bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Growth Hormone Replacement Therapy on Bone Markers and Bone Mineral Density in Growth Hormone-Deficient Adults
Authors: Nilsson Anna G.
Published: April 2003

During the 1990s, interest in the effects of growth hormone deficiency (GHD) in adults increased, and several studies were performed to evaluate the effects of growth hormone (GH) substitution therapy in these patients. Because adults with GHD have reduced bone mineral density (BMD) and an increased risk of fractures, the effects of GH replacement therapy on bone metabolism have been evaluated in long-term studies. A universal finding is that the serum and urinary levels of biochemical bone markers increase during GH substitution therapy, and these increases are dose dependent. After years of GH substitution therapy, the levels of biochemical bone markers remain elevated, according to some studies, whereas other studies report that these levels return to baseline. BMD of the spine, hip and forearm increase after 18–24 months of treatment. Bone mineral content (BMC) increases to a greater extent than BMD, because the areal projection of bone also increases. This difference could be caused by increased periosteal bone formation, but a measurement artefact resulting from the use of dual-energy X-ray absorptiometry cannot be excluded as a possible explanation. One study of GH-deficient adults found that, after 33 months of GH treatment, BMD and BMC increased to a greater extent in men with GHD than in women. There is also a gender difference in the increases in serum levels of insulin-like growth factor I and biochemical bone markers during GH treatment. The reason for these findings is unknown, and the role of sex steroids in determining the response to GH therapy remains to be fully elucidated.
Epidemiology of Osteoporotic Fractures
Authors: Dennison Elaine , Cooper Cyrus
Published: April 2003

Osteoporosis constitutes a major public health problem through its association with age-related fractures. These fractures typically occur at the hip, spine and distal forearm. It has been estimated that the lifetime risk of a hip fracture in white women is 17.5%, with a comparable risk in men of 6%. Hip fractures lead to an overall reduction in survival of about 15% (relative or observed/expected survival at 5 years of 0.83), and the majority of excess deaths occur within the first 6 months following the fracture. Such fractures are also associated with considerable morbidity. Although all vertebral deformities do not come to clinical attention, the lifetime risk of clinically diagnosed vertebral fractures is about 15% in white women. Vertebral fractures tend to be associated with back pain and kyphosis, and also with an impairment of survival, though this is likely to be due to clustering of comorbidity. About one-quarter of clinically diagnosed vertebral deformities result in hospitalization.
Metabolic Functions of Liver-Derived (Endocrine) Insulin-Like Growth Factor I
Authors: Isaksson Olle G.P. , Jansson John-Olov , Sjögren Klara , Ohlsson Claes
Published: April 2003

Until now it has been difficult to determine the relative importance of locally produced (autocrine/paracrine) versus systemically derived (endocrine) insulin-like growth factor I (IGF-I) in the intact organism. We recently eliminated IGF-I production in the livers of mice using the Cre/loxP recombination system. These mice displayed a reduction in serum IGF-I levels of more than 80%, but demonstrated normal body growth, suggesting that autocrine/paracrine-acting IGF-I, but not endocrine-acting IGF-I, regulates body growth. Long-term metabolic studies of mice in which IGF-I production had been inactivated in the liver, have shown that the mice have decreased fat mass, but increased serum levels of insulin and cholesterol. Despite the marked increase in plasma insulin following glucose administration, the glucose elimination was not altered in these animals. Thus, the mice showed an adequately compensated insulin resistance. In conclusion, liver-derived or endocrine IGF-I is not required for post-natal statural growth, but seems to be of vital importance for normal carbohydrate and lipid metabolism.
Genistein and Daidzein Stimulate Hyaluronic Acid Production in Transformed Human Keratinocyte Culture and Hairless Mouse Skin
Authors: Miyazaki Kouji , Hanamizu Tomoko , Iizuka Ryoko , Chiba Katsuyoshi
Published: April 2003

We examined the effects of the soy isoflavones genistein (Gen) and daidzein (Dai) on the production of hyaluronic acid (HA) in a transformed human keratinocyte culture and in hairless mouse skin following topical application for 2 weeks. Gen and Dai, but not the glycosides thereof, significantly enhanced the production of HA in vitro and in vivo. Histochemistry using an HA-binding protein revealed that topical Gen and estradiol raised both the density and intensity of HA staining, which was abundant in the murine dermis. It is suggested that Gen and Dai are not released from their respective glycosides in culture or murine skin. Moreover, topical Gen and Dai may prevent and improve the cutaneous alterations caused by the loss of HA in skin.
Impact of Cortisol on Emotions under Stress and Nonstress Conditions: A Pharmacopsychological Approach
Authors: Reuter M.
Published: April 2003

Although the importance of the hypothalamic-pituitary-adrenal axis in emotional stress response is a well-established fact, the causal relationship between glucocorticoids and emotions remains unclear. Therefore, it was tried to elucidate this relationship by an experimental approach in 100 healthy volunteers. The effects of different oral dosages of cortisol (hydrocortisone; 20 and 40 mg) or placebo on emotional states were tested under stress and nonstress conditions in an independent group design. Furthermore, the time of drug application was varied in relation to the onset of the stress/nonstress conditions (1 vs. 2 h prior to exposure). Stress and nonstress conditions were induced by a film depicting violence and neutral scenes, respectively. The results indicate that the application of cortisol ameliorates emotional states irrespective of the time of drug administration and stress exposure. Also the dimensions of activity were increased by cortisol in all experimental conditions, except when applied 1 h before stress onset, indicating an adaptive negative feedback regulation preventing stress-induced overactivation.
Progesterone Inhibits Rejection of Xenogeneic Transplants in the Sheep Uterus
Authors: Majewski A.C. , Hansen P.J.
Published: April 2003

