bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucocorticoid-Induced Osteoporosis
Authors: Compston Juliet
Published: December 2003

Osteoporosis is a common and serious complication of glucocorticoid therapy, resulting in increased risk of fragility fractures. Recent studies indicate that fracture risk is increased even at low doses of glucocorticoids and that this increased risk is seen soon after the commencement of glucocorticoid therapy. Both increased bone resorption and reduced bone formation contribute to bone loss, which affects cortical and cancellous sites. A number of interventions have been shown to prevent glucocorticoid-induced bone loss, although the strongest evidence exists for the bisphosphonates etidronate, alendronate and risedronate. Primary prevention of bone loss should be considered in all high-risk individuals taking oral glucocorticoids for 3 months or more, for example those aged 65 years or over or those with a previous fragility fracture. In other glucocorticoid-treated individuals, the decision to treat should be based on bone densitometry.
Genetic Basis for Resistance to Parathyroid Hormone
Authors: Levine Michael A. , Germain-Lee Emily , Jan de Beur Suzanne
Published: December 2003

Pseudohypoparathyroidism (PHP) is associated with biochemical hypoparathyroidism (i.e. hypocalcemia and hyperphosphatemia) due to parathyroid hormone (PTH) resistance rather than to PTH deficiency. Patients with PHP type 1a have a generalized form of hormone resistance plus a constellation of developmental defects termed Albright hereditary osteodystrophy (AHO). Within PHP type 1a families some individuals will show AHO but have normal hormone responsiveness, a variant phenotype termed pseudo-PHP. By contrast, patients with PHP type 1b manifest only PTH resistance and lack features of AHO. These various forms of PHP are due to defects in the GNAS1 gene that lead to decreased expression or activity of the α-subunit of the stimulatory G protein (Gsα). Tissue-specific genomic imprinting of GNAS1 accounts for the variable phenotypes of patients with GNAS1 defects.
Identification of Novel Genes Involved in Congenital Hypothyroidism Using Serial Analysis of Gene Expression
Authors: Moreno José C.
Published: December 2003

Part of the molecular basis of congenital hypothyroidism (CH) has been elucidated by the identification of molecular defects in pituitary- and thyroid-specific genes in patients with various subtypes of hypothyroidism. So far identified genetic defects only explain a small proportion of cases of hypothyroidism. Thus novel research strategies are required to isolate more tissue-specific genes involved in the pathogenesis of CH at present considered ‘idiopathic’ from a molecular perspective. We applied serial analysis of gene expression to human thyroid tissue and developed a computational substraction method to identify tissue-specific genes. The result has been the identification of three genes preferentially expressed in the thyroid gland. The first one encodes part of the thyroid oxidase (THOX2) system. We linked mutations in the THOX2 gene with idiopathic cases of transient and permanent CH. The second transcript identified, DEHAL1, encodes the protein responsible for the recycling of iodine in the thyroid gland and represents the candidate gene for a specific subtype of CH. The third one encodes NM41, a protein currently under investigation which shows features characteristic of the cystine-knot family of proteins, typically involved in early development.
History and Future of Growth Hormone Research
Authors: Kopchick John J.
Published: December 2003

The understanding of the mechanisms of growth hormone (GH) action has seen great accomplishments over the last two decades. These achievements include the cloning of a variety of GH and GH receptor (GHR) genes and cDNAs; solving of the three-dimensional structure of GH and the GH/GHR complex, and the discovery of GH antagonists. These GH antagonists have resulted in a new class of drugs with important clinical implications. Animal models in which the GH/insulin-like growth factor (IGF)-I axis has been perturbed also have resulted in many novel findings. We have now entered the era of genomics and proteomics. Genes and proteins that are up- or downregulated as a function of GH action (or lack thereof) will add to the repertoire of knowledge that will lead to a better understanding of the molecular basis of GH action.
Insulin-Like Growth Factors and Their Binding Proteins in Children Born Small for Gestational Age: Implication for Growth Hormone Therapy
Authors: Ali Omar , Cohen Pinchas
Published: December 2003

The insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are important regulators of growth and metabolism and are the key mediators of the actions of growth hormone (GH). Children born small for gestational age (SGA) have a host of medical problems including an increased risk of poor growth later in life, a tendency to develop metabolic abnormalities and a high incidence of learning disabilities. IGFs and related molecules may be linked to all of these concerns. Mouse models of IGF-I and IGF-II deficiencies have phenotypes reminiscent of human SGA, including slow growth, insulin resistance, and mental dysfunction. Humans with IGF-I mutations are born SGA and exhibit very poor subsequent growth, metabolic syndrome and mental retardation. Current management of children born SGA who present with growth failure during childhood includes treatment with GH. SGA children usually have growth factor levels within the normal range; however, as a group, they display lower IGFBP-3 levels in relation to their IGF-I levels. GH is effective in improving growth in children born SGA, but higher doses of GH are required to achieve optimal outcome, suggesting a component of GH insensitivity in SGA children. As in other indications for GH, a rational monitoring approach (focusing on maintaining IGF levels in the high normal range) is prudent.
Serum Insulin-Like Growth Factor-I Levels and Potential Risk of Type 2 Diabetes
Authors: Dunger D.B. , Ong K.K.L. , Sandhu M.S.
Published: December 2003

