hair growth within 6 months regardless of steroid administration. The histology of he lesions was indistinguishable from that of AA except for a remarkable eosinophilic infiltrate. Conclusions: These cases can be categorized as a new subtype of inflammatory noncicatricial alopecia that is characterized by a marked female predominance, tissue eosinophilia and uniquely short clinical course. We suggest to name it ‘acute diffuse and total alopecia of the female scalp (ADTAFS)’.
The Response of Uninvolved Skin of Patients with Psoriasis to Single and Repeated Applications of Dithranol Cream: An Immunohistochemical Assessment
Authors: Swinkels O.Q.J. , Prins M. , van Vlijmen-Willems I.M.J.J. , Gerritsen M.J.P. , van der Valk P.G.M. , van de Kerkhof P.C.M.
Published: April 2003

Dithranol is one of the most effective topical treatments for patients with psoriasis. The well-known irritation is a serious limitation. In an earlier study we investigated the inflammatory response to single and repeated applications with dithranol 2% cream in skin from healthy volunteers. In the present study, we assessed the clinical and cell-biological response of single and repeated challenges with dithranol 2% cream in uninvolved skin of patients with psoriasis. A striking difference between the two studies is the late phase in the single-challenge group after 8 days, showing a longer-lasting response in the uninvolved skin compared to normal skin with respect to proliferation and inflammation markers. A controlled and synchronised irritation by dithranol might induce anti-inflammatory processes and as such constitute an antipsoriatic principle. It is attractive to speculate that in psoriasis the induction of anti-inflammatory responses is defective. Following repeated applications of dithranol, a more uniform course of proliferation, differentiation and inflammation markers was observed in the uninvolved psoriatic skin as compared to the skin of healthy volunteers. Again a defect in the induction of anti-inflammatory responses might account for this event. In view of these differences between normal skin and psoriatic uninvolved skin, it may be advisable to use the uninvolved skin of patients with psoriasis in further studies on the interference between dithranol irritancy and various anti-inflammatory agents.
A Multicenter Randomized Trial of Ketoconazole 2% and Zinc Pyrithione 1% Shampoos in Severe Dandruff and Seborrheic Dermatitis
Authors: Piérard-Franchimont Claudine , Goffin Véronique , Decroix Jacques , Piérard Gérald E.
Published: April 2003

Ketoconazole (KET) and zinc pyrithione (ZPT) are compounds active against the Malassezia spp. yeasts, which are believed to play a major role in dandruff and seborrheic dermatitis. We compared the efficacy and safety of KET 2% and ZPT 1% in shampoo formulations for the alleviation of severe dandruff and seborrheic dermatitis. This open randomized, parallel-group trial began with a 2-week run-in phase during which subjects applied a neutral nonantidandruff shampoo. It was followed by a 4-week randomized treatment phase and a subsequent 4-week follow-up phase without treatment. Shampooing during the treatment period was carried out twice weekly for the KET group and at least twice weekly for the ZPT group in accordance with the label instructions. A total of 343 subjects were recruited to enter the trial. Of the 331 eligible volunteers, 171 were randomized to KET 2% and 160 to ZPT 1%. Clinical assessments were performed. Beneficial effects were evidenced for both medicated shampoos, but the effect was significantly better for KET 2%, which achieved a 73% improvement in the total dandruff severity score compared with 67% for ZPT 1% at week 4 (p < 0.02). The recurrence rate of the disease was also significantly lower following KET 2% treatment than following ZPT 1% treatment. As a consequence, the overall clearing of the skin condition at the end of treatment and follow-up phase was in favor of the KET 2% formulation (p = 0.004). Side effects were minimal. It is concluded that after a 4-week treatment, KET 2% shampoo was significantly superior to ZPT 1% shampoo in the treatment of subjects with severe dandruff or seborrheic dermatitis of the scalp. It is our assumption that this difference is noticeable for the patient and as a consequence relevant. Both formulations were well tolerated.
Comparison of the Protective Effect of Formoterol and of Salmeterol against Exercise-Induced Bronchospasm when Given Immediately before a Cycloergometric Test
Authors: Ferrari Marcello , Segattini Carlo , Zanon Roberto , Bertaiola Mariano , Balestreri Filippo , Brotto Emanuele , Lo Cascio Vincenzo
Published: April 2003