Objectives: One of the proposed roles of progesterone is to prevent maternal immunological destruction of the allogeneic conceptus. Here, it was demonstrated that progesterone allows survival of a xenotransplant placed in the uterine lumen. Methods: Ovariectomized ewes, surgically prepared to have ligatures around each uterine horn, were given daily subcutaneous injections of 50 mg progesterone or vehicle (sesame oil). After 30 days of treatment, mouse hybridoma cells were transplanted to one ligated uterine horn and phosphate-buffered saline was injected into the other horn. The uterus was flushed after an additional 14 days of treatment and hybridoma cells were identified by immunofluorescence. Results: Overall, hybridoma cells were recovered from 4 of 5 progesterone-treated ewes and 1 of 5 vehicle-treated ewes. Immunohistochemical analysis of intercaruncular endometrium using antibodies towards CD8, γδ, and CD45R lymphocyte markers revealed that local presence of hybridoma cells caused a significant increase in CD8+ cells in all tissue compartments. While not significant, the numbers of CD8+ cells in the luminal and glandular epithelium were lower for progesterone-treated ewes. Progesterone tended to increase γδ T cell numbers in the glandular epithelium. Conclusions: Results demonstrate that xenograft rejection in the uterus is associated with an increase in CD8+ cells in the endometrium and that progesterone can inhibit uterine tissue graft rejection responses sufficiently to allow survival or delay rejection of xenograft tissue.
Lipoatrophic Diabetes-Associated Utero-Ovarian Dysfunction: Influence of Cellular Lipid Deposition on Norepinephrine Indices
Authors: Garris David R. , Garris Bryan L.
Published: April 2003

Objective: Elucidation of the intracellular lipoatrophic diabetic state and the concomitant alterations in norepinephrine (NE) parameters characterizing female reproductive failure. Methods: Quantitation of intrinsic NE levels in utero-ovarian and pancreatic tissue samples of C57BL/KsJ (+/?) control and (db/db) diabetic littermate mice was by high performance liquid chromatography (HPLC) and compared with the microspectrofluorometric histofluorescent (HF) localization of cellular and parenchymal NE. Results: Diabetes-associated elevations in HPLC-detectable tissue NE concentrations occurred in all pancreatic and reproductive tract tissue samples as compared to control-matched samples, whereas concurrent HF analysis revealed suppressed perivascular and parenchymal NE depositions in diabetic mice. Conclusions: These data suggest that progressive hypertriglyceridemia/lipidemia may suppress the effectiveness of intrinsic elevations in tissue NE concentrations from effectively counterregulating the deleterious effects of the hyperglycemic, type-2 diabetic condition.
Acute Moderate Alcohol Consumption Affects Cardiovascular Responses in Healthy Males with Different Tolerance Levels
Authors: Schulte Tilman , Warzel Heinz , Westphal Sabine , Müller-Oehring Eva M. , Strasburger Hans , Dierkes Jutta , Sabel Bernhard A.
Published: April 2003

We investigated the effect of acute moderate alcohol consumption or placebo on respiratory sinus arrhythmia (RSA) in 48 healthy participants with different levels of alcohol tolerance but no abuse. In the electrocardiogram recording, auditory stimuli were presented at defined points in the respiratory cycle, which allows a non-invasive measure of CNS control over RSA. After alcohol consumption we found a decrease in RSA with auditory stimulation. Moreover, individuals with low tolerance showed only a slight change in the RSA after alcohol intake compared to baseline, whereas the placebo drink led to a reduced RSA. In subjects with high alcohol tolerance, alcohol consumption led to a reduction of RSA, with no change after placebo. These results suggest a centrally driven influence on RSA that is changed by alcohol ingestion depending upon subjects’ levels of alcohol tolerance.
Neuropsychological Performance and Mood States following Acute Interferon-β-1b Administration in Healthy Males
Authors: Exton Michael S. , Baase Jan , Pithan Volker , Goebel Marion U. , Limmroth Volker , Schedlowski Manfred
Published: April 2003

Interferon-β-1b (IFN-β-1b) has been shown to reduce the relapse rate in patients with relapsing-remitting multiple sclerosis (MS) and disease progression in patients with secondary progressive MS. While acute administration of IFN-β-1b is known to cause flu-like symptoms, chronic medication has been suggested to cause mood alterations and anxiety attacks, and secondary to this neuropsychological deficits that may impair daily life. It is unknown, however, whether the latter symptoms are induced by acute IFN-β-1b administration. Therefore, we examined the impact of a single subcutaneous injection of IFN-β-1b in 8 healthy males. In a crossover design, each subject was injected subcutaneously with either 8 million IU IFN-β-1b or placebo (NaCl) at 8:00 h. Flu-like symptoms (body temperature, heart rate, blood pressure), mood status [‘profile of mood states’, Befindlichkeitsskala (BFS)] and neuropsychological performance (trail marking test, verbal memory test, d2 attention test) and were assessed at baseline, 4, 8 and 24 h after injection. IFN-β-1b increased body temperature, heart rate and fatigue. Nevertheless, acute IFN-β-1b injection did not impair any parameters of neuropsychological performance. Thus, although IFN-β-1b produces physiological symptoms indicative of sickness behavior, these data suggest that IFN-β-1b administration does not have an impact on the cognitive capacity following acute administration.
5-HT2A and 5-HT2C Serotonin Receptors Differentially Modulate Mouse Sexual Arousal and the Hypothalamo-Pituitary-Testicular Response to the Presence of a Female
Authors: Popova Nina K. , Amstislavskaya Tamara G.
Published: April 2003

