bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Hypergastrinemia in Patients with Hyper- and Hypothyroidism: Impact for Calcitonin?
Authors: Vierhapper H. , Nowotny P. , Bieglmayer Ch. , Gessl A.
Published: April 2003

Objectives: To evaluate the prevalence of hypergastrinemia in patients with hyperthyroidism and hypothyroidism and to determine whether gastrin-induced hypercalcitonemia could explain the high prevalence of thyroid C-cell hyperplasia among patients with hyperthyroidism. Methods: Concentrations of gastrin and of hCT were determined by commercially available radioimmunoassays. Results: Elevated serum concentrations of gastrin were found in 17 of 161 (10.5%) patients with manifest hyperthyroidism (Graves’ disease) and in 4 of 37 (10.8%) and 23 of 255 (9.0%) patients with manifest or subclinical hypothyroidism, respectively. Only 2 cases of hypergastrinemia of 255 subclinically hypothyroid patients (0.8%) could not be linked to thyroid autoimmune disease by either biochemical or sonographic criteria. Four patients with Graves’ disease presented elevated plasma concentrations of calcitonin, but none of these patients also had an elevated serum gastrin. Conclusions: The prevalence of hypergastrinemia in autoimmune thyroid disease is about 10%. The determination of gastrin in subclinical hypothyroidism is not cost-effective in the absence of biochemical and/or sonographic markers of autoimmune thyroid disease. The determination of gastrin is of no use to predict the presence of C-cell hyperplasia commonly seen in patients with Graves’ disease.
Phenotypic Heterogeneity Associated with Identical Mutations in Residue 870 of the Androgen Receptor
Authors: Zenteno Juan Carlos , Chávez Bertha , Vilchis Felipe , Kofman-Alfaro Susana
Published: April 2003

Background/Aims: Mutations in the androgen receptor (AR) gene result in an X-linked recessive form of male pseudohermaphroditism known as the androgen-insensitivity syndrome (AIS). The alterations most frequently observed are missense or nonsense point mutations in exons 4–8 of the AR gene that affect the steroid-binding domain of the receptor in subjects with various degrees of androgen resistance. Despite the increasing number of AR mutations identified, a reliable genotype-phenotype correlation has not been established and individuals with the same molecular defect may exhibit different phenotypes. Here, we studied a patients with an AIS characterized by bilateral gynecomastia, normal male external genitalia, and normal sperm counts. Methods: Exon-specific polymerase chain reaction, single-stranded conformational polymorphism, and sequencing analysis of the subject’s AR gene were performed in addition to hormone-binding assays in skin fibroblasts from the patient. Results: A point mutation at codon 870 of the AR, changing alanine to valine, was detected. Conclusion: As AR missense mutations changing alanine 870 to valine have been previously described in 3 unrelated patients showing severe AIS phenotypes, we conclude that phenotypic heterogeneity associated to identical mutations in the AR gene is probably due to individual functional differences in AR coregulator molecules.
Insulin-Like Growth Factors and Insulin-Like Growth Factor Binding Proteins in Adult Patients with Severe Liver Disease before and after Orthotopic Liver Transplantation
Authors: Weber Matthias M. , Auernhammer Christoph J. , Lee Phillip D.K. , Engelhardt Dieter , Zachoval Reinhart
Published: April 2003

Introduction: The liver is the main source of serum insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) and the concentration of these proteins might reflect liver function. Methods: In a retrospective longitudinal study we examined serum levels of total and free IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and IGFBP-6 in 21 adult patients with end-stage liver disease before and after orthotopic liver transplantation (LTX) by sensitive and specific RIAs. In each patient, the mean value of at least three measurements before and after LTX was calculated. Results: Before LTX, serum levels of total and free IGF-I, IGF-II, IGFBP-3 were low and showed a rapid and significant increase in almost all patients after successful LTX (total IGF-I: 30 ± 7 vs. 256 ± 30 ng/ml, p < 0.001; free IGF-I: 1.3 ± 0.3 vs. 3.5 ± 0.6 ng/ml, p < 0.01; IGF-II: 177 ± 28 vs. 618 ± 30 ng/ml, p < 0.001; IGFBP-3: 1,230 ± 136 vs. 3,665 ± 264 ng/ml, p < 0.001). In contrast, IGFBP-1 was found to be high immediately before LTX, and declined to normal levels after LTX (210 ± 40 vs. 90 ± 15 ng/ml, p < 0.01), while IGFBP-2 did not show any significant changes (1,154 ± 296 vs. 1,303 ± 192 ng/ ml). Positive correlations were found between IGF-I, IGF-II or IGFBP-3, and serum pseudocholinesterase (R = 0.50, 0.72 and 0.61 respectively, p < 0.001). Negative correlations were found between IGF-I, IGF-II or IGFBP-3, and prothrombin time (R = 0.50, 0.59 and 0.51 respectively, p < 0.001). Conclusion: Patients with severe liver disease show decreased levels of total and free IGF-I, IGF-II and IGFBP-3, and increased levels of IGFBP-1. These abnormalities are promptly normalized after successful LTX. Thus, serum levels of IGF-I, IGF-II and IGFBP-3 might be useful parameters for the assessment of liver function.
Familial Combined Pituitary Hormone Deficiency Caused by PROP-1 Gene Mutation
Authors: Crone J. , Pfäffle R. , Stobbe H. , Prayer D. , Gomez I. , Frisch H.
Published: April 2003