Background: Salmeterol and formoterol, two long-acting β2-adrenergic agonists, have been shown to be effective against exercise-induced bronchospasm (EIB) several hours after inhalation, but no study has yet compared their protective effect immediately after administration. Objectives: To compare the protective effect of inhaled formoterol and salmeterol against EIB immediately and 4 h after administration. Methods: Double-blind, two-period cross-over study of 11 EIB-positive asthmatic subjects (mean age 21.2 years) administered formoterol 24 µg and salmeterol 50 µg by means of metered-dose inhalers (MDIs) on 2 days separated by an interval of 72 h; the subjects performed two cycloergometric exercise tests immediately and 4 h after dosing. Forced expiratory volume (FEV1) measurements were made before and at the end of exercise, and then after 3, 5, 10, 15, 20, 25 and 30 min. The maximum percentage decrease in FEV1 in the 30 min following exercise was considered. Results: Immediately after drug administration, but not 4 h later, formoterol provided significantly better protection against EIB than salmeterol (p = 0.02). The number of formoterol-treated subjects protected against EIB (i.e. with a <15% decrease in FEV1 after treatment) was 10/11 after the first exercise test and 7/8 after the second; the corresponding figures after salmeterol treatment were 5/11 and 7/8. Conclusions: Our results show that formoterol inhaled via an MDI is effective in preventing EIB as early as within a few minutes of administration, whereas salmeterol does not offer any appreciable protection. On the contrary, the protective effect of the two drugs is clinically equivalent 4 h after administration.
Clinical Equivalence Trial on Budesonide Delivered either by the Novolizer® Multidose Dry Powder Inhaler or the Turbuhaler® in Asthmatic Patients
Authors: Chuchalin A.G. , Kremer H.-J. , Metzenauer P. , O`Keefe E. , Hermann R.
Published: April 2003

Background and Objectives: To investigate the therapeutic equivalence of the two formulations of the glucocorticosteroid budesonide delivered either by the budesonide Novolizer®, i.e. a multidose dry powder inhaler, or by the Pulmicort® Turbuhaler® in asthmatic patients in terms of efficacy, safety and tolerability during a 12-week treatment. Methods: A total of 315 patients were randomised in this open, multicentre study. Inclusion criteria comprised previously diagnosed bronchial asthma of mild to moderate persistent intensity (ranging from 60% to a maximum of 90% predicted FEV1), need for anti-inflammatory therapy, inhalation of β2-sympathomimetics on an as needed to regular basis, reversibility of airway obstruction of >12% after inhalation of 2 actuations of 100 µg salbutamol. Primary variable was FEV1, secondary were other pulmonary function test variables, PC20FEV1 for histamine challenge, morning and evening PEFR, salbutamol usage, asthma symptoms, reactions after inhalation, standard safety variables. Results: The comparison of the FEV1 at study endpoint indicated that the Novolizer® was at least as efficacious as the Turbuhaler® (p < 0.001). All other variables of the pulmonary function tests as well as the asthma symptoms, nocturnal awakenings, PEFR measurements, or salbutamol usage indicated no relevant difference. Only 1 patient (Turbuhaler®) discontinued prematurely due to lack of efficacy. None of the other safety variables (adverse events, laboratory variables, vital signs, etc.) indicated any difference between the groups. Conclusions: The budesonide Novolizer® is therapeutically equivalent to the Pulmicort® Turbuhaler® for the long-term treatment of patients with mild to moderate persistent asthma.
Isolated Growth Hormone Deficiency and the GH-1 Gene: Update 2002
Authors: Binder Gerhard
Published: April 2003