The effects of circulating insulin-like growth factor (IGF)-I on increasing insulin sensitivity are well recognized. IGF-I may have a further important role in maintaining β-cell mass, and lower IGF-I activity could explain links between small size at birth and risk of type 2 diabetes in short, obese adults. In the representative Avon Longitudinal Study of Pregnancy and Childhood birth cohort, whereas insulin sensitivity is related to early postnatal weight gain, insulin secretion is related to IGF-I level and statural growth. Adult studies suggest that lower IGF-I levels at baseline predict increased risk for developing impaired glucose tolerance and type 2 diabetes. A common genetic polymorphism in the IGF1 gene could influence size at birth, postnatal growth and type 2 diabetes risk, but results of studies have been inconsistent. Extrapolation of these data to short children born small for gestational age is complex. Some have evidence of IGF-I and insulin resistance, suggesting inherent defects in IGF-I signalling. These children have poor growth responses to growth hormone (GH) therapy and perhaps the highest type 2 diabetes risk. Where these metabolic abnormalities are less severe, responses to GH therapy are good and diabetes risk may then depend on other genetic factors, indicated by a family history of diabetes or origin from ethnic groups with high diabetes prevalence.
Intrauterine Growth Retardation and Consequences for Endocrine and Cardiovascular Diseases in Adult Life: Does Insulin-Like Growth Factor-I Play a Role?
Authors: Beck Jensen Rikke Bodin , Chellakooty Marla , Vielwerth Signe , Vaag Allan , Larsen Torben , Greisen Gorm , Skakkebaek Niels E. , Scheike Thomas , Juul Anders
Published: December 2003

Low birth weight has been associated with an increased incidence of ischaemic heart disease (IHD) and type 2 diabetes. Endocrine regulation of fetal growth by growth hormone (GH) and insulin-like growth factor (IGF)-I is complex. Placental GH is detectable in maternal serum from the 8th to the 12th gestational week, and rises gradually during pregnancy where it replaces pituitary GH in the maternal circulation. The rise in placental GH may explain the pregnancy-induced rise in maternal serum IGF-I levels. In the fetal compartment, IGF-I levels increase significantly in normally growing fetuses from 18 to 40 weeks of gestation, but IGF-I levels are four to five times lower than those in the maternal circulation. Thus IGF-I levels in fetal as well as in maternal circulation are thought to regulate fetal growth. Circulating levels of IGF-I are thought to be genetically controlled and several IGF-I gene polymorphisms have been described. IGF-I gene polymorphisms are associated with birth weight in some studies but not in all. Likewise, IGF-I gene polymorphisms are associated with serum IGF-I in healthy adults in some studies, although some controversy exists. Serum IGF-I decreases with increasing age in healthy adults, and this decline could hypothetically be responsible for the increased risk of IHD with ageing. A recent nested case-control study found that adults without IHD, but with low circulating IGF-I levels and high IGF binding protein-3 levels, had a significantly increased risk of developing IHD during a 15-year follow-up period. In summary, the GH/IGF-I axis is involved in the regulation of fetal growth. Furthermore, it has been suggested that low IGF-I may increase the risk of IHD in otherwise healthy subjects. Hypothetically, intrauterine programming of the GH/IGF axis may influence postnatal growth, insulin resistance and consequently the risk of cardiovascular disease. Thus IGF-I may serve as a link between fetal growth and adult-onset disease.
Penetration of Antimicrobial Agents into the Prostate
Authors: Charalabopoulos Konstantin , Karachalios George , Baltogiannis Dimitrios , Charalabopoulos Alexander , Giannakopoulos Xenofon , Sofikitis Nikolaos
Published: December 2003

In the present review article, the penetration of antimicrobial agents into prostatic fluid and tissue was examined. Three major factors determining the diffusion and concentration of antimicrobial agents in prostatic fluid and tissue are the lipid solubility, dissociation constant (pKa) and protein binding. The normal pH of human prostatic fluid is 6.5–6.7, and it increases in chronic prostatitis, ranging from 7.0 to 8.3. A greater concentration of antimicrobial agents in the prostatic fluid occurs in the presence of a pH gradient across the membrane separating plasma from prostatic fluid. Of the available antimicrobial agents, β-lactam drugs have a low pKa and poor lipid solubility, and thus penetrate poorly into prostatic fluid, expect for some cephalosporins, which achieve greater than or equal to the inhibitory concentration. Good to excellent penetration into prostatic fluid and tissue has been demonstrated with many antimicrobial agents, including tobramycin, netilmicin, tetracyclines, macrolides, quinolones, sulfonamides and nitrofurantoin.
In vitro Activity of Combination Therapy with Cefepime, Piperacillin-Tazobactam, or Meropenem with Ciprofloxacin against Multidrug-Resistant Pseudomonas aeruginosa Strains
Authors: Erdem Ilknur , Kucukercan Metin , Ceran Nurgul
Published: December 2003

The prevalence of multidrug-resistant Pseudomonas aeruginosa strains has been increasing every year, and treatment with various antimicrobial combinations has been offered alternatively in the clinical practice. The aim of this study was to evaluate the in vitro effects of combinations of meropenem, cefepime, or piperacillin-tazobactam with ciprofloxacin against multidrug-resistant P. aeruginosa strains by the time-kill method. The results show that both the combination of two beta lactams with ciprofloxacin and three beta lactams with ciprofloxacin against 4 of 5 multidrug-resistant P. aeruginosa strains has no effect in vitro. The combination of one beta lactam (meropenem, cefepime, piperacillin-tazobactam) with ciprofloxacin has a synergistic effect against one strain of multidrug-resistant P. aeruginosa that is ciprofloxacin susceptible and resistant to meropenem, cefepime, and piperacillin-tazobactam. None of the combinations had an antagonistic effect against these multidrug-resistant strains.
Bcl-2 Overexpression Does Not Prevent but Retards Adriamycin Toxicity in CC531 Colon Carcinoma Cells
Authors: Hoetelmans Rob W.M. , Vahrmeijer Alexander L. , Mulder Gerard J. , van de Velde Cornelius J.H. , Nagelkerke J. Fred , van Dierendonck Jan Hein
Published: December 2003