Background: Mutations of the prophet of PIT-1 (PROP-1), a paired-like homeodomain transcription factor which is responsible for early embryonic pituitary development, have recently been reported as a cause of combined pituitary hormone deficiency. Methods: We describe the phenotype, long-term auxological data and MRI findings in two families with 4 affected members, all of whom have a mutation of the PROP-1 gene. GH, TSH, PRL, LH and FSH were completely deficient in all patients. Results: ACTH deficiency was not diagnosed until the 3rd or 4th decades of life. Pituitary MRI showed an empty sella in 2 subjects, but unspecific tissue accumulation resembling a pituitary mass lesion in another patient. The affected boy from family II who was continuously treated with all the necessary hormones reached the familial target height. However, the 3 subjects in family I were only treated sporadically (GH treatment lasting from 1 to 3 years). Conclusion: Despite this insufficient therapy, final height was in the lower normal range. Longitudinal growth continued up to the age of 40 years in these subjects.
Prognostic Relevance of Ki-67 Antigen Expression in 329 Cases of Oral Squamous Cell Carcinoma
Authors: Bettendorf O. , Herrmann G.
Published: April 2003

Prognostic relevance of Ki-67 staining in oral squamous cell carcinomas was investigated by immunohistochemical expression in 329 cases of squamous cell carcinoma of the oral cavity due to a formamide pretreatment. The growth fraction (Ki-67 labelling index, LI) was correlated to histopathological grading, lymphocytic reaction, stroma/tumour proportion, pattern of invasion, mitotic rate, degree of keratinisation, tumour size, thickness of tumor, depth of invasion, lymph node involvement and five-year survival rate. Highly significant inverse correlation was found between the Ki-67 LI, the stroma/tumour proportion and the degree of keratinisation whereas no correlation could be established between the Ki-67 LI and all the other histological and clinical paramters. Ki-67 staining alone has no prognostic relevance in oral cancer.
Congenital Adrenal Hyperplasia: Lessons from a Multinational Study
Authors: Frisch H. , Waldhauser F. , Lebl J. , Solyom J. , Hargitai G. , Kovacs J. , Pribilincova Z. , Krzisnik C. , Battelino T.
Published: April 2003

A study group of paediatric endocrinologists was established in Austria, Czech Republic, Hungary, Slovenia and Slovakia in order to investigate various aspects in children with congenital adrenal hyperplasia (CAH). Five hundred and ninety-eight patients with CAH who were diagnosed between 1969 and 1998 were included in order to analyze the following questions. Epidemiological data: There were significantly fewer males (43%) than females (57%), and the percentage of males did not increase during the observation period. Salt wasters (SW) totalled 64.7%, whereas 35.3% had simple virilizing (SV) CAH. Diagnosis was established significantly later in boys than in girls (median of 26 vs. 13 days for SW, p < 0.0001; 1,817 vs. 1,010 days for SV, p < 0.03). Mortality in the general population was significantly lower than in CAH siblings (1.8% vs. 7.0%, p < 0.0001) or in SW children (2.2% vs. 11.3%, p < 0.0001). According to our calculation with the present clinical diagnostic criteria in Central Europe, from 40 expected CAH patients/year, 2–2.5 SW, and one female and four male SV patients will not be diagnosed. Auxological data: Growth data from 341 patients were analyzed retrospectively. Percentiles were constructed in a longitudinal/cross-sectional study and pubertal growth was described in a longitudinal analysis. Growth of SW patients was impaired in early childhood (0–3 years), but followed a normal course until puberty. In contrast, SV children had a normal growth pattern during early childhood, but were above the standard thereafter. The pubertal growth spurt was of normal magnitude in boys and girls, but started too early. Final height was reduced compared with both standard and target heights. There was no correlation between final height and age of starting treatment or the year of birth. Bone age was accelerated in both CAH types, but more so in SV patients. Molecular genetics: Three hundred and fifty-six patients were investigated for 11–14 of the most frequent mutations by direct allele-specific polymerase chain reaction (PCR) and/or PCR followed by sequence-specific oligonucleotide, single strand chain polymorphism and restriction fragment length polymorphism. In the group as a whole, we most frequently found the Intron 2 splice mutation (30.8%) or a deletion/conversion (28.5%). The Intron 2 mutation was most frequent in the Hungarian population, whereas deletions/conversions were found more frequently in Slovenians. The other mutations had a similar distribution to those seen in other populations. Genotype-phenotype correlation confirms previous reports.
Relation between Plasma Homocysteine and Alzheimer’s Disease
Authors: Nilsson Karin , Gustafson Lars , Hultberg Björn
Published: April 2003

Objective: Several studies have shown that plasma total homocysteine (tHcy) concentration is elevated in Alzheimer’s disease (AD). However, it is not clear whether elevated plasma tHcy is a primary cause or a consequence of AD. Method: To elucidate this question, we have analysed plasma homocysteine and its determinants in patients with early (EOAD)- and late-onset AD (LOAD) and compared the findings with those in vascular dementia (VaD) and age- and sex-matched control subjects. Results: One of the main findings in the present study is that in EOAD there is no change in the levels of either plasma tHcy or its determinants compared with an age- and sex-matched control group. The fact that plasma tHcy concentration is normal in EOAD thus indicates that elevated plasma tHcy is not the primary cause of the disease. Another main finding is that patients with mixed dementia (AD and VaD) and patients with VaD showed significantly increased plasma tHcy concentration compared with controls and that plasma tHCy concentration in patients with LOAD and a history of additional cardiovascular disease was elevated compared both with AD patients without such a history and with the controls. Thus, there is an association between elevated plasma tHcy and vascular disease. A third main finding is that patients with AD who were followed up for several years showed a clinical deterioration of dementia and an elevation of plasma tHcy concentration. This finding likewise supports the notion that elevated plasma tHcy is not the primary cause of the disease. Conclusions: The findings suggest that elevated plasma tHcy is not the primary cause of the disease. Furthermore, the findings indicate that elevated plasma tHcy might be a reflection of concomitant vascular disease in AD patients.
Caudate Nucleus Dopamine D2 Receptors in Vascular Dementia
Authors: Allard Per , Englund Elisabet , Marcusson Jan
Published: April 2003