The role of 5-HT2A and 5-HT2C subtypes of serotonergic receptors in the control of sexual behavior and plasma testosterone regulation was studied in male CBA mice exposed to a sexually receptive female separated by a transparent partition. Introduction of the receptive female induced sexual motivation and arousal in males, as evidenced by a prolonged time spent at the partition, unsuccessful attempts to step across it and a significant increase in plasma testosterone levels. Administration of 5-HT2A receptor antagonists ketanserin (1.0 and 2.0 mg/kg i.p.) or cyproheptadine (1.0 and 2.0 mg/kg i.p.) diminished the behavioral components and prevented the hormonal components of male sexual arousal. Administration of the selective 5-HT2C antagonist RS 102221 (1.0 and 2.0 mg/kg) considerably increased the time spent by males at the partition (p < 0.001) and, at the dose of 2.0 mg/kg, increased plasma testosterone levels (p < 0.01). Administration of ritanserin – a nonselective 5-HT2A/2C antagonist and, to a smaller degree, 5-HT2B antagonist – at doses of 0.1 and 0.5 mg/kg did not significantly influence male behavior and the activating effect of the presence of a female on the hypothalamo-pituitary-testicular system, although it increased resting testosterone levels (p < 0.05). The present findings suggest that 5-HT2A/5-HT2C receptors may be involved in the neural control of male sexual motivation and arousal, presumably by exerting reciprocal facilitative (5-HT2A) or suppressive (5-HT2C) influences.
Identification of a Fourth Opioid Core Sequence in a Prodynorphin cDNA Cloned from the Brain of the Amphibian, Bufo marinus: Deciphering the Evolution of Prodynorphin and Proenkephalin
Authors: Danielson Phillip , Walker David , Alrubaian Jasem , Dores Robert M.
Published: April 2003

In mammals, prodynorphin codes for three C-terminally extended forms of leu-enkephalin. This is not the case for the anuran amphibian, Bufo marinus. A combination of 3′RACE, RT-PCR and 5′RACE protocols was used to clone and characterize a prodynorphin cDNA from the brain of this amphibian that contained two met-enkephalin sequences. One met-enkephalin sequence was located at the N-terminal of Met5-dynorphin A(1–17), and the other met-enkephalin sequence was located in the N-terminal region of B. marinus prodynorphin in a position that aligned with a pentapeptide met-enkephalin site in mammalian proenkephalin. The latter B. marinus met-enkephalin sequence is flanked by sets of paired basic proteolytic cleavage sites. In addition to the extra met-enkephalin sequence and the Met5-dynorphin A(1–17) sequence, the B. marinus prodynorphin contained two C-terminally extended forms of leu-enkephalin [α-neo-endorphin and dynorphin B(1–13)]. In the toad precursor the α-neo-endorphin sequence is identical to human α-neo-endorphin. The B. marinus dynorphin B(1–13) sequence differs from human dynorphin B(1–13) by one amino acid (Thr12 vs. Val12). Steady-state analysis suggests that dynorphin B(1–13) and possibly α-neo-endorphin may be cleaved to yield leu-enkephalin as an end-product in the amphibian brain. Finally, the alignment of the extra met-enkephalin sequence in the N-terminal of B. marinus prodynorphin with the corresponding met-enkephalin site in mammalian proenkephalin adds support to the hypothesis that the prodynorphin gene arose as a duplication of the proenkephalin gene.
Atorvastatin Treatment Prevents Alterations in Coronary Smooth Muscle Nuclear Ca2+ Signaling in Diabetic Dyslipidemia
Authors: Wamhoff B.R. , Dixon J.L. , Sturek M.
Published: April 2003

Atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, alters bulk myoplasmic Ca2+ regulation and inhibits phenotypic modulation and proliferation of vascular smooth muscle in culture. Nuclear Ca2+ (Can) signaling is tightly coupled to transcriptional events and cell growth. Therefore, we hypothesized that in vivo treatment with atorvastatin would attenuate alterations in mitogen-induced Can signaling associated with coronary atherosclerosis. Three groups of male Yucatan pigs were treated for 20 weeks: controls, alloxan-induced diabetics fed an atherogenic diet and diabetics fed an atherogenic diet plus atorvastatin (80 mg/day). Right coronary artery single-cell cytosolic Ca2+ (Cac) and Can responses to the mitogen endothelin-1 (5 × 10–8M) were measured by laser confocal microscopy using the calcium indicator Fluo-4. We observed a 39% increase in Cac and a 52% increase in Can responses to endothelin-1 in cells from diabetic dyslipidemic arteries compared to control. These alterations were prevented in animals treated with atorvastatin. We show that during proliferation, the nucleus of a smooth muscle cell becomes rounded and loses the characteristic multilobular shape, clefts and invaginations. Consistent with this, a redistribution of Ca2+ stores from a transnuclear morphology in controls to a more perinuclear morphology occurred in cells from diabetic dyslipidemic arteries and was prevented by atorvastatin. In addition, the peak Can responses to endothelin-1 were inversely correlated (r = 0.712) with the extent of the transnuclear distribution of Ca2+ stores and directly correlated (r = 0.874) with the extent of atherosclerosis, as assessed in vivo by intravascular ultrasound. These findings indicate that chronic treatment with atorvastatin directly decreases mitogen-induced Can mobilization, which we suggest is related to the spatial localization of Can stores.
Auditory Event-Related Potentials during Phonetic and Semantic Processing in Children
Authors: Henkin Yael , Kishon-Rabin Liat , Gadoth Natan , Pratt Hillel
Published: April 2003