Background: The Bcl-2 protein is a critical regulator of susceptibility towards cell death induced by antineoplastic drugs. Reduced growth activity and increased glutathione (GSH) levels protect against adriamycin toxicity. We recently demonstrated statistically significantly reduced growth activity and elevated cellular GSH levels in exponentially growing rat CC531 colon carcinoma cells overexpressing the full-length human Bcl-2 protein (CCbcl2#A3). Methods: To assess the importance of reduced growth activity or increased GSH levels, we determined the mitochondrial function, 24 h after adriamycin treatment, in CCbcl2#A3 cells, parental CC531 cells and cells overexpressing the Bcl-2 protein lacking the N-terminal BH4 domain (CCΔBH4): these latter cells contained elevated cellular GSH levels but were not reduced in growth activity. Results: CCbcl2#A3, but not CCΔBH4, cells were 3-fold less susceptible than parental cells suggestive of a protective role for reduced growth but not for increased GSH levels in bcl-2 transfectants. This was confirmed in several growth-inhibited CC531 transfectants and in slowly proliferating (ca. 100% confluent) cell populations compared to exponentially growing (ca. 50% confluent) cell populations. Reduced growth activity might delay the onset of cell death. Therefore, we tested the effect of adriamycin five days after treatment. In this long-term assay we found no differences between the various cells. Conclusion: Reduction of growth activity, for instance by an overexpression of the Bcl-2 protein, only transiently reduced the susceptibility towards adriamycin treatment.
A Double-Blind, Crossover, Randomized Comparison of Granisetron and Ramosetron for the Prevention of Acute and Delayed Cisplatin-Induced Emesis in Patients with Gastrointestinal Cancer: Is Patient Preference a Better Primary Endpoint?
Authors: Koizumi Wasaburo , Tanabe Satoshi , Nagaba Shizuka , Higuchi Katsuhiko , Nakayama Norisuke , Saigenji Katsunori , Nonaka Miwa , Yago Kazuo
Published: December 2003

Background: Serotonin receptor antagonists are recommended by the American Society of Clinical Oncology for the prevention of acute and delayed chemotherapy-induced emesis. However, the most effective agent in this class of antiemetic drugs for preventing emesis has not been clearly defined. We therefore performed a double-blind, crossover, randomized, controlled trial comparing the efficacy of granisetron and ramosetron, using patient preference as the primary endpoint. Methods: Thirty patients receiving two courses of combined chemotherapy (including ≧60 mg/m2 cisplatin) for gastric or esophageal cancer were randomly assigned to the granisetron-ramosetron group (treatment phase 1: granisetron, 3 mg; treatment phase 2: ramosetron, 0.3 mg) or the ramosetron-granisetron group (treatment phase 1: ramosetron, 0.3 mg; treatment phase 2: granisetron, 3 mg). All patients received methylprednisolone sodium, 250 mg i.v., during each treatment phase. Results: The efficacy of granisetron and ramosetron was similar in terms of the suppression of emesis and appetite status. However, the majority of patients (19/30, 63.3%) expressed a preference for granisetron, as compared with 9 patients (30.0%) who preferred ramosetron; 2 patients (6.7%) had no preference (χ2 test: p = 0.008; Fisher’s exact test: p = 0.015). Conclusions: (1) A significant proportion of patients prefer granisetron over ramosetron for the prevention of chemotherapy-induced emesis. (2) Granisetron and ramosetron possess similar effectiveness for the suppression of emesis. (3) The variable of ‘patient preference’ should be accepted as a primary endpoint of antiemetic drug efficacy.
Viral RNA and p24 Antigen as Markers of HIV Disease and Antiretroviral Treatment Success
Authors: Schüpbach Jörg
Published: December 2003

HIV-1 RNA has become the standard for monitoring antiretroviral therapies. Dogma predicts, however, that a viral protein like p24 should be at least as good a marker of HIV disease activity, provided that it is measured with sufficient sensitivity and accuracy. Simple modifications including use of a more efficient virus lysis buffer, heat-mediated destruction of antibodies interfering with antigen detection, and tyramide signal amplification for increased sensitivity have highly improved the HIV-1 p24 antigen assay. The p24 antigen assay is inferior to RT-PCR in detecting viral particles, but the presence of extraviral p24 antigen in most samples makes largely up for this. p24 antigen testing is similarly sensitive and specific in diagnosing pediatric HIV infection, in predicting CD4+ T cell decline and clinical progression at early and late stage of infection, and suitable for antiretroviral treatment monitoring in both adults and children. Notably, p24 antigen was measurable even in patients with stably suppressed viremia, and its concentrations were correlated negatively with the concentrations of CD4+ T cells and positively with the concentrations of activated CD8+ T cell subsets. p24 antigen is an excellent marker of HIV expression and disease activity and can be used in the same fields of application as HIV RNA is used. The test is validated for subtype B, but requires further studies for non-B subtypes.
Principles of Pseudophakic Photic Phenomena
Authors: Aslam Tariq Mehmood , Dhillon Baljean
Published: December 2003