This short review will focus on the mechanisms which are thought to be directly involved in GH expression and particularly on the monogenetic disorders which were shown to cause isolated growth hormone deficiency (IGHD) due to insufficient expression of GH. The overwhelming majority of genetic defects detected in isolated growth hormone deficiency (IGHD) are mutations of the coding region of the GH-1 gene which belongs to a five genes containing gene cluster located on 17q22–24. Depending on the type of the GH-1 gene mutation, the mode of inheritance is recessive or dominant. The promotor region of the GH-1 gene which encompasses the 300 bp of the 5′ flanking region is highly polymorphic, but the functionally important cis-acting elements are conserved. This sequence is sufficient to control GH expression in cultured cells, but not in transgenic mice: the human GH locus control region, an enhancer region of the GH-1 gene located approximately 15–32 kB upstream of the GH-1 coding region was shown to direct pituitary-specific, high-level GH expression in vivo. Promotion of the GH expression needs the coordinate binding of pituitary-specific (i.e., POU1F1) and ubiquitous trans-acting factors to the cis-acting elements. The mutational analysis of trans-acting factors and cis-acting elements of the GH-1 gene has so far not established any defect outside the coding region as the genetic basis of IGHD except for POU1F1 mutations which cause multiple pituitary hormone deficiency including GHD. Several mutations of the GHRH-receptor gene were shown to result in severe IGHD. In the future, the discovery of new defects of the GH expression machinery will add to our understanding of how GH is sufficiently supplied to the organism and will hopefully simplify and improve the diagnostic approach in a subset of children with IGHD.
The Effect of Dentine on Fluorescence Measurements of Enamel Lesions in vitro
Authors: Rousseau C. , Vaidya S. , Creanor S.L. , Hall A.F. , Girkin J.M. , Whitters C.J. , Strang R. , McHugh S.
Published: April 2003

This study aimed to determine the contribution of the underlying dentine and the enamel-dentine junction to measurements of mineral loss from enamel recorded using quantitative light fluorescence (QLF). Sixteen square blocks (5 × 5 mm) were cut from the labial surfaces of extracted bovine incisor teeth. A dental drill was used to remove dentine and the enamel-dentine junction from half of each specimen. All specimens were embedded in epoxy resin and ground to produce a smooth, flat enamel surface. Half of the enamel surface of the block, perpendicular to where the dentine had been removed, was demineralised for 72 h prior to undertaking QLF measurements from the enamel surface to compare fluorescence loss from different areas of the block. QLF readings taken from lesions with no underlying dentine or enamel-dentine junction were very similar to readings from lesions with underlying dentine. A comparison of the two data sets demonstrated a linear relationship with a gradient of 0.95 and a y intercept of –1.24 (r2 = 0.936). From these data, the underlying dentine and enamel-dentine junction did not influence mineral loss in enamel measured using QLF.
Effect of a Mouthrinse Containing Selected Propolis on 3-Day Dental Plaque Accumulation and Polysaccharide Formation
Authors: Koo Hyun , Cury Jaime A. , Rosalen Pedro L. , Ambrosano Gláucia M.B. , Ikegaki Masaharu , Park Yong K.
Published: April 2003

The aim of this study was to evaluate the effect of a mouthrinse containing propolis SNB-RS on 3-day dental plaque accumulation. Six volunteers took part in a double-blind crossover study performed in two phases of 3 days. During each phase the volunteers refrained from all oral hygiene and rinsed with 20% sucrose solution 5 times a day to enhance dental plaque formation and with mouthrinse (placebo or experimental) twice a day. On the 4th day, the plaque index (PI) of the volunteers was scored and the supragingival dental plaque was analyzed for insoluble polysaccharide (IP). The PI (SD) for the experimental group was 0.78 (0.17), significantly less than for the placebo group, 1.41 (0.14). The experimental mouthrinse reduced the IP concentration in dental plaque by 61.7% compared to placebo (p < 0.05). An experimental mouthrinse containing propolis SNB-RS was thus efficient in reducing supragingival plaque formation and IP formation under conditions of high plaque accumulation.
Participation of the 26S Proteasome in the Regulation of Progesterone Receptor Concentrations in the Rat Brain
Authors: Camacho-Arroyo Ignacio , Villamar-Cruz Olga , González-Arenas Aliesha , Guerra-Araiza Christian
Published: April 2003