This study was designed to follow the time course of different levels of linguistic processing using auditory event-related potentials (AERPs). A hierarchical set of acoustically controlled stimuli was used to elicit AERPs in 20 normal children who performed discrimination tasks involving pure tones, phonetic ‘easy’ and ‘difficult’ stimuli and semantic stimuli. Results show that (1) AERP latencies were similar for phonetic ‘easy’ and ‘difficult’ stimuli, (2) prolonged P2, N2 and P3 latencies characterized semantic processing compared to phonetic processing, (3) a late negativity was elicited during semantic processing only, (4) P3 amplitudes were larger over the left compared to right scalp during linguistic processing (phonetic and semantic) but were similar during nonlinguistic processing (pure tones) and (5) reaction time was found to be longest for semantic processing whereas performance accuracy was found to be an insensitive measure. These results provide insight into brain processes underlying the perception of speech. Furthermore, they support a dual model of speech perception that includes parallel and serial processing.
The Pre-Vesalian Kidney: Gabriele Zerbi, 1445–1505
Authors: Gaspare De Santo Natale , Bisaccia Carmela , De Santo Rosa Maria , Touwaide Alain
Published: April 2003

Gabriel Zerbi was born in Verona in 1445 and died in Dalmatia in 1505. He was professor of philosophy in Padua at the age of 22, and moved to Bologna where he became professor of medicine and philosophy. In Rome at the time of Sixtus V and Innocentius VIII, he was archiater and professor of medicine. He completed his academic career in Padua where he worked from 1494 to 1505 with a salary of 600 florins a month. A man of vast culture, a philosopher, physician and professor of medicine, he wrote many books: (1) Questiones Metaphysicae; (2) Gerentocomia; (3) De Cautelis Medicorum; (4) Liber anatomiae corporis humani et singulorum membrorum illius; (5) De anatomia infantiis et porci ex traditione Cophonis, and (6) Libellus de preservatione corporum a passione calculosa. His contribution to anatomy was superb. Through him the discipline became the basis of modern medicine. The core of this article deals with some passages of Zerbi’s chapters on the anatomy of the kidneys and bladder.
Use of Natural Substances in the Treatment of Renal Stones and Other Urinary Disorders in the Medieval Levant
Authors: Lev Efraim , Dolev Eran
Published: April 2003

Urinary disorders were common in the ancient world, especially in the Mediterranean region. In semi-arid zones and countries with unreliable water sources, renal stones and other urinary problems occur with greater frequency. A lack of water and correspondingly high levels of calcium saturation are among the main reasons for the formation of calcium sediments in the urinary tract, and it is hardly surprising, therefore, that many generations of physicians and healers have been called upon to treat these disorders, or at least alleviate the pain associated with them. Down the ages, many natural substances have been used for this purpose. This article focuses on 62 plants, 9 animal-based remedies, 1 mineral preparation and 4 medicinal substances of different or uncertain origin, traced in a recent survey of relevant historical literature (both medical and non-medical). Many of these materials, used to treat urinary disorders in the Levant between the 8th and the 18th centuries, had already been in use since the classical period, and several are still used today in traditional medicine.
Renal Physiology between Two Wars: The Contributions of Dr. Harvey Lester White
Authors: Purkerson Mabel L. , Klahr Saulo
Published: April 2003

Harvey Lester White (1896–1977) graduated from Washington University (St. Louis) School of Medicine and subsequently spent his entire professional career in the School’s Department of Physiology. White’s interest in the function of the kidney was evident early in his academic career when he pioneered research related to renal physiology. His first papers dealt with studies of renal tubular function (1923). He performed what appear to represent the first micropuncture studies in the kidney of Necturus maculosus (1926) and thus confirmed the observations of Wearn and Richards regarding glomerular filtration. Through these studies, he was the first to show that glucose reabsorption occurs in the proximal tubules of Necturus. It also appears that White et al. were the first to demonstrate that volume expansion increases bicarbonate excretion in dogs (1926). He studied the influence of posture on renal ‘activity’ in man (1926). Intracapsular pressure determinations in Necturus kidney (1928) were done using micropuncture techniques. White and co-workers presented (1933) a comparison of clearances of creatinine and various sugars confirming the work of Jolliffe, Shannon and Smith (1932) who had proposed the clearances of non-metabolizable sugars to be a measure of glomerular filtration. Between 1932 and 1936, in an effort to better understand the process of glomerular filtration, he began a series of studies on streaming potentials, surface conductance, electro-endosmosis and other related topics. In 1937, White began work on yet another aspect of renal physiology – endocrine influences on renal function. He would immerse himself in these investigations throughout the remainder of his scientific career. We hope that this account will reveal at least a small dimension of the man and his contributions to renal physiology.
The Discovery of Nephrouroameba: Was It Real or Not?
Authors: Bellinghieri G. , Santoro D. , Mallamace A. , Ioli A. , LoGiudice L. , Venniro G. , Savica V.
Published: April 2003