Caudate nucleus dopamine (DA) D2 receptors were studied in patients with vascular dementia (VaD) and in a control group using [3H]raclopride as a radioligand. There was no significant difference in the number of DA D2 receptors in the VaD group as compared with controls. The binding affinity was significantly lower in the VaD group. When the VaD group was subdivided into subjects with or without neuroleptic treatment, there were no differences in the numbers of receptors as compared with controls, and the significant differences in binding affinity remained for both VaD subgroups. The present results are discussed with reference to the previous finding of a reduced density of caudate nucleus DA uptake sites in the same VaD group and to results from studies on DA D2 receptors in Alzheimer’s disease and Parkinson’s disease.
Diagnostic Testing for Nickel Allergic Hypersensitivity: Patch Testing versus Lymphocyte Transformation Test
Authors: Hostýnek Jurij J. , Reagan Katherine E. , Maibach Howard I.
Published: April 2003

This review evaluates the lymphocyte transformation test (LTT) as an in vitro alternative to the traditional patch testing. Patch test results require knowledge, practice and experience for correct biological and clinical interpretation, and in spite of long-term use, the method is fraught with technical and interpretative limitations. Nickel in particular is an allergen eliciting false-positive reactions in patch testing due to the irritancy of test materials; it is sometimes difficult to distinguish an irritant reaction from a true allergic response, and patients may need to be tested more than once. Also false-negative reactions can occur due to varying sensitivity of the patient. It therefore appears reasonable to search for a more objective, in vitro alternative; the LTT appears one procedure which gives relatively reliable results. Still, at this point this method can only be used in association with patch testing, and it has often given results inconsistent with the patch test.
The Specificity of Retinoid-Induced Irritation and Its Role in Clinical Efficacy
Authors: MacGregor Jennifer L. , Maibach Howard I.
Published: April 2003

Many patients undergoing topical retinoid therapy experience erythema, scaling, dryness, burning and pruritus. These symptoms characterize the retinoid-specific irritant contact dermatitis commonly termed ‘retinoid dermatitis’. Other irritants and abrasives cause similar clinical symptoms and histological changes in the skin; however, there are differences in their timing of onset and duration. Unlike that of sodium lauryl sulfate, the transepidermal water loss increase after retinoic acid application is delayed and accompanied by an overall increase in stratum corneum hydration. Tretinoin also increases dermal collagen by stimulating synthesis and inhibiting degradation. This evidence suggests a unique pharmacological activity for retinoids, which is probably a receptor-mediated process. In mice with compromised receptor function, topical tretinoin fails to induce hyperplasia, desquamation and peeling. Many retinoid actions in the skin are probably receptor mediated, and the irritation, at least the scaling and peeling component, is partly related to these pharmacological effects. While there is convincing evidence that tretinoin may repair solar damage without irritation, there is less consistent evidence that less irritating retinoids can be comparably effective in acne treatment. Taken together, we lack a precise quantification and qualification of the difference between the clinical and irritant effects of these molecules.
Menthol: A Review of Its Sensitization Potential
Authors: Ale S. Iris , Hostýnek Jurij J. , Maibach Howard I.
Published: April 2003

Menthol, a cyclic terpene alcohol found in high concentrations in oils of peppermint and cornmint, has been widely used in over-the-counter medications, cosmetics and confectionery for over a century. However, its clinical pharmacology remains incompletely understood and its sensitization potential and irritant properties have not been thoroughly studied. Analysis of the menthol structure in a quantitative structure-activity relationship model does not identify any protein-reactive functions. Considering the extensive use of menthol there have been only few reports of adverse dermatological effects. After performing an extensive review of the reported cases of sensitization to menthol, we concluded that the literature does not adequately document the clinical relevance of the patch test reactions nor the impact of irritant reactions. We propose a comprehensive approach when testing with a nonstandard substance such as menthol.
Study of the Patch Test Reactions to Myocoptes musculinus (Kekuidani) of NC/F Mice (Atopic Model Mice)
Authors: Sugiura Keiji , Sugiura Mariko , Hayakawa Ritsuko , Shamoto Mikihiro , Takahashi Hisahide
Published: April 2003

Background: Atopic dermatitis is considered to be developed by the IgE-mediated immediate allergy and by the delayed hypersensitivity to causative allergens. We have previously reported that IgE-mediated type I allergy to mites contributed to the development of skin eruptions on atopic model mice (NC mice). Objective: This time, we studied the delayed hypersensitivity skin reaction to mites in NC/F mice. Methods: We conducted 48-hour closed patch testing with Myocoptes musculinus (kekuidani) that is a parasite in NC/F mice and BALB/C mice. Results: At both the 48- and 72-hour readings, 7 (87.5%) out of 8 NC/F mice tested showed positive reactions to M. musculinus. All BALB/C mice showed negative reactions to M. musculinus. All animals showed negative reactions to white petrolatum. Conclusion: Our previous data and results of this study give positive proof that both IgE-mediated immediate allergy and cell-mediated delayed hypersensitivity to a mite antigen contribute to the development of skin eruptions on NC/F mice resembling human atopic dermatitis.
Biometrological Assessment of Skin Protectors against Moderate Cold Threat
Authors: Claes Greet , Piérard Gérald E.
Published: April 2003