As ophthalmic science develops, the expectations of surgeons and patients undergoing cataract or refractive surgery also advance. Good Snellen visual acuity is not always an indicator for patient satisfaction, and the surgeon must understand the nature and pathogenesis of problems with other less recognised visual functions. This paper discusses the phenomenon of unwanted light images that may occur after surgery due to optical media imperfections, termed pseudophakic photic phenomena. It covers definitions, assessment, high-risk groups and possible explanations for the occurrence of such phenomena.
One-Year Follow-Up of Selective Laser Trabeculoplasty in Open-Angle Glaucoma
Authors: Cvenkel Barbara
Published: December 2003

Background: Selective laser trabeculoplasty (SLT) targets the pigmented trabecular meshwork (TM) cells without damage to the adjacent non-pigmented tissue. A study was conducted to evaluate the efficacy and safety of SLT in the treatment of uncontrolled open-angle glaucoma. Methods: In a prospective non-randomized study 44 eyes of 31 patients with uncontrolled open-angle glaucoma were treated with a frequency-doubled, Q-switched Nd:YAG laser. A total of approximately 50 spots were placed over 180° of the TM at energy levels ranging from 0.7 to 0.9 mJ. Intraocular pressure (IOP) was measured 1, 2, and 24 h, 1 and 2 weeks and 1, 2, 3, 6, 9, and 12 months after treatment. Results: The average pre-operative IOP was 25.6 (SD 2.6) mm Hg (range 22–34). The mean IOP reduction from baseline at 24 h, 3, 6 and 12 months was 7.1 mm Hg (SD 3.5) or 27.6%; 4.2 mm Hg (SD 3.5) or 16.4%; 4.7 mm Hg (SD 4.2) or 18.6%, and 4.4 mm Hg (SD 3.8) or 17.1%, respectively. The percent of eyes with IOP reduction of 3 mm Hg or more at 3, 6 and 12 months was 66, 78 and 62%. A pressure spike of 8 mm Hg or more was detected in 4 eyes (9.1%). Anterior chamber reaction was seen 1 h after SLT and was mild to moderate in 16 eyes (40.4%) and marked in 3 eyes (6.8%). Conclusions: SLT has shown reasonable efficacy in lowering IOP over 1-year follow-up, but there was a tendency for IOP to increase with a longer follow-up. Long-term follow-up studies with a large sample size are needed to determine whether the IOP lowering effect is sustained over time, and to assess the efficacy of repeated SLT.
Visual Function, Quality of Life and Patient Satisfaction after Ophthalmic Surgery: A Comparative Study
Authors: Mozaffarieh Maneli , Krepler Katharina , Heinzl Harald , Sacu Stefan , Wedrich Andreas
Published: December 2003

Purpose: To compare visual acuity, functional visual performance (VF-14), quality of life (QOL) gain (VF-14 gain) and patient satisfaction in a series of patients undergoing common types of ophthalmic surgery. Method: In a prospective trial, the VF-14 QOL questionnaire was administered to 100 patients who underwent surgery by one surgeon between May 2001 and April 2002. The following surgeries were compared: (1) cataract surgery (non-diabetic patients), (2) cataract surgery (diabetic patients), (3) retinal detachment cryo-buckle procedure, (4) pars plana vitrectomy, (5) silicone oil removal. VF-14 questionnaire responses, visual function and clinical data of all patients were recorded pre-operatively and 1 and 3 months postoperatively. Results: In comparison to vitreoretinal surgery, patients who underwent cataract surgery achieved higher VF-14 scores and required less time to recover from the procedure (1 month). The QOL gain (VF-14 gain) was significantly higher in patients who had undergone retinal detachment surgery and vitrectomy (p < 0.0001). The lowest QOL gain was registered in diabetic patients after cataract surgery. Patients with pre-existing eye disease, including patients with improved visual acuity, were least satisfied with the final outcome of surgery. Conclusions: The highest VF-14 score was achieved by patients with no pre-existing ocular disease, who had undergone cataract surgery. The QOL gain was greater in patients with severer initial ocular conditions. Better patient satisfaction can be achieved in patients with pre-existing eye disease by improving pre-operative patient education.
Clinicopathological Study of the Idiopathic Macular Hole: Comparison of Epiretinal Membrane Peeling and Internal Limiting Membrane Peeling
Authors: Kuo Hsi-Kung , Lin Jui-Wei , Kao Ming-Lun , Liu Chi-Chang
Published: December 2003

The aim of this study was to identify the internal limiting membrane (ILM) and epiretinal membrane (ERM) harvested during macular hole surgery under light microscopy and electron microscopy and to evaluate the difference in specimen loss rate with and without the aid of indocyanine green (ICG) staining. Thirty-two consecutive patients (34 eyes) with stage 2–4 macular holes were included. ERM peeling (macular hole with ERM) or ILM peeling (macular hole without ERM), with or without the use of ICG, was used during macular hole surgery with vitrectomy. There were 26 specimens for pathology; 12 specimens (46%) were lost during processing. ICG staining did not reduce the specimen loss rate. The specimens harvested from intentional ILM peeling displayed a smooth, translucent ILM. The specimens harvested from ERM peeling showed moderate cellular proliferation abutting on the ILM, and all specimens had an ILM. The pathological findings confirmed the clinical observations in all the cases studied. The ILM appeared in all specimens harvested by ERM peeling during macular hole surgery. ICG staining does not alter the specimen loss rate during pathological processing.
Tropoelastin Biosynthesis by Corneal Cells
Authors: Isnard N. , Thévenin D. , Robert L. , Renard G.
Published: December 2003