In 1938 Procaccini showed scientific interest in a new kind of ameba, and called it ‘nephrouroameba’ from which the disease ‘nephrouroamebiasis’ is derived. He wrote a paper titled ‘La Nefrouroamoebiasi’ thus describing its history, the biopathogenetic evolutionary cycle of the protozoon, its therapeutic, epidemiological, anatomo-biological, diagnostic, cultural, biological and morphological features. Between 1934 and 1939, Procaccini had the opportunity to follow many patients belonging to a group of Italian soldiers serving in the Eastern Italian Army in Ethiopia. At that time he was responsible for the biopathological laboratory. After a short preclinical stage of fatigue, patients suffering from nephrouroamebiasis showed a nephrotic syndrome with gross hematuria. The symptoms ceased within a few days but residual microhematuria, albuminuria and urine casts persisted for many months. After microscopic observation, he reproduced some protozoons and classified them as a kind of ameba. Critical analysis of his report leads to the morphological identification of Trichomonas, thus excluding his classification as nephrouroamebas.
The Farsighted Studies of the Italian Carlo L. Rovida (1844–1877) on the Nature of Urinary Casts
Authors: Fogazzi G.B. , Testanera G.
Published: April 2003

Carlo L. Rovida (1844–1877) was an Italian physician who graduated in Pavia (1866) and worked in Milan (1868) and Turin (1874), where he ran the Institute of Clinical Medicine at the university. Between 1870 and 1876 Rovida published several studies on the nature of urinary casts, which can still be considered valid today. He distinguished two main types of casts, i.e., ‘colorless’ (hyaline) and ‘yellowish’ (waxy). By painstaking microscopic observation of the urine, performed mainly by microchemical techniques, and histological examination of the kidneys, he came to the conclusion that both types of casts were produced by tubular cells. In addition, he found that the colorless casts were composed of a unique protein, which was different from any other protein known at the time, and which he called ‘cilindrina’ (cylindrine). Instead, Rovida found that the yellowish casts contain a different, ill-defined protein, which was also present in the lateral and basal membrane of the tubular cells. Rovida should be remembered today because his views were much ahead of the prevailing theories of the time, which considered the casts as coagulated fibrin (a view sustained mainly in Germany) or as elements derived from either tubular degeneration or tubular production (a view sustained mainly in the United Kingdom and Sweden); his results concerning the site of production of hyaline casts and their unique nature were confirmed 90 years later, in the early 1960s, when it was demonstrated that these casts are made of Tamm-Horsfall glycoprotein, a protein which is produced by the cells of Henle’s loop; and his conclusions about the special nature of waxy casts were also correct. In fact, even though the true composition of these casts is still not yet totally clear, there is now evidence that they contain a substance different from Tamm-Horsfall protein. Rovida is also a paradigm of how the progress of science is strictly dependent on the development of technology. In fact, it was only when appropriate techniques (e.g., electrophoresis, immunoelectrophoresis, and immunofluorescent microscopy) became available that the nature of casts could be defined with certainty.
Deep Sclerectomy with Collagen Implant: Initial Experience
Authors: Jehn Andrea B. , Böhnke Matthias , Mojon Daniel S.
Published: April 2003

Objective: To evaluate complications of deep sclerectomy with collagen implant (DSCI), a recently introduced nonpenetrating glaucoma-filtering surgical technique. Patients and Methods: 30 eyes of 23 patients with open-angle glaucoma were included in this prospective, noncomparative, interventional case series. In all eyes, preoperative intraocular pressure (IOP) was lowered inadequately by topical antiglaucomatous medications. After undergoing DSCI, the patients were followed prospectively. If necessary, the procedure was combined with cataract surgery or mitomycin C application. Results: In 27 (90%) of 30 eyes, DSCI could be performed. In 3 (10%) of 30 eyes, DSCI had to be transformed intraoperatively into a trabeculectomy because of a large trabecular penetration. Microperforations without further consequences occurred in 2 (7%) of 30 eyes. The mean follow-up was 6.6 ± 3.8 months. IOP dropped from 26.0 ± 6.7 to 13.6 ± 4.7 mm Hg (p < 0.05). Medical glaucomatous treatment was reduced from 2.3 ± 3.8 to 0.3 ± 0.6 (p < 0.05). In cases without cataract, visual acuity decreased from 0.7 ± 0.3 to 0.66 ± 0.4 at the last visit (p > 0.1). Postoperative complications included Seidel (1/27, 4%), encapsulated bleb (4/27, 15%), astigmatism (1/27, 4%), iris capture (2/27, 7%), microhyphema (3/27, 11%) and peripheral anterior synechiae (4/27, 15%). Fifteen (56%) of the 27 eyes needed the following postoperative procedures: laser goniopuncture (8/27, 30%), needling of the filtering bleb (4/27, 15%), surgical revision in the operating theater (3/27, 11%). All 3 eyes where trabeculectomy was performed instead of DSCI had a favorable course. Conclusions: During the evaluation period, complications occurred in about half of the cases. None of the complications was severe or irreversible. Target pressure and a reduction in drug treatment could be achieved in all of the patients.
Bioinformatic Methods for Allergenicity Assessment Using a Comprehensive Allergen Database
Authors: Hileman Ronald E. , Silvanovich Andre , Goodman Richard E. , Rice Elena A. , Holleschak Gyula , Astwood James D. , Hefle Susan L.
Published: April 2003