Background: Cold injuries represent a serious problem in winter sport practice and other outdoor activities. Some protection is expected to be achieved by specific topical preparations aiming at decreasing heat loss by water evaporation from the skin. Objective: To compare the efficacy of 6 topical formulations enriched or not with rubefacients. The role of the vehicle was also assessed. Methods: A total of 30 trained cyclists tested the products on their forearms. The skin temperature and electrometric values were recorded at baseline following applications of the test products and after 30-min bicycle riding in moderately cold and humid outdoor conditions. Results: At baseline, the skin temperature was increased by rubefacients dispersed by a lipogel and O/W emulsion. This parameter decreased at all test sites after cycling, but the values remained higher at the rubefacient-treated sites compared to the control untreated site. The oil and lipogel formulations achieved partial occlusion decreasing the transepidermal water loss. This effect was maintained after exercise without, however, hindering sweating. Conclusion: Among the presently tested formulations, the rubefacient-enriched lipogels appeared to be the most efficient formulations for maintaining skin temperature in the normal range during sport practice in a moderately cold environment.
Malondialdehyde: A Possible Marker of Ageing
Authors: Gil Pedro , Fariñas Fernando , Casado Angela , López-Fernández Encarnación
Published: April 2003

Background: Numerous recent studies have suggested that oxidative damage may be important in the ageing process, and lipid peroxidation is an important biological consequence of oxidative cellular damage. Objective: The aim of this work was to analyze the activities of the two protective enzymes, superoxide dismutase (SOD) and catalase (CAT), and the levels of malondialdehyde (MDA) to examine the relationship between the ageing process and defence antioxidant and lipid peroxidation. Method: SOD activity was measured in red blood cells using the Minami and Yoshikawa method; CAT activity was measured in hemolysates by the Aebi method, and MDA levels were measured in erythrocytes by high-performance liquid chromatography. Results: SOD activity shows statistically significant differences between newborns and the rest of the sample (ANOVA p < 0.001; Student-Newman-Keuls test p < 0.001). CAT activity did not show significant differences between the age groups. We observed statistically significant differences in MDA levels between the different groups (ANOVA p < 0.001; Student-Newman-Keuls test p < 0.05). In the regression analysis and rectilinear/curvilinear adjustment compared to age, SOD and CAT showed coefficients close to zero (SOD linear = 0.16; SOD exponential = 0.15; CAT linear = 0.056; CAT exponential = 0.068), indicating in that way their independence from age. Only MDA obtained a regression coefficient superior to 0.75 (p < 0.05). The best adjustment was reached through an exponential expression, giving the following parametric relation: MDA = 103.117e0.0021.AGE. No statistically significant variation in SOD and CAT activity and MDA levels, related to sex could be demonstrated. Conclusions: Our data show that old age is associated with an increase in systemic oxidative stress.
The Aromatase Cytochrome P-450 and Its Clinical Impact
Authors: Meinhardt Udo , Mullis Primus-E.
Published: April 2003

Cytochrome P-450 aromatase (P450arom), the key enzyme for estrogen biosynthesis, is encoded by a single gene, namely the CYP19 gene, localized on 15q21.2. The human CYP19 gene spans about 123 kb with a coding region of 9 exons (about 30 kb, exon II–exon X). Although there are a number of alternative first exons and nine different transcriptional start sides with individual promoters that permit tissue-specific regulation of expression, the protein expressed in these various tissue sites (placenta, adipose tissue, brain, bone, ovary, etc.) is the same regardless of the promoter used. P450arom catalyzes the conversion of testosterone to estradiol, of androstenedione to estrone, and of 16α-hydroxylated dehydroepiandrosterone to estriol. As not only androgens but also estrogens are of importance, particularly in the male pubertal development, including bone changes which were classically considered mostly androgen dependent, the features of the aromatase deficiency syndrome in affected boys and girls as well as adult males and females are discussed. There is growing awareness that androgens and estrogens have general metabolic roles that reach far beyond reproductive processes. For instance, estrogen has a significant impact on carbohydrate and lipid metabolism, vascular function, and arteriosclerosis. In addition, extragonadal estrogen biosynthesis plays an important but often underestimated physiological and pathophysiological role, for example in breast cancer and endometriosis. Based on that knowledge, progress has been made as far as treatment and follow-up of these disorders are concerned. In addition, there is a focus on the treatment of children suffering from a lack of P450arom activity.
Differentiated Thyroid Carcinoma in Children and Adolescents
Authors: Arici Cumhur , Erdogan Okan , Altunbas Hasan , Boz Adil , Melikoglu Mustafa , Karayalcin Binnur , Karpuzoglu Tuncer
Published: April 2003