The vertebrate cornea is an avascular tissue and does not contain elastic fibers. We tested the capacity of corneal epithelial cells and stromal keratocytes to synthesize tropoelastin. Explant cultures and cell cultures were obtained from these two cell types in standard culture conditions. Their elastin-synthetic activity was compared to skin explant cultures and to dermal fibroblast cell cultures. Both corneal cell types synthesized tropoelastin as shown by the incorporation of a radioactive precursor followed by immunoprecipitation of tropoelastin. When serial cultures of keratocytes were tested, tropoelastin biosynthesis strongly increased after the 3rd passage and was at the 9th passage more than the double of that of the first passage. When cocultures were studied with or without cell contact, epithelial cells partially inhibited tropoelastin biosynthesis by keratocytes. This inhibition was somewhat stronger (–36%, p < 0.005) with cell-to-cell contact than keeping separate epithelial cells and keratocytes bathing in the same medium (–18%, p < 0.005). When human skin fibroblasts were substituted for keratocytes with cell-to-cell contact, their tropoelastin biosynthesis was also inhibited by corneal epithelial cells (–42%, p < 0.005), to the same extent as for keratocytes. In Transwell culture, this inhibition was again somewhat lower (–36%, p < 0.005). Some diffusible factor produced by epithelial cells is apparently involved. The epithelial inhibition of tropoelastin biosynthesis by stromal keratocytes might represent one of the mechanisms keeping corneal stroma exempt of elastin fibers.
Role of Retinal Detachment Subretinal Fluid on Extracellular Matrix Metabolism
Authors: González-Avila Georgina , Méndez David , Lozano David , Ramos Carlos , Delgado Javier , Iturria Cecilia
Published: December 2003

Purpose: To examine the in vitro effects of subretinal fluid (SRF) from patients with retinal detachment on extracellular matrix turnover. Methods: Matrix metalloproteinase (MMP) activity was explored by radiolabeled substrate degradation and zymography. Human lung fibroblasts were used to analyze SRF effects on collagen synthesis and cell proliferation. Transforming growth factor-β2 (TGF-β2) concentration was determined in SRF samples by a quantitative sandwich enzyme immunoassay. Results: MMP-2 and MMP-9 gelatinolytic activity was observed in all SRF samples. Collagenase activity was not detected in SRF from patients with holes and recurrent retinal detachment. All SRF samples stimulated fibroblast proliferation and collagen synthesis but SRF samples from recurrent retinal detachment patients with previous retinal tears had the largest effect with the largest TGF-β2 concentration. Conclusions: The gelatinolytic activity found in all SRF samples might be associated with the retinal detachment process. Low collagenase activity with an increase in collagen synthesis could indicate a risk factor to the development of proliferative vitreoretinopathy.
Material Properties of Various Intraocular Lenses in an Experimental Study
Authors: Tehrani Mana , Dick H. Burkhard , Wolters Beate , Pakula Tadeusz , Wolf Evan
Published: December 2003

Introduction: With the recent introduction of small-incision cataract surgery, requirements for intraocular lens (IOL) flexibility, strength and hydrophilicity have rapidly evolved. The IOL surface, however, remains a critical factor influencing uveal biocompatibility. Purpose: To objectively quantify factors of material properties of various IOLs using contact angle measurements, differential scanning calorimetry, dynamic-mechanical measurements and scanning electron microscopy. Material and Methods: In our study, 17 currently available IOLs were investigated using contact angle measurements to assess hydrophilicity and biocompatibility, as well as differential scanning calorimetry for the estimation of glass transition temperature. Mechanical capacity and flexibility were investigated using dynamic-mechanical measurements. Additional analysis of the IOL surface was performed using scanning electron microscopy. Results: The contact angle measurements of the studied IOLs revealed similar values within each group. The silicone IOLs had values between 106 and 119°. The PMMA IOLs were found to have a narrower range of values, between 73.2 and 75.5°. Lenses made of hydrogel had values between 59.2 and 69.1°. The heparin-modified surface showed the lowest contact angle of 56.5°. The glass transition temperature was determined by dynamic differential scanning calorimetry. The resulting values were between 118.8 and 113.5°C for PMMA IOLs, 15.5 and 14.0°C for acrylic IOLs, and –91.7 and –119.6°C for silicone IOLs. The dynamic-mechanical measurements revealed that PMMA lenses manifested characteristics similar to glass, whereas silicone lenses had characteristics similar to rubber. Acrylic lenses were between rubber and glass. Scanning electron microscopy revealed smooth dispersion of fibrin on hydrophobic IOLs and a relative lack of fibrin adhesion on hydrophilic materials. Conclusion: These results demonstrate that material properties of various IOL materials are consistent within classes of IOL materials. This suggests that the intraoperative and postoperative behavior of an IOL is predictable and related to its composition, thus allowing surgeons to choose IOLs more appropriate for different surgical situations and individual patient characteristics.
Intravitreal r-TPA and Gas Injection in Traumatic Submacular Hemorrhage
Authors: Holland Detlef , Wiechens Burkhard
Published: December 2003