Background: A principal aim of the safety assessment of genetically modified crops is to prevent the introduction of known or clinically cross-reactive allergens. Current bioinformatic tools and a database of allergens and gliadins were tested for the ability to identify potential allergens by analyzing 6 Bacillus thuringiensis insecticidal proteins, 3 common non-allergenic food proteins and 50 randomly selected corn (Zea mays) proteins. Methods: Protein sequences were compared to allergens using the FASTA algorithm and by searching for matches of 6, 7 or 8 contiguous identical amino acids. Results: No significant sequence similarities or matches of 8 contiguous amino acids were found with the B. thuringiensis or food proteins. Surprisingly, 41 of 50 corn proteins matched at least one allergen with 6 contiguous identical amino acids. Only 7 of 50 corn proteins matched an allergen with 8 contiguous identical amino acids. When assessed for overall structural similarity to allergens, these 7 plus 2 additional corn proteins shared ≧35% identity in an overlap of ≧80 amino acids, but only 6 of the 7 were similar across the length of the protein, or shared >50% identity to an allergen. Conclusions: An evaluation of a protein by the FASTA algorithm is the most predictive of a clinically relevant cross-reactive allergen. An additional search for matches of 8 amino acids may provide an added margin of safety when assessing the potential allergenicity of a protein, but a search with a 6-amino-acid window produces many random, irrelevant matches.
Scintigraphic Evaluation of Lacrimal Glands Using a Rabbit Experimental Model
Authors: Hakim S.G. , Geerling G. , Lauer I. , Sieg P.
Published: April 2003

The aim of this study was to establish an experimental model to evaluate functional changes in lacrimal gland parenchyma using gamma scintigraphy. Although the lacrimal glands of the rabbit have frequently been used for ophthalmological research, scintigraphic evaluation of these glands has received far less attention and we could not find any reports concerning this topic in the literature. Ten rabbits were used for the study; in 4 of them, the orbital region was dissected to provide the topographic anatomy of the lacrimal glands. Four rabbits underwent a static scintigraphy after excision of a unilateral lacrimal gland. Changes in the pattern of tracer uptake indicated the exact position of the gland on the scintiscan. One rabbit served as a control, and another one was used to prove the surgical accessibility of the gland. Using a frontal projection of the head the 99mTcO–4 uptake of the rabbit lacrimal glands could be identified and evaluated in the upper lateral region of the scintiscan. In conclusion, the lacrimal glands of the rabbit provide an appropriate experimental model to study quantitative disturbances of lacrimal secretion using scintigraphy and enable the assignment of functional impairment to morphological changes of the lacrimal parenchyma.
Mitomycin C-Induced Cell Death in Mouse Lens Epithelial Cells
Authors: Park Hyun-Kyung , Lee Kwang-Won , Choi Jun-Sub , Joo Choun-Ki
Published: April 2003

The mode of action of mitomycin C (MMC)-induced cell death in lens epithelia was investigated using cell culture system. The cytotoxicity of MMC on α-TN4 mouse lens epithelial cells (LECs) was measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)-based assay. To determine the type of cell death induced by MMC, we stained LECs with acridine orange and ethidium bromide, and performed TUNEL assay and electron microscopic examination. The activation of MMC was also investigated with N-acetly-L-cystein (NAC), a free radical scavenger, and dicumarol, an inhibitor of DT-diaphorase, to analyze one- and two-electron reduction pathways involved in the activation of MMC. MTT assay showed that 400 µg/ml of MMC decreased the cell viability of the control cells to 45%, and the cytotoxicity of MMC on α-TN4 cells was increased in a dose-dependent manner. Based on the results obtained from acridine orange and ethidium bromide staining, the TUNEL assay, and transmission electron microscopic examination, we confirmed that MMC-induced cell death, at 400 µg/ml of MMC, occurs with necrosis as well as apoptotis. The treatment of cells with 2 mM NAC for 1 h or 20 µM dicumarol for 30 min, prior to 5 min of MMC (400 µg/ml) treatment, restored the growth suppression to 76 and 80% of the control level, respectively. In addition, the cotreatment of cells with NAC and dicumarol restored cell viability to 90% of the control level. The cellular death in MMC-treated LECs showed the involvement of oxidative stress in this apoptosis accounting for 22% of the observed cell death at 400 µg/ml of MMC.
Effect of Oral Contraceptives on Lacrimal Fluid Peroxidase Activity in Women
Authors: Liberati V. , de Feo G. , Madia F. , Marcozzi G.
Published: April 2003

Lacrimal fluid peroxidase has been supposed to be involved in the protection against oxidative damage to the ocular surface. Our recent findings showed the existence of significant cyclic variations in lacrimal fluid peroxidase activity that were positively correlated with those of 17β-estradiol plasma levels throughout the menstrual cycle of fertile women. In the present study lacrimal fluid peroxidase activity of 8 healthy normocyclic women using low-dose oral contraceptives during the monthly cycle was determined. Data showed that low-dose oral contraceptives caused a decrease in lacrimal fluid peroxidase activity and a lack of its cyclic pattern with respect to the enzyme activity of 8 untreated age-matched women. Moreover, this result suggests that lacrimal fluid peroxidase activity could be regulated by estrogen.
General Practitioners’ Accuracy in Diagnosing Skin Cancers
Authors: Offidani Annamaria , Simonetti Oriana , Bernardini Maria Luisa , Alpagut Ayhan , Cellini Andreina , Bossi Guido
Published: April 2003

Background: The incidence of both melanoma and nonmelanocytic skin cancers has risen dramatically during the past decades, skin cancer becoming an important public health concern. Objective: The purpose of this study was to assess the ability of general practitioners (GPs) in the early diagnosis of skin cancers, their correct differential diagnosis of benign lesions and their accuracy in the choice of the treatment. Methods: A multiple-choice questionnaire regarding 7 cases (with 4 figures) were sent to 625 GPs to evaluate their diagnostic abilities. Conclusions: The results indicate that many GPs are not confident in their ability to recognize the most common skin cancers, and knowledge deficiencies were identified.
Lack of Effect of Chlorhexidine Varnish on Streptococcus mutans Transmission and Caries in Mothers and Children
Authors: Dasanayake A.P. , Wiener H.W. , Li Y. , Vermund S.V. , Caufield P.W.
Published: April 2003