Background: Thyroid carcinoma in childhood and adolescence is uncommon and because of the slow progression of disease the standard treatment is controversial. The aim of this study was to perform a retrospective analysis of treatment results for differentiated thyroid carcinoma in this age group treated in our clinic. Material and Methods: From August 1988 to February 2001, 15 patients between the ages of 8 and 21 years (average 16.8) were treated for differentiated thyroid carcinoma at Akdeniz University Medical School Departments of General and Pediatric Surgery. The patients included 10 (67%) females and 5 (33%) males. None of the patients had a previous positive history of head and neck irradiation. All patients, except 2, were euthyroid at the time of diagnosis. Results: Nine of the patients underwent total thyroidectomy and in 6 cases subtotal thyroidectomy was performed. There were multiple lymph node metastases in 4 (27%) patients and (various forms of) cervical lymph node dissections were performed in these patients. In addition, 2 children (13%) showed pulmonary metastasis. The incidence of surgical complications was 20% (1 permanent, 1 transient hypoparathyroidism and 1 permanent laryngeal nerve injury). Histological examinations revealed the following: papillary carcinoma in 9 (60%), follicular carcinoma in 5 (33%) patients, and Hurthle cell carcinoma in 1 (7%) patient. Postoperative radioiodine ablation was also added to treatment in 10 (67%) of the patients and all patients received L-thyroxine in suppressive doses. After a median follow-up period of 57 months (range 5–149), all patients are alive and disease-free. Conclusion: Our observations suggest that although most children and adolescents with differentiated thyroid carcinoma are seen with more extensive disease than adults, a total or subtotal thyroidectomy with an appropriate lymph node dissection followed by ablative radioiodine treatment carries a more favorable prognosis.
Skin Changes and Tumours after Renal Transplantation
Authors: Avermaete Annelies , Altmeyer Peter , Bacharach-Buhles Martina
Published: April 2003

Skin involvement in chronic renal failure is characterised by a multitude of different aspects. Apart from the typical yellow-brown discolouration of the skin, most often patients complain of pruritus and xerosis cutis. A marked actinic elastosis is noticed. Dialysis treatment alters and partly aggravates these pre-existing skin conditions. When chronic renal failure leads to a kidney transplantation, some of the reversible skin pathology, e.g. pruritus, xeroderma, tends to ameliorate, but a high tendency to develop malignancies becomes prominent.
Effect of a Prostacyclin Analogue, Iloprost, on Urinary Aquaporin-2 Excretion in Humans
Authors: Buemi Michele , Di Pasquale Giuseppe , Ruello Antonella , Floccari Fulvio , Aloisi Carmela , Latassa Giuseppe , Corsonello Andrea , Sturiale Alessio , Corica Francesco , Frisina Nicola
Published: April 2003

The regulation of aquaporin-2 (AQP2) water channel excretion in the collecting duct depends mainly on the action of vasopressin (AVP). Recently, however, other regulatory factors have been identified: atrial natriuretic factor, oxytocin and prostaglandins. In healthy volunteers (5 males, 5 females; mean age 23 ± 3 years) we therefore evaluated the effect of a stable analogue of prostacyclin-2 (PGI2), iloprost, on renal function and on the urinary excretion of AQP2 (U-AQP2). After 6 h of iloprost infusion, U-AQP2 increased from 0.8 ± 0.15 to 1.8 ± 0.2 pmol/mg creatinine (p < 0.001), while the urinary flow rate increased from 1.4 ± 0.2 to 1.8 ± 4 (p < 0.01). No significant change was found in the AVP serum concentration, with a basal value of 3.17 ± 0.12 vs. 3.15 ± 0.12 pg/ml after 6 h of prostacyclin infusion. All the values returned to pre-study levels after a recovery period of 6 h. In conclusion, the PGI2 analogue, iloprost, can induce U-AQP2 excretion independent of AVP.
Increased Urinary Excretion of Interleukin-17 in Nephrotic Patients
Authors: Matsumoto Koichi , Kanmatsuse Katsuo
Published: April 2003

Background/Aim: Interleukin (IL)-17 is a newly discovered cytokine that is secreted by activated memory CD4+ T cells and modulated the early stage of immune response. To elucidate the pathophysiology of minimal-change nephrotic syndrome (MCNS), we focused on IL-17, which is one of the key factors in regulating an inflammatory response, and thus determined the daily excretion of IL-17 in urine. Methods: For this purpose, excretion levels of IL-17 were measured in the urine of patients with MCNS during relapse and remission using a highly sensitive sandwich enzyme-linked immunosorbent assay. The data obtained were compared with levels of daily urinary excretion of IL-17 in patients with IgA nephropathy (IgAN). A group of healthy subjects served as control. In both experimental groups urine levels of IL-17 excretion were plotted against their daily urinary protein excretion. Results: We demonstrated increased levels of IL-17 excretion in the urine of patients with MCNS and IgAN as compared to the non-nephrotic and healthy controls. In MCNS the daily urinary IL-17 (uIL-17) excretion was increased and returned to baseline with remission of the nephrotic syndrome (NS). We also demonstrated a positive correlation between urinary protein excretion and daily uIL-17 excretion. Conclusion: Taken together, these data indicate that uIL-17 excretion is increased during the NS, suggesting the possibility that daily uIL-17 excretion may reflect the disease activity of NS.
QT Dispersion in Renal Transplant Recipients
Authors: Koc Mehmet , Toprak Ahmet , Ozener I. Cetin , Bihorac Azra , Tezcan Hakan , Fak Ali Serdar , Akoglu Emel
Published: April 2003