Aim: To present the technique and efficiency of intravitreal recombinant tissue plasminogen activator (r-TPA) and gas injection in acute submacular hemorrhage (SMH) due to traumatic choroidal rupture. Patients and Methods: 0.4 ml of sulfur hexafluoride was injected into the vitreous cavity in 2 patients with SMH due to traumatic choroidal rupture. In 1 patient gas injection was combined with 50 µg r-TPA. Both patients were closely followed. Results: Preoperative visual acuity was 20/125 in one eye and 20/100 in the other. At the end of the follow-up, visual acuity had improved to 20/32 in both eyes. Conclusion: r-TPA and gas injection into the vitreous body may be an efficient therapy in patients with submacular hemorrhage due to choroidal rupture.
Treatment of Granular Dystrophy with Soft Contact Lenses
Authors: Roters Sigrid , Severin Maria , Konen Walter , Krieglstein Günter K.
Published: December 2003

Purpose: To prevent recurrence of granular dystrophy by treatment with soft contact lenses. Methods: After penetrating keratoplasty, a soft contact lens was fitted in a 61-year-old woman patient with granular corneal dystrophy. The lens was worn continuously for 53 months. Results: No recurrence was observed. However, the other eye, which was operated on first and not treated with a contact lens, showed severe recurrence of the underlying disease, with granular deposits in the stroma. Conclusions: Fitting of a soft contact lens should be considered in this disease after penetrating keratoplasty.
Structure-Function Relationships in Enzymatically Modified Articular Cartilage
Authors: Rieppo Jarno , Töyräs Juha , Nieminen Miika T. , Kovanen Vuokko , Hyttinen Mika M. , Korhonen Rami K. , Jurvelin Jukka S. , Helminen Heikki J.
Published: December 2003

The present study is aimed at revealing structure-function relationships of bovine patellar articular cartilage. Collagenase, chondroitinase ABC and elastase were used for controlled and selective enzymatic modifications of cartilage structure, composition and functional properties. The effects of the enzymatic degradations were quantitatively evaluated using quantitative polarized light microscopy, digital densitometry of safranin O-stained sections as well as with biochemical and biomechanical techniques. The parameters related to tissue composition and structure were correlated with the indentation stiffness of cartilage. In general, tissue alterations after enzymatic digestions were restricted to the superficial cartilage. All enzymatic degradations induced superficial proteoglycan (PG) depletion. Collagenase also induced detectable superficial collagen damage, though without causing cartilage fibrillation or tissue swelling. Quantitative microscopic techniques were more sensitive than biochemical methods in detecting these changes. The Young’s modulus of cartilage decreased after enzymatic treatments indicating significant softening of the tissue. The PG concentration of the superficial zone proved to be the major determinant of the Young’s modulus (r2 = 0.767, n = 72, p < 0.001). Results of the present study indicate that specific enzymatic degradations of the tissue PGs and collagen can provide reproducible experimental models to clarify the structure-function relationships of cartilage. Effects of these models mimic the changes observed in early osteoarthrosis. Biomechanical testing and quantitative microscopic techniques proved to be powerful tools for detecting the superficial structural and compositional changes while the biochemical measurements on the whole uncalcified cartilage were less sensitive.
Deformation of Chondrocytes in Articular Cartilage under Compressive Load: A Morphological Study
Authors: Kääb M.J. , Richards R.G. , Ito K. , ap Gwynn I. , Nötzli H.P.
Published: December 2003

The main function of articular cartilage is to transmit load. The objective of this study was to describe the deformation of chondrocytes under static loading and its relation to collagen matrix deformation. Whole intact rabbit knee joints were loaded statically with either high or low magnitude and long or short duration. Specimens were cryopreserved while under load and prepared for morphological evaluation by field emission scanning electron microscopy. With this method an immediate preservation of the chondrocyte in its loaded state was possible. Static compression of articular cartilage produced a zone-specific deformation of chondrocyte shape, depending on the magnitude and duration of load. Under high-force and long-duration loading, the chondrocytes showed considerable deformation concomitant with the highly deformed collagen fibres. Chondrocyte deformation occurred mostly in the transitional and upper radial zones and less in the lower layers. There was no significant change of the chondrocyte shape in the tangential zone under high- or low-force short-duration loading. These results show that the chondrocytes undergo significant changes in shape ex vivo and that they are sensitive to differences in the magnitude and duration of loads being applied. Chondrocyte deformation is strongly linked to the deformation of the surrounding cartilage collagen matrix.
Mechanical Conditioning Influences the Metabolic Response of Cell-Seeded Constructs
Authors: Shelton Julia C. , Bader Dan L. , Lee David A.
Published: December 2003

Injuries and degenerative diseases to load-bearing soft tissues are extremely common in hospital clinics and involve all ages of the population. Tissue engineering provides a major focus for developments within this area due to the relative failure of graft and prosthetic-based strategies. On implantation, such systems will be subjected to normal physiological forces. It is important, therefore, to understand the effects of mechanical conditioning of cells within repair systems to predict their response and ultimate success in vivo. In the current study two well-characterised model systems, involving dermal fibroblasts seeded onto silicone membranes and chondrocytes seeded in agarose constructs, have been used to study the effects of mechanical loading on cellular activity. The data presented demonstrate that both the tensile conditioning of fibroblasts in monolayer and the compressive loading of chondrocytes in three-dimensional agarose constructs produced distinct responses. In particular, the nature of the strain field associated with the tensile system is important in determining the ultimate cell response. Equally within the compressive system the influence of dynamic frequency was shown to be important. The other critical factors in determining response to both types of conditioning are associated with the age of the cell and its original location within the tissue.
Distribution and Localization of Vinculin-Talin-Integrin System and Dystrophin-Glycoprotein Complex in Human Skeletal Muscle
Authors: Anastasi G. , Amato A. , Tarone G. , Vita G. , Monici M.C. , Magaudda L. , Brancaccio M. , Sidoti A. , Trimarchi F. , Favaloro A. , Cutroneo G.
Published: December 2003