In a randomized clinical trial, we evaluated the effect of a 10% chlorhexidine varnish (Chlorzoin®) on the mother-child transmission of Streptococcus mutans and on subsequent caries experience. Chlorhexidine (n = 38) or a placebo varnish (n = 37) was applied to the dentitions of 75 mothers at a time when their first babies were about 6 months old (approximate time of first tooth emergence). Three more applications at weekly intervals and subsequent applications at 6-month intervals followed the initial application. The mother-child pairs were followed up until the child’s fourth birthday. Maternal salivary S. mutans levels in the treatment group remained significantly lower (p < 0.05) compared to the control group up to 12 months after the initial application. However, this intervention did not significantly alter the S. mutans colonization in children or the caries increment in either the mother or the child.
Ultrastructural Basis for the Efficiency of an Ileal Orthotopic Neobladder 27 Years after Surgery
Authors: Orlandini G. , Guizzardi S. , Ferretti S. , Simonazzi M. , Bucci G. , Gatti R.
Published: April 2003

The morphological and functional basis of the excellent clinical outcome of ileal orthotopic neobladders are largely unknown. Only long-term follow-up studies will provide an adequate answer to this unsettled question. We have studied a patient who underwent this type of surgery over 27 years ago. Besides an important secretive adaptation we have found, at the ultrastructural level, that the monolayered epithelium does not show signs of true metaplasia and that changes had occurred in the intercellular junctions, namely that desmosomes are significantly increased. Although limited to a single case, these features, if confirmed by further observations, suggest a working hypothesis for the understanding of the definitive phenotypic adaptation of the ileal epithelium to the new aggressive environment.
Fungating Scrotal Mass
Authors: Nabi G. , Dogra P.N.
Published: April 2003

We present a case of large fungating scrotal mass in a 18-year-old male. Investigations revealed non-seminomatous germ cell tumor with retroperitoneal nodes. Systemic chemotherapy was followed by excision of the mass. This rare presentation is reported here.
Genomic and Functional Investigations of Mutations of the SLC3A1 Gene in Cystinuria
Authors: Lahme Sven , Bichler Karl-Horst , Eggermann Thomas , Lang Florian
Published: April 2003

Background: Cystinuria is the second most frequent autosomal recessively inherited disorder in Europe, and it is based on a disturbance of the transepithelial transport of cystine and amino acids in the proximal renal tubule as well as in the intestinum. From the point of view of the urologist, patients suffering from cystine stones represent an important population because they develop a great number of recurrences which necessitate frequent stone removal. Methods/Results: Advances in the field of molecular genetics have rendered it possible to correlate genotype and phenotype of these patients. In the candidate gene, the SLC3A1 gene, 25 mutations in patients suffering from cystinuria have been described so far. Investigations in our patients (n = 15) as well as results obtained by other study groups have revealed an average detection rate of approximately 50%. The low rate as well as in-depth physiological analyses of the individual mutations indicate that the SLC3A1 is a subunit of a heteromeric complex. This supposition is supported by the structure of the transporter as well as by biochemical analyses of the urine of cystinuric patients and their relatives. Investigations on other genomic segments and candidate genes localized there are being performed. However, it has already appeared that cystinuria is not based on alterations of one single gene, but that a variety of factors combine in the development of this disease. Conclusions: To be able to offer a molecular genetic diagnosis for patients suffering from cystinuria, the search for mutations of the SLC3A1 gene is being expanded and a screening for other candidate genes set up which are designed to early recognize the risk factors of cystinuria as well as to be able to initiate early therapy.
Isolation of Human Leukocyte Antigen (HLA)-Associated Peptide(s) in the Absence of HLA-Restricted Specific Cytolytic T Lymphocytes
Authors: Torabi-Pour N. , Nouri A.M.E. , Saffie R. , Morrow W.J.W. , Oliver R.T.D.
Published: April 2003

Background/Methods: In this study, immunobead purification, dot-blot, immunocytochemical staining, and SDS-PAGE techniques in combination with high-performance liquid chromatography were used to isolate human leukocyte antigen (HLA) class I antigens and associated peptides from a bladder tumour cell line (Fen) before and after gene transfection. Results: The results showed that: (1) Transfection of the class I negative Fen cell line with normal β-microglobulin (β2-m) gene resulted in the restoration of missing class I antigens. (2) The intact class I antigens could be isolated from lysate of the β2-m gene transfected cells using Sepharose CNBr-W6/32 beads. (3) Dissociation of class I antigens from beads and analysis by the SDS-PAGE showed the presence of both free heavy and light chains of class I antigens. (4) More than 22 class I-associated peptides with a molecular weight of 700–3,000 daltons could be isolated from W6/32-loaded beads but only from lysate of HLA-positive Fen cell line. The data also showed that 1 × 106 of positive Fen cells contained about 200 µg total protein of which about 0.10 µg was class I and about 2 ng was class I-associated peptides. Conclusions: These findings demonstrated that the gene transfection approach could be used to restore missing class I antigens on an otherwise class I negative bladder tumour cell line. The results also showed the feasibility of using above techniques for isolation of HLA-associated peptides. These approaches may provide a realistic possibility for identification of putative tumour-specific peptide(s) from tumour specimens with the long-term aim to use such peptide(s) for immunotherapy in cancer patients.
Is Incidental Appendectomy Necessary during Radical Cystectomy?
Authors: Gupta N.P. , Nabi G. , Hemal A.K. , Dogra P.N. , Seth A. , Aron M.
Published: April 2003