The aim of this study was to investigate the participation of the 26S proteasome in the regulation of progesterone receptor (PR) concentrations in the rat brain in vivo. Ovariectomized adult female rats were treated with estradiol (10 µg/100 g s.c.), estradiol + progesterone (400 µg/100 g), and vehicle (corn oil/10% ethanol) in the presence or absence of the proteasome inhibitor Z-Ile-Glu (OBu1)-Ala-Leu-H (PSI, 300 µg/100 g). Proteins were extracted from the preoptic area, the hippocampus, and the frontal cortex, and processed for Western blot. Estradiol-induced PR expression in the preoptic area and the hippocampus, whereas progesterone did not modify the effect of estradiol. Neither estradiol nor progesterone modified PR content in the frontal cortex. PSI treatment increased PR content in the preoptic area and the hippocampus. This increase was significant in both regions after 24 h of the treatment with progesterone + PSI in the animals primed with estradiol. In this case, the content of both PR isoforms (PR-A and PR-B) was increased in a similar manner by PSI in the preoptic area (90 and 97%) and in the hippocampus (49 and 50%). PSI did not affect PR content in the frontal cortex. Our results suggest that the 26S proteasome could participate in the turnover of PR in the preoptic area and the hippocampus of the rat in vivo.
Long-Term Effects of Reflux Nephropathy on Blood Pressure and Renal Function in Adults
Authors: Köhler Jan R. , Tencer Jan , Thysell Hans , Forsberg Lillemor , Hellström Mikael
Published: April 2003

Aims: We investigated whether the grade of renal damage assessed by urography in adult patients with vesicoureteral reflux can be used to identify patients at risk of developing hypertension and/or deterioration of renal function. In addition, maternal and fetal outcome of pregnancy was studied. Methods: Vesicoureteral reflux was diagnosed at a median age of 27 years (range 16–60) in 115 patients (98 women). Excluding patients subjected to nephrectomy or heminephrectomy after inclusion (n = 12), 88 patients had renal damage at inclusion urography and a median follow-up time of 16 years. The median follow-up time was 18 years in 15 patients without renal damage. Grading of renal damage was performed and blood pressure, serum creatinine concentration and albuminuria were measured. Hypertension was considered to be present if the systolic blood pressure was ≧140 mm Hg and/or the diastolic blood pressure was ≧90 mm Hg. It was classified as mild (<180 mm Hg systolic and <105 mm Hg diastolic), or moderate to severe (≧180 mm Hg systolic and/or ≧105 mm Hg diastolic). Renal function was classified as stable or deteriorating. Results: There was no significant difference in the frequency of hypertension among those with (52%) or without (33%) renal damage, but moderate to severe hypertension (16 patients) was only seen in patients with renal damage. Median systolic and diastolic blood pressure were higher in patients with than in those without renal damage. Malignant hypertension developed in 4 patients, all had extensive renal damage. Deterioration of renal function occurred in 25 patients, 1 with unilateral and 24 with extensive renal damage (bilateral or in a solitary kidney). This was associated with a high frequency of hypertension (92%) and albuminuria (88%). Sixteen patients developed end-stage renal disease. A total of 242 pregnancies occurred in 89 of the 98 women. Preeclampsia occurred in 16 (18%) women. Conclusion: Hypertension in adult patients with reflux nephropathy occurs with any grade of renal damage, whereas deterioration of renal function was strongly associated with extensive bilateral renal damage or damage in a solitary kidney.
Prevention of Acute Renal Failure in the Critically Ill
Authors: Ronco Claudio , Bellomo Rinaldo
Published: April 2003