The vinculin-talin-integrin system and the dystrophin-glycoprotein complex (DGC) are two protein systems with structural and signaling functions, allowing interaction between muscle fibers and extracellular matrix. Although numerous studies have been conducted on these systems, their localization and distribution patterns along the nonjunctional sarcolemma are not clear. On this basis, we carried out an indirect immunofluorescence study on the vastus lateralis muscle of human adults not affected by neuromuscular diseases to better define these patterns. Our results showed that all tested proteins of the two systems have a costameric distribution; all tested proteins of the two systems colocalize with each other (about 90–95% of the cases); only α-sarcoglycan in a few cases (about 6%) does not colocalize with other proteins; in about 9–10% of the cases, dystrophin and β-dystroglycan colocalize partially with other proteins; all tested proteins can be localized in different fibers, both in the region of the sarcolemma over I or A bands. The colocalization between the vinculin-talin-integrin and DGC systems may imply their functional interaction involving the structural aspect, by providing a stronger adhesion between sarcolemma and extracellular matrix in well-defined regions of the muscle fiber. Besides, their colocalization may suggest the existence of a mechanism of mutual modulation of the transmitted signals. This reciprocal control may determine, in different conditions, the prevalence of one system over another with a consequent transmission of different messages to the sarcolemma-associated cytoskeleton.
The Mesencephalic Trigeminal Nucleus of the Duck: Development and Apoptosis
Authors: Petrosino G. , Lalatta Costerbosa G. , Barazzoni A.M. , Grandis A. , Clavenzani P. , Bortolami R.
Published: December 2003

The normal development of the mesencephalic trigeminal nucleus (MesV) of the white Peking duck (Anas platyrhynchos) was studied from the 9th day of incubation until hatching and during adulthood. In the early days of embryonic development, neurons are present in the posterior commissure and in the mesenchymal tissue outside the leptomeninges in addition to those in the tectal commissure (TC) and in the optic tectum. Following the internucleosomal cleavage of DNA, a massive loss of neurons in the MesV starts in the 11-day embryo and continues until the 15th day of incubation. On the 16th day, the nucleus consists of a numerically larger medial division located in the TC and a smaller lateral division within the stratum griseum periventriculare as is found in the adult animal. The programmed cell death occurring in the MesV is discussed herein and correlated with the analogous apoptotic phenomena observed in the trigeminal motor nucleus.
Transcription Factor AP-2β Genotype Associated with Anxiety-Related Personality Traits in Women
Authors: Damberg Mattias , Berggård Cecilia , Mattila-Evenden Marja , Rylander Gunnar , Forslund Kaj , Garpenstrand Håkan , Bergman Hans , Gustavsson J. Petter , Jönsson Erik G.
Published: December 2003

Attempts to link transmitter system genes to certain aspects of personality have been performed. Several monoamine-related gene variants have been investigated. We previously reported an association between a transcription factor activating protein-2β (AP-2β) variant and anxiety-related personality traits as estimated by Karolinska Scales of Personality (KSP). To confirm this reported association, we have, in the present study, analysed an enlarged group of healthy volunteers (n = 370) with regard to AP-2β genotype and personality traits. For estimation of personality traits, individuals completed 5 different personality questionnaires, i.e. Swedish Universities Scales of Personality (SSP), Health-Relevant 5- Factor Personality Inventory (HP5i), Temperament and Character Inventory, the Revised NEO Personality Inventory and KSP. In contrast to men, women having two long AP-2β alleles displayed lower scores for muscular tension (KSP; F = 10.65, p = 0.0013), somatic trait anxiety (SSP; F = 7.18, p = 0.0081), trait irritability (SSP; F = 4.51, p = 0.032), mistrust (SSP; F = 4.01, p = 0.0468) and negative affectivity (HP5i; F = 10.20, p = 0.0017) than women with at least one short allele. The data presented in this study, together with our previously published data, suggest that AP-2β intron 2 genotype is associated with low levels of anxiety-related personality traits in women. Hence, these data further suggest the human AP-2β gene as a novel candidate gene in personality.
Relationship between Power Spectra of the Awake EEG and Psychomotor Activity Patterns Measured by Short-Term Actigraphy
Authors: Winkler Dietmar , Pjrek Edda , Pezawas Lukas , Presslich Otto , Tauscher Johannes , Kasper Siegfried
Published: December 2003