An increased QT dispersion (QTd) is associated with a variety of cardiac diseases and predicts sudden death. Although chronic renal failure patients and patients on hemodialysis are shown to have an increased QTd, evidence of increased QTd in renal transplant patients is scarce. In this study, renal transplant patients were evaluated to find out if they had an increased QTd. Thirty-four renal transplant recipients aged 35 ± 8 years and 34 healthy control subjects aged 34 ± 8 years were included in the study. The mean time after transplantation was 51.8 ± 40.4 (range 5–154) months. The QT interval was measured by 12-lead electrocardiogram, and the QTd was defined as the difference between the maximum and minimum QT interval. Bazett’s formula was used to correct for the heart rate (QTc). Both QTd and QTc dispersion (QTcd) in renal transplant patients were compared with those of control subjects. All patients underwent transthoracic echocardiographic assessment and 24-hour ambulatory blood pressure monitoring. Renal transplant recipients had similar QTd (37 ± 15 vs. 39 ± 17 ms) and QTcd (50 ± 18 vs. 55 ± 20 ms) compared to control subjects. QTd and QTcd were similar in patients with and without left ventricular hypertrophy (QTd 37 ± 14 vs. 36 ± 17 ms and QTcd 50 ± 14 vs. 49 ± 21 ms, respectively). No association was found between QTd and left ventricular mass index or blood pressure measurements. The QTd was not found to be increased in renal transplant recipients as compared with that of healthy controls in this study. Normalization of the QTd after renal transplantation may be through the correction of several factors responsible for increased QTd in uremic patients.
Ultrasonic Tissue Characterization of the Carotid Artery in Chronic Renal Failure Patients
Authors: Rossi Marco , Cupisti Adamasco , Santoro Gino , Morelli Ester , Meola Mario , Barsotti Giuliano
Published: April 2003

The ultrasonic reflectivity of the carotid wall, measured by means of integrated backscatter (IBS) analysis, has recently been evaluated in patients with atherosclerotic diseases and it was considered to be a prognostic marker. We performed B-mode measurement and IBS analysis of the carotid wall in 30 chronic renal failure (CRF) patients (serum creatinine 548 ± 230 µmol/l) on conservative treatment and free of clinical evidence of cardiovascular complications; 14 were normotensives (NT) and 16 were treated hypertensives (TH). Thirty sex- and age-matched healthy subjects served as controls. The IBS carotid index was significantly higher in CRF patients than in controls (31.7 ± 3.5 vs. 28.9 ± 2.3 dB; p < 0.001), and no difference was observed between TH and NT CRF patients. The IBS index was negatively correlated with low-density lipoprotein cholesterol plasma levels (r = –0.46, p < 0.05), and within the group of TH CRF patients the IBS index was also negatively correlated with the body mass index and diastolic blood pressure. The carotid intima-media thickness was similar between uremic patients and controls. This study demonstrates an increment in carotid ultrasonic reflectivity in CRF patients, independent of the presence of overt atherosclerotic damage, and probably related to vascular remodelling linked to CRF. IBS analysis can be a useful tool to detect early changes in arterial wall structure. However, prospective studies should be planned to define its prognostic importance in uremic patients.
High Plasma Adenine Concentration in Chronic Renal Failure and Its Relation to Erythrocyte ATP
Authors: Slominska Ewa M. , Szolkiewicz Marek , Smolenski Ryszard T. , Rutkowski Boleslaw , Swierczynski Julian
Published: April 2003

Background: Concentration of plasma adenine has been found to increase in chronic renal failure (CRF). The aim of the present study was to evaluate whether high plasma adenine concentration contributes to the elevated ATP in erythrocytes of patients with CRF. Methods: Three groups of patients with CRF were studied: (A) 30 patients with different degree of CRF; (B) 11 patients on hemodialysis, and (C) 12 patients after successful renal transplantation. Concentrations of plasma adenine and erythrocyte adenine nucleotides were measured in groups A, B and C. Furthermore, adenine incorporation into erythrocyte adenine nucleotide pool was measured in group A. Results: A positive correlation between plasma adenine and creatinine concentrations was found in CRF as well as between plasma adenine and erythrocyte ATP. Furthermore, positive correlation was evident between the rate of adenine incorporation into erythrocyte adenine nucleotide pool and the severity of CRF. A significant reduction in both plasma adenine and erythrocyte ATP was observed immediately following hemodalysis, but 2 days later, high predialysis plasma adenine and erythrocyte ATP concentrations were restored. Following successful renal transplantation erythrocyte ATP and plasma adenine concentrations reached control values. Conclusion: Our results provide evidence that plasma adenine concentration increases in parallel to the progress of the disease and that it could be responsible for the increase in erythrocyte ATP of patients with CRF.
Renal Transplantation in Patients with Fabry Disease
Authors: Sessa Adalberto , Meroni Mietta , Battini Graziana , Maglio Alessia , Nebuloni Manuela , Tosoni Angela , Panichi Vincenzo , Bertagnolio Barbara
Published: April 2003

Anderson-Fabry disease (AFd) is a rare X-linked disorder characterized by deficiency of α-galactosidase A that leads to systemic accumulation of neutral glycosphingolipids, predominantly globotriaosylceramide (Gb3), in body fluids and visceral tissues, including the kidney. End-stage renal failure is a common manifestation in hemizygous males that often occurs by the third to fourth decade of life. Usually transplanted patients exhibit improvement in clinical symptoms of the disease, probably related to the production of α-galactosidase A from the grafted kidney, but mainly related to the increase in Gb3 clearance by the functioning kidney, and increased survival of red cells due to the correction of the uremic status with an evident decrease in the production of Gb3 depending from hemolysis. Several Fabry patients with successful kidney graft survived for 10–15 years and died for cardiovascular complications related to the metabolic disease. The loss of grafted kidney is due to rejection, thrombosis or sepsis. An important issue considering renal transplantation in AFd is the recurrence of the disease in the kidney graft; however, no evidence regarding this possibility has occurred up to now. We report herein the ultrastructural study of the urinary sediment of a 35-year-old male Fabry patient with a severe clinical form of the disease with progression to ESRF at age 29, and submitted to renal transplantation at 33 years. Ultrastructural findings of the urinary sediment documented several cells, probably tubular epithelial cells, with typical accumulation of myelinic bodies resulting from intracellular storage of neutral glycosphingolipids. This morphological evidence arises the problem of the possible recurrence of AFd in the kidney graft in patients with severe phenotype of the metabolic disease.
Prostate-Specific Antigen Dynamics Predict Risk of Progression in Advanced Prostate Cancer Treated with Bicalutamide plus Castration
Authors: Altwein Jens E. , Schmidt Andreas
Published: April 2003