Acute renal failure (ARF) is a common and important complication of critical illness and many interventions have been proposed to prevent it. The pathogenesis of acute renal failure during critical illness is poorly understood. Animal models are based on the induction of renal ischemia and do not reflect the dominance of sepsis as a cause of ARF in the clinical arena. Although biological rationale exists for several interventions, none have been shown to be effective in large randomized double-blind multicentre trials. The only interventions with close to level I evidence are confined to the attenuation of radiocontrast nephropathy. The effect on such interventions is, however, of limited clinical relevance to critically ill patients. The maintenance of adequate intravascular filling, cardiac output and renal perfusion pressure and the avoidance of hypoxemia, marked anemia and nephrotoxins remain the only justifiable interventions at this time.
Permeation and Skin Absorption: Reproducibility of Various Industrial Reconstructed Human Skin Models
Authors: Lotte C. , Patouillet C. , Zanini M. , Messager A. , Roguet R.
Published: April 2003

Human reconstructed skin models could be very useful tools to quantify percutaneous permeation and absorption. Before using such models, the reproducibility in the same batch and/or various batches, i.e. the relevance of the results obtained, must be verified. The reproducibility of 3 industrial models – EpiDerm®, Episkin® and SkinEthic® – was tested regarding the permeation and skin absorption of 3 topically applied compounds (with a large range of physicochemical properties): lauric acid, caffeine and mannitol. For all the models, the intrabatch reproducibility was greater than the interbatch reproducibility. According to the batches tested, the larger difference in terms of reproducibility between the 3 models was observed in the case of mannitol, a very poor permeant. In this case, the best reproducibility was observed with EpiDerm and Episkin. Moreover, the rank order of the 3 compounds applied, in terms of permeation and skin absorption, was the same as that expected from ex vivo human skin. Such results revealed human skin models as a promising means to test in vitro permeation and percutaneous absorption of topical products.
40 Years Later: The Health Related Quality of Life of Women Affected by Thalidomide
Authors: Nippert Irmgard , Edler Birgit , Schmidt-Herterich Claudia
Published: April 2003

Objectives: 40 years ago, the sudden increase of births of babies with a range of severe deformities shocked the world. It was caused by the tranquilizer thalidomide. Women who took the drug in the first trimester of pregnancy gave birth to children with a wide but distinctive range of malformations. Thalidomide claimed more than 10,000 victims worldwide. Those who survived are now reaching middle age. Especially women affected by thalidomide may be at special disadvantage because of combined discrimination based on gender and disability. So far, no study has been published that has investigated their quality of life in health and in health care. Methods: A questionnaire using the WHO QOL-BREF instrument for measuring health-related quality of life was distributed among 166 females impaired by thalidomide. A randomized control group matched by age, sex and area of residence filled out a corresponding questionnaire. Results: Women impaired by thalidomide reported significantly lower quality of life in health and health care as compared to their control group. Over a third reported steadily deteriorating conditions, and a statistically significant higher proportion as compared to the controls has already retired from the workforce. They were significantly less frequently married, had fewer children, had less household incomes and were less mobile. However, women impaired by thalidomide are more likely to be satisfied with their safety in daily life, with their physical environment, with their living conditions and with the support they get from their friends. Conclusions: Although there is increasing clinical research on how to use thalidomide as a drug in new therapies, the specific health needs of women impaired by thalidomide are at risk of being neglected.
Metamorphic Changes in GABA Immunoreactivity in the Brainstem of the Bullfrog, Rana catesbeiana
Authors: Simmons Andrea Megela , Chapman Judith A.
Published: April 2003