Objective: To find out the incidence of acute appendicitis leading to acute abdominal pain and necessitating appendectomy in the follow-up of patients after radical cystectomy and urinary diversions. Methods: A prospective 160 consecutive radical cystectomy patients with urinary diversion in whom appendectomy was not done between January 1991 and June 2001 were reviewed for the incidence of acute appendicitis. Ages ranged between 26 and 73 years. There were 143 males and 17 females. 120 patients had ileal conduit, 20 sigmoid neobladder, 5 continent urinary diversion, and 15 ureterosigmoidostomy as urinary diversion. Each patients was followed up regularly till death or last follow-up. The follow-up ranged between 4 months and 10 years (mean 6 years). Results: Intestinal obstruction (11%) and acute pyelonephritis (16%) were the most common causes of acute abdominal pain. The remaining causes include sigmoid neobladder perforation (0.6%), parastomal hernia (0.6%), urinary retention due to mucus (1.8%) and renal colic (1.8%). In all patients, diagnosis was easily made and they were managed accordingly. None of the patients had acute appendicitis requiring appendectomy on follow-up. Conclusion: Incidental appendectomy is not required during radical cystectomy as the risk of subsequent appendicitis is extremely low.
Endothelial Accumulation of Hydroxyethyl Starch and Functional Consequences on Leukocyte-Endothelial Interactions
Authors: Nohé B. , Burchard M. , Zanke C. , Eichner M. , Krump-Konvalinkova Vera , Kirkpatrick C.J. , Dieterich H.-J.
Published: April 2003

To date, accumulation of hydroxyethyl starch (HES) has been studied mainly in skin specimens, but there are no detailed reports available regarding starch accumulation in the endothelium. Because endothelial cells play an essential role during shock, we studied the accumulation of HES in human umbilical venous endothelial cells (HUVEC). HUVEC (n = 9) were incubated with a fluorescein-conjugated HES 200/0.5 (FITC-HES) at 0.5–20 mg/ml for 1–72 h. FITC-HES was internalized dose- and time-dependently by pinocytosis into secondary lysosomes. Asymptotic elimination curves showed that 50% of the formerly ingested molecules could not be eliminated. Despite accumulation, starch molecules did not attenuate the expression of E-selectin, ICAM-1 or VCAM-1 on TNF-α-activated HUVEC. However, apart from adhesion molecule expression, perfusion studies showed that HES reduced neutrophil adhesion by direct inhibition of integrin-mediated interactions.
Hypokalemia due to Fanconi Syndrome in a Patient with Obstructive Jaundice
Authors: Liamis George , Bairaktari Eleni , Elisaf Moses
Published: April 2003

There are limited data regarding tubular dysfunction in patients with obstructive jaundice. Here, we present a patient aged 79 years with protracted obstructive jaundice due to choledocholithiasis who developed hypokalemia with inappropriate kaliuria as a part of a non-acidotic generalized proximal tubular dysfunction, which included renal phosphate, uric acid and glucose wasting.
Hypersensitivity to Paraoxybenzoic Acid Esters (Parabens) in a Dialysis Patient
Authors: Sato Kiyoko , Kazama Junichiro James , Wada Yoko , Maruyama Hiroki , Narita Ichiei , Gejyo Fumitake , Sugiyama Kentaro , Satoh Hiroshi
Published: April 2003

A 24-year-old woman undergoing chronic dialysis therapy who had been diagnosed as having ‘heparin allergy’ presented acute allergic reaction after the intracatheter injection of a heparin agent. Further investigation revealed that mild eosinophilia had persisted for more than 3 years before this incidence despite avoiding the use of heparin agents. The leukocyte migration inhibition test (LMIT) showed that heparin agent A which was used for the patient showed positive reaction while heparin agent B which was not used for the patient showed a negative reaction. Paraoxybenzoic acid esters (parabens) are contained in heparin agent A but not in heparin agent B. Parabens showed positive reactions on LMIT. Parabens are the most common preservatives in drugs, foods, and cosmetics and they sometimes induce allergic reactions through percutaneous and possibly ingestive sensitization. However, they cause more severe allergic reactions when used intravenously. We concluded that the allergen in this patient was not heparin but parabens. Hypereosinophilia of unknown origin often occurs in dialysis patients. Such patients may be hypersensitive to parabens.
Urinary Complement Factor H in Renal Disease
Authors: Tamano Mariko , Fuke Yoshinobu , Endo Morito , Ohsawa Isao , Fujita Takayuki , Ohi Hiroyuki
Published: April 2003

Background: Complement factor H (hCFH) plays a key inhibitory role in the control of the alternative complement pathway. We examined whether urinary hCFH (U-hCFH) levels is useful as an indirect indicator of renal damage. Methods: Urine samples were obtained from 104 patients with renal disease. Urine was collected with 10 mM EDTA and U-hCFH levels were measured using the BTA TRAK Assay Kit. Results: In the 62 patients with nephritis, the levels of U-hCFH were elevated (range 15–52,198 U/ml) over the normal range (0–14 U/ml). U-hCFH levels of patients with chronic renal failure, lupus nephritis, membranoproliferative glomerulonephritis, focal glomerulosclerosis were higher than that of IgA nephropathy patients (p < 0.05). In the patients with minimal change disease, showed high levels of U-hCFH during the nephrotic syndrome. U-hCFH was correlated significantly with urinary protein and urinary N-acetyl-β-D-glucosaminidase. Conclusion: We demonstrated that U-hCFH was detected in the urine of nephritis patients.