Objective: The aim of this study was to investigate the prognostic value of prostate-specific antigen (PSA) dynamics in patients treated with combined androgen blockade (CAB). Methods: Patients with locally advanced or metastatic prostate cancer (n = 317) received bicalutamide (50 mg once daily) plus either goserelin acetate or surgical castration for 48 weeks. Cox’s proportional hazard analysis was used to determine whether the decline of PSA following the use of this combination is predictive of a delay in progression. Results: PSA levels at weeks 4 and 12 were statistically significant prognostic markers in predicting disease progression. The PSA rate of change to week 12 was also a statistically significant prognostic marker, although the PSA rate of change at week 4 did not reach statistical significance. These results were statistically less robust than those for PSA levels. Bicalutamide plus castration was well tolerated and effective in advanced prostate cancer. Conclusion: These results suggest that PSA dynamics at weeks 4 and 12 may predict time to progression in advanced prostate cancer treated with CAB.
Influence of Urinary Sialic Acid on Calcium Oxalate Crystal Formation
Authors: Konya E. , Amasaki N. , Umekawa T. , Iguchi M. , Kurita T.
Published: April 2003

Using seed crystal method, whole-urine method, and scanning electron microscopy, the inhibitory effects of sialic acid and osteopontin (OPN) on aggregation/growth of CaOx crystals were investigated. Using the seed crystal method, sialic acid showed an inhibitory effect on CaOx crystal aggregation/growth in a concentration-dependent manner, but almost no effect was observed using the whole-urine method. OPN showed an inhibitory effect on aggregation/growth in both experimental systems. The inhibitory effect of asialo-OPN on aggregation/growth was approximately 20% lower than that of OPN in the experiment using the seed crystal method and approximately 15% lower in the experiment using the whole-urine method. Scanning electron microscopy showed that OPN and sialic acid inhibit the aggregation of CaOx crystals. The above findings show that sialic acid accounts for about 15–20% of the involvement of OPN in CaOx crystallization.
Susceptibility of Streptococcus mutans and Streptococcus sobrinus to Cell Wall Inhibitors and Development of a Novel Selective Medium for S. sobrinus
Authors: Hirasawa M. , Takada K.
Published: April 2003

Representative strains of Streptococcus mutans and Streptococcus sobrinus showed differences in susceptibility to members of the monobactam group of β-lactam antibiotics: S. sobrinus was less sensitive than S. mutans. The minimum inhibitory concentrations of aztreonam (AZT) and carumonam, both of which belong to this group, were 2,000 µg/ml for S. sobrinus and 125 µg/ml for S. mutans. Further addition of fosfomycin, bacitracin and sodium chloride to Mitis Salivarius agar (MS) supplemented with AZT resulted in growth inhibition of S. mutans and oral streptococci other than S. sobrinus, and was therefore used as a selective medium for S. sobrinus (MS-SOB medium). The average growth recovery of laboratory and clinically isolated strains of S. sobrinus on MS-SOB medium was 74.1% compared to that on MS medium. Seventy-eight percent of clinical samples in which S. sobrinus was detected yielded pure growth of S. sobrinus on MS-SOB medium.
Smoking Habit among the Relatives of Patients with Serious Smoking-Related Disorders
Authors: Goksel Tuncay , Ozol Duygu , Bayindir Ulku , Guzelant Asuman
Published: April 2003

Objective: To assess smoking habit and awareness of smoking as a potential cause of disease among relatives of patients with serious smoking-related disorders. Design and Setting: A survey using a face-to-face interview-assisted questionnaire at the Ege University Hospital between October 1998 and March 1999. Subjects: We interviewed 242 relatives of patients with serious smoking-related disorders, of whom 56.6% were female and 43.4% male. The mean age was 41.2 ± 13.2 years (15–75). One relative per patient completed the questionnaire and the chosen relative took care of the patient during his illness and accompanied him during hospital visits. Main Outcome Measures: We assessed the relationship between smoking habit and the perception of smoking as a potential cause of illness by the relatives. Statistical analysis was performed by χ2 test. Results: The prevalence of smoking among relatives was 37.6% [49.5% males (n = 105) and 28.5% females (n = 137), p = 0.0003] and an additional 20.2% were ex-smokers. Of the relatives, 86.4% knew that the diseases were directly related to smoking, and 37.8% of these people were smokers and 21.5% ex-smokers. Only 7.2% reported that they had quit smoking after being influenced by the diseases of the patients. The decision to quit was statistically unrelated to the awareness of smoking as the cause of disease. Of all the relatives, 69.2% had tried to quit at least once, 86.8% considered quitting, and 89.0% considered using professional help for smoking cessation. Conclusion: The findings show that even though this group of smokers is aware of the harmful effects of smoking they cannot successfully quit smoking; however, the majority reconsider quitting and receiving professional help.
Plasma Interleukin-1β, Prolactin, ACTH and Corticosterone Responses to Endotoxin after Damage of the Anterior Hypothalamic Area
Authors: Phelps Christopher P. , Dong Jian Ming , Chen Li T. , Menzies Robert A.
Published: April 2003