We examined immunoreactivity for γ-aminobutyric acid (GABA) in auditory and vestibular brainstem nuclei of the bullfrog, Rana catesbeiana, across metamorphosis, a developmental period featuring significant anatomical and functional remodeling of the nervous system. In the early larval period, GABA-immunoreactive cell somata were visible in the vestibular nucleus complex and the torus semicircularis, as well as in the spinal cord, cerebellum and optic tectum. Fiber bundles such as the medial longitudinal fasciculus and the lemnsical pathways also exhibited intense label at these early stages. In contrast, only diffuse neuropil label was visible in the dorsolateral nucleus and the superior olivary nucleus at the same stages. This diffuse immunoreactivity became progressively more reduced over larval development, and stained somata were visible in these medullary nuclei by metamorphic climax stages. In the torus semicircularis, the numbers of labeled somata in both the developing laminar and principal nuclei increased over metamorphic development, and became progressively more organized into distinct layers. The adult pattern of GABA-like immunoreactivity in the auditory brainstem was reached by metamorphic climax stages, coincident with the maturation of the opercularis system, and preceding the final development of the external tympanum and the tympanic conduction pathway. The relatively earlier maturation of vestibular, compared to auditory, areas in the medulla might reflect the behavioral importance of vestibular-mediated motor reactions during tadpole life. The distribution of GABA in auditory brainstem nuclei in both developing and adult frogs is comparable to that observed in mammals and birds.
Reduced Glial Fibrillary Acidic Protein and Glutamine Synthetase Expression in Astrocytes and Bergmann Glial Cells in the Rat Cerebellum Caused by Δ9-Tetrahydrocannabinol Administration during Development
Authors: Suárez I. , Bodega G. , Fernández-Ruiz J.J. , Ramos J.A. , Rubio M. , Fernández B.
Published: April 2003

In this study we analyzed the responses of cerebellar astroglial cells to pre- and perinatal Δ9-tetrahydrocannabinol (THC) exposure in three postnatal ages and both sexes. To determine whether THC during development directly modifies astroglial growth, this study investigated the effects of THC on astroglial morphological changes and on the expression of specific astroglial markers (glial fibrillary acidic protein: GFAP and glutamine synthetase: GS). Our results demonstrated that the administration of THC during development has deleterious effects on astroglial maturation in the cerebellum. These results also indicate that THC might interfere with astroglial differentiation in a way dependent on sex. The effect of cannabinoids on the development of cerebellar astroglial cells (astrocytes and Bergmann glial cells) is to reduce protein synthesis, since both GFAP and GS decreased in astroglial cells, not only during THC exposure but also in adult ages. Our data suggest that pre- and perinatal THC exposure directly interferes with astroglial maturation by disrupting normal cytoskeletal formation, as indicated by the irregular disposition of GFAP and the lower GFAP expression observed at all the ages studied. THC exposure during development may also modulate glutamatergic nervous activity since GS expression is reduced in THC-exposed brains. GS expression increased progressively after THC withdrawal, but GS expression had still not reached control values two months after THC withdrawal. This indicates that glutamate uptake is lower in glial cells exposed to THC, since GS expression is lower than in older controls. Consequently, glutamatergic neurotransmission may be affected by cannabinoid exposure during gestation. Therefore, cannabinoids exert developmental toxicity, at least on astroglial cells, which could contribute to fetal brain growth retardation.
Pharmacokinetics and Absolute Oral Bioavailability of an 800-mg Oral Dose of Telithromycin in Healthy Young and Elderly Volunteers
Authors: Perret C. , Lenfant B. , Weinling E. , Wessels D.H. , Scholtz H.E. , Montay G. , Sultan E.
Published: April 2003

Background: This two-way, randomized, single-dose, crossover study determined the pharmacokinetics and absolute oral bioavailability of telithromycin in young and elderly healthy subjects. Methods: Twelve young (18–40 years) and 12 elderly (>65 years and ≤85 years) subjects received a single 800-mg oral dose of telithromycin or an intravenous infusion of 400 mg (young subjects) or 480 mg (elderly subjects) of telithromycin over 2.5 h in two treatment periods, separated by a 1-week washout period. The plasma concentrations and pharmacokinetic parameters of telithromycin and its major metabolite, RU 76363, were determined. Absolute oral bioavailability was calculated using the area under the plasma concentration-time curve (AUC) from zero hours to infinity. Results: The absolute oral bioavailability of telithromycin was 57% in both young and elderly subjects. The AUC for the metabolite was lower after intravenous infusion of telithromycin, indicating first-pass loss following oral administration. Telithromycin was well tolerated in both groups of subjects. Conclusions: Telithromycin has an absolute oral bioavailability of 57% in young and elderly subjects and is well tolerated.