Actigraphy is a quantitative method for the measurement of motor activity. In the present study, actigraphy was used to examine psychomotor correlates of brain activity. Thirty-four psychiatric patients (17 males and 17 females) with different diagnoses participated in this investigation. Directly after EEG recording, motor activity was measured with a wrist actimeter for 15 min in patients in the sitting position. The EEG was quantified by spectrum analysis, and the power spectra as well as other EEG-derived variables were correlated with actigraphic parameters. Occipital and temporoparietal β1 power was statistically significantly higher in patients with higher activity scores and lower in those with a high density of sleep (SB) or wake bouts (WB). A high density of SB or WB was also positively correlated with higher mean α power. Immobile phases measured by actigraphy were positively associated with occipital α and with frontal/frontopolar δ activity, preferentially on the side of the left hemisphere. Our results, while preliminary, suggest that short-term actigraphy may be apt to reflect central nervous system arousal.
Expression of cAMP Response Element-Binding Protein in Major Depression before and after Antidepressant Treatment
Authors: Lai I-Ching , Hong Chen-Jee , Tsai Shih-Jen
Published: December 2003

Antidepressants usually take weeks to exert significant therapeutic effects. This lag phase is suggested to be due to neural plasticity, which may be mediated by the coupling of receptors to their respective intracellular signal transduction pathways. Phosphorylated cAMP response element-binding protein (CREB), a downstream target of the cAMP signaling pathway, has been reported to be a molecular state marker for the response to antidepressant treatment in patients with major depressive disorder (MDD). In order to explore the role of CREB expression in MDD, we used quantitative reverse transcriptase-polymerase chain reaction to quantify CREB messenger RNA of the peripheral lymphocytes obtained from 21 MDD patients, before and after antidepressant treatment, and 21 normal controls. The results revealed no significant difference of CREB expression between untreated MDD patients and normal controls. However, after 8 weeks of antidepressant treatment, CREB expression was significantly decreased in MDD patients (p = 0.025). The CREB change is not associated with the types of antidepressants and therapeutic response.
Association between Catechol-O-Methyltransferase Gene Polymorphisms and Wearing-Off and Dyskinesia in Parkinson’s Disease
Authors: Watanabe M. , Harada S. , Nakamura T. , Ohkoshi N. , Yoshizawa K. , Hayashi A. , Shoji S.
Published: December 2003

Catechol-O-methyltransferase (COMT) is an enzyme that inactivates catecholamines, including levodopa. An amino acid change (Val-108-Met) in the COMT protein has been found to result in a change from high to low enzyme activity. In the present study, we genotyped 121 Japanese patients with Parkinson’s disease (PD) and 100 controls. Comparison of the allele frequencies revealed that homozygosity for the low-activity allele was significantly more common among PD patients than the controls (p = 0.047, odds ratio = 3.23). In addition, homozygosity for the low-activity allele was overrepresented in PD patients that exhibited the ‘wearing-off’ phenomenon (p = 0.045, odds ratio = 3.82) or dyskinesia (p = 0.030, odds ratio = 4.80) compared with controls, although these differences were not significant after Bonferroni’s correction. Our results may help understand the mechanism that cause complications of levodopa therapy in PD patients.
Confirmation of the Neurophysiologically Predicted Therapeutic Effects of Trazodone on Its Target Symptoms Depression, Anxiety and Insomnia by Postmarketing Clinical Studies with a Controlled-Release Formulation in Depressed Outpatients
Authors: Saletu-Zyhlarz Gerda Maria , Anderer Peter , Arnold Oliver , Saletu Bernd
Published: December 2003

Early human pharmaco-EEG and subsequent sleep laboratory studies identified trazodone, a 5-HT2 antagonist and 5-HT reuptake inhibitor (SARI), as an antidepressant with therapeutic effects on its target symptoms depressed mood, anxiety and insomnia. On the occasion of the introduction of a controlled-release (CR) formulation (Trittico® 150 mg retard, marketed in Austria by CSC Pharmaceuticals Handels GmbH, Vienna, Austria) in Austria in July 2000, a multi-center, open, clinical post-marketing study on the therapeutic effects, safety and target symptoms of trazodone CR in depression was carried out at 80 offices of Austrian neuropsychiatrists. 549 outpatients (63% females) of all age groups suffering from five different subtypes of depression were enrolled in the study. After a 2-week fixed dose-titration regimen up to 150 mg and a 4-week adjustment period to the optimum dose, 66% of the patients remained on 150 mg, 20% increased the dose and 11% decreased it. Only 3.7% discontinued treatment. Rating by the neuropsychiatrists based on the Clinical Global Impression showed very much to much improvement in 78.3% of the patients, and no change or a deterioration in only 3.6%. In the Hamilton Depression Scale (HAMD) a statistically significant improvement from a baseline score of 21 to a score of 14 after 2 weeks was found, and a normalization to a score of 8 after 6 weeks. Therapeutic effects were similar in the five groups suffering from different subtypes of depression and in patients with and without comedication. Self-rating by the patients based on the Zung Self-Rating Depression Scale (SDS) and Zung Self-Rating Anxiety Scale (SAS) also showed a significant improvement in the 2nd and 6th week of therapy. Evaluation of the target symptoms of trazodone by ranking the most improved symptoms identified insomnia as the most improvedpsychopathological item in all three scales. While in the observer ratings also suicidal tendencies and weight loss were found much improved, in the self-rated Zung SDS sadness and loss of drive came second and third in the improvement ranking, in the self-rated Zung SAS anxiety and the feeling of falling apart. Tolerability was very good. In the 2nd week only 16.9% and in the 6th week only 7.6% of the patients reported side effects, mostly characterized by tiredness and rarely by nausea and vertigo. The present clinical study is in agreement with previous studies identifying trazodone as a safe and effective antidepressant, specifically regarding its target symptoms insomnia, depression and anxiety. It also confirms our own early predictions based on neurophysiological investigations concerning the mode of action of the drug.