This report concerns the use of an animal model described by us [J Submicrosc Cytol Pathol 1995;27:83–89] to investigate neural and endocrine sites for endotoxin (ENDO, E. coli 055:B5, 200 µg/100 g body weight in saline intravenously) effects on immunomodulatory hormone and cytokine release. Plasma interleukin-1β (IL-1β), prolactin (PRL), ACTH and corticosterone responses to ENDO after neurotoxic damage of neurons residing in the anterior hypothalamic area (AHA) were studied in freely behaving male rats. Excitotoxic cell damage in the AHA was produced by bilaterally injecting N-methyl-DL-aspartate (NMA) in artificial cerebrospinal fluid (aCSF) into this brain site. Injections of comparable volumes of aCSF alone served as controls for brain damage associated with the treatment. In both experimental brain manipulations before ENDO challenge the rise in plasma IL-1β concentrations in response to ENDO was reduced by 2-fold at 1 h and 3- to 5-fold at 3 h when compared to controls. Nevertheless, experimental and control brain manipulations did not modulate the expected rise in corticosterone concentrations after ENDO exposure which rose 5-fold above the baseline level in all animals. However, AHA manipulation did reduce plasma ACTH and prolactin concentrations differentially. Introduction of either NMA or the control injection of aCSF alone into AHA reduced plasma ACTH concentrations by 2-fold at 0.5 and 1 h after ENDO. However, there was a greater reduction in the rise of plasma PRL concentrations after ENDO found in NMA-treated groups versus rats receiving control aCSF. These results demonstrate that variable-size hypothalamic damage (a larger lesion produced in AHA by NMA treatment vs. a smaller lesion control after aCSF) can result in a differential blunting of PRL, IL-1β and ACTH release into blood in the face of robust, unmodulated corticosterone increases. In summary, these findings revealed a consistent predominant influence of ENDO on adrenal release of corticosterone as a concomitant to differential IL-1β, ACTH and PRL release after AHA cell loss. In conclusion, these results constitute further evidence for hypothalamic orchestration of a balance between immunotropic and immunosuppressive neuroendocrine-immune events during acute bacterial infection of mammals.
Service-Based Survey of Dystonia in Munich
Authors: Castelon Konkiewitz E. , Trender-Gerhard I. , Kamm C. , Warner T. , Ben-Shlomo Y. , Gasser T. , Conrad B. , Ceballos-Baumann A.O.
Published: April 2003

We performed a service-based epidemiological study of dystonia in Munich, Germany. Due to favourable referral and treatment patterns in the Munich area, we could provide confident data from dystonia patients seeking botulinum toxin treatment. A total of 230 patients were ascertained, of whom 188 had primary dystonia. Point prevalence ratios were estimated to be 10.1 (95% confidence interval 8.4–11.9) per 100,000 for focal and 0.3 (0.0–0.6) for generalised primary dystonia. The most common focal primary dystonias were cervical dystonia with 5.4 (4.2–6.7) and essential blepharospasm with 3.1 (2.1–4.1) per 100,000 followed by laryngeal dystonia (spasmodic dysphonia) with 1.0 (0.4–1.5) per 100,000.
Colour-Coded Mapping Technique in Impression Cytology – Findings in Soft Contact Lens Wearers and Patients with Other External Eye Diseases
Authors: Şengör Tomris , Gürdal Canan , Kirimlioglu Hale , İrkeç Murat , Aydin Sevda
Published: April 2003

This study aimed to demonstrate metaplastic changes in a wide area of conjunctival epithelium using the mapping technique by colouring different stages of metaplastic changes after marking them on a millimetric scale paper under a light microscope. Data of 23 patients were studied: 19 contact lens wearers, 2 cases with dry eyes, 1 with lagophthalmus, 1 with conjunctivitis, and 13 normal subjects as controls. Cellulose acetate paper cut into crescents was applied to nasal and temporal quadrants of the conjunctiva. After evaluating the collected cells under light microscopy, they were marked on a millimetric scale. Almost all the patients had varying degrees of squamous metaplasia; however, significant differences were observed in the distribution and the percentage ratio of these changes. In conclusion the colour-coded mapping method yields valuable information in a broader perspective for determining the distribution and degree of the ocular surface changes caused by different physiological and pathological circumstances.
Correlation between Contrast Sensitivity and Visual Acuity in Retinitis pigmentosa Patients
Authors: Akeo Kiyoshi , Hiida Yoshiki , Saga Masamichi , Inoue Rikako , Oguchi Yoshihisa
Published: April 2003

Purpose: High-contrast figures such as Landolt rings are insufficient to evaluate the function of the foveal cones of retinitis pigmentosa (RP) patients. We investigated the correlation between visual function as determined with Landolt rings and with the Vistech Contrast Sensitivity Function Test (VCTS) at various spatial frequencies, in addition to the Cambridge Low Contrast Grating (CLCG). Methods: The study included 30 retinitis pigmentosa patients (53 eyes). All patients were assessed with Landolt rings, the Vistech method, and the CLCG. We estimated the relative contribution of contrast sensitivity to visual acuity by VCTS at each spatial frequency and by CLCG by simple linear regression analysis. Results: The results of the regression analysis of VCTS at 1.5, 3.0, and 6.0 cycles/degree showed a significant correlation between Landolt rings and VCTS and between CLCG and VCTS that was strongest at 6.0 cycles/degree. There was no significant correlation between Landolt rings and VCTS or between CLCG and VCTS at 12.0 and 18.0 cycles/degree. Patients with a visual acuity of 20/25 and CLCG greater than 100 were divided into two groups according to their contrast sensitivity at 18.0 cycles/degree on VCTS. Conclusions: The VCTS at the highest frequency was useful for evaluating the foveal visual function in RP patients having good visual acuity with the Landolt rings. Thus, contrast sensitivity should be useful in detecting minute impairment or improvement of visual function in RP.