bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetic Study of Two Infusion Schedules of Irinotecan Combined with Cisplatin in Patients with Advanced Gastric Cancer
Authors: Fujitani Kazumasa , Tsujinaka Toshimasa , Hirao Motohiro
Published: April 2003

Objective: Irinotecan (CPT-11) in combination with cisplatin (CDDP) has shown promising antitumor activity for advanced gastric cancer, but the optimal administration schedule of CPT-11 is still controversial. To clarify the pharmacokinetic effects of different CPT-11 administration schedules, we compared two different regimens (continuous infusion of CPT-11 for 24 h and CPT-11 infusion for 90 min) combined with CDDP in patients with advanced gastric cancer. Patients and Methods: Five patients were treated with CPT-11 at a dose of 60 mg/m2 delivered by continuous infusion for 24 h on day 1 and by a 90-min infusion on day 15, together with CDDP daily administered at a dose of 10 mg/m2 on days 1–3 and days 15–17 for 4 weeks. The pharmacokinetics of CPT-11 and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were investigated, as well as the toxicity of therapy. Results: Grade 3 leukopenia was observed in 1 patient after 24-hour infusion and in 1 patient after 90-min infusion of CPT-11. In addition, grade 3 thrombocytopenia was observed in 1 patient after the 90-min infusion. Other adverse reactions were mild, and the planned dose was delivered to all patients. The area under the plasma concentration-time curve of SN-38, the active metabolite from CPT-11, was increased by 24-hour infusion when compared with the 90-min infusion, and there was no increase in toxicity. Conclusion: Protracted infusional CPT-11 combined with CDDP is a practical regimen, and may be appropriate for a future phase II trial.
Metamodulation of the Biogenic Amines: Second-Order Modulation by Steroid Hormones and Amine Cocktails
Authors: Mesce Karen A.
Published: April 2003

An evolutionarily conserved feature of neural systems is that they can be modified by neuromodulators. These modulatory chemical signals include the biogenic amines, octopamine (OA), serotonin (5-HT) and dopamine (DA). Such modulation effectively broadens the operational range in which specific neural circuits can function adaptively. This report discusses how these amines are themselves modulated; for example, by the steroid hormone 20-hydroxyecdysone (20-E) or by the addition of a second biogenic amine. Such second-order neuromodulation, termed metamodulation, is discussed in the context of two well-studied invertebrate systems: the tobacco hornworm moth Manduca sexta, a model of neurodevelopment and plasticity, and the medicinal leech Hirudo medicinalis, a long-favored preparation used to study neural circuits at the level of identified neurons. A portion of this article reviews our previous research of M. sexta that shows that the ‘preadult’ rise in 20-E is both necessary and sufficient for the increased levels of octopamine observed in the adult. Such elevated levels likely play an important role in the production and modulation of adult behaviors. The somatic growth of median octopaminergic neurons and the late expression of OA-immunoreactivity by novel lateral neurons are also demonstrated to be dependent on 20-E. New immunocytochemical results of stained dopaminergic neurons in the larval and adult moth brain are provided as well, and the potential influence of 20-E on the developmental expression of this neuromodulator is presented. Turning attention to the leech, data indicate that the actions of OA are dramatically altered when 5-HT is combined with OA in the bath surrounding the isolated nervous system. Although either OA or 5-HT alone induces fictive swimming behavior, a cocktail of these two amines strongly inhibits the generation of swimming. Subsequent removal of such a mixture induces nearly continuous swimming and constitutes the best swim-inducing stimulus encountered to date. To understand better how these nonadditive effects are achieved, new results are discussed that indicate that the leech brain is the target of metamodulation by the two amines. Both the arthropod and annelid systems presented here highlight the multiple levels of metamodulation that can exist in nervous systems, and the diverse ways that a modulator’s actions can become altered over short or long time periods.
PD and the Future: The Role of PD in the Overall Management of ESRD
Authors: Mendelssohn D.C.
Published: April 2003

Given the epidemic growth of ESRD and the high costs of dialysis therapy, there is an urgent need to define the optimal dialysis modality distribution. The factors influencing dialysis modality distribution are complex and not well understood. Based on survey results that have assessed the attitudes of nephrologists in Canada, the USA and the UK, it appears that there is underutilization of both peritoneal dialysis (PD) and home hemodialysis (HD) in these countries. Nephrologists have a positive attitude towards home therapies, and do not appear to be biased against PD. A planned approach to dialysis initiation, with active promotion of PD and home HD as the initial dialysis modality for suitable patients, would be expected to revive usage of home PD and allow for the emergence of daily home HD as a significant and exciting new modality.
Random Sample (DOPPS) versus Census-Based (Registry) Approaches to Kidney Disease Research
Authors: Port Friedrich K. , Wolfe Robert A. , Held Philip J. , Young Eric W.
Published: April 2003

This review describes advantages and limitations of registries that base their analyses on the census of all patients. Registries may utilize the random sample approach to enrich their data for more detailed and informative research. The Dialysis Outcomes and Practice Pattern Study (DOPPS) and its random sample approach is discussed here in detail, with examples on the value of this method. The DOPPS is currently being expanded to allow for even more valuable studies. This methodology can also be applied to large countries that do not have an existing registry, as it is an effective way of collecting detailed information at a relatively low cost that is representative of the country or population as a whole.
Current Studies on Oxidant Stress in Dialysis
Authors: Handelman Garry J.
Published: April 2003

Breath ethane measurements in hemodialysis indicate that a portion of these patients suffer increased oxidant stress, consistent with findings using other methods for oxidant stress determination. Loosely-bound iron definitely appears in the bloodstream when substantial doses of IV iron are administered, since transferrin is fully saturated, but our investigations generally do not show short-term oxidant stress from this treatment. If small doses of IV iron are utilized, transferrin saturation can be avoided, and risk is minimized. The vitamin C status of hemodialysis patients is usually lower than the general population, and the impact of this deficiency must be assessed in controlled investigations. Various interventions, including the vitamin E-bonded dialyzer and dietary antioxidant supplements, may ameliorate a portion of the oxidant stress in hemodialysis patients.
Fetal Blood Saturation during the 1st and 2nd Stage of Labor and Its Relation to the Neonatal Outcome
Authors: Leszczyńska-Gorzelak Bożena , Poniedziałek-Czajkowska Elżbieta , Oleszczuk Jan
Published: April 2003

Objective: The aim of this study was to evaluate fetal blood oxygenation (SpO2) by means of continuous pulse oximetry during labor and its relation to the neonatal outcome. Materials and Methods: Fetal SpO2 was measured continuously during labor with a noninvasive pulse oximetry for fetal application. The average, minimum and maximum SpO2 levels were evaluated separately for the 1st and 2nd stage of labor. The average SpO2 of the fetus was compared to the neonatal outcome assessed by the levels of pH, pO2 and pCO2 in the fetus’ umbilical blood and to the Apgar score. Results: Twenty-eight patients were monitored by fetal pulse oximetry. All the patients had normal, vaginal delivery. During the 1st stage of labor, the average fetal SpO2 was 51.78 ± 8.00%, the minimum SpO2 level was 37.61 ± 9.86%, and the maximum level of SpO2 was 63.82 ± 7.37%; in the 2nd stage of labor, the average SpO2 level was 44.91 ± 8.28%, the minimum level was 35.00 ± 9.22%, and the maximum SpO2 was 52.30 ± 9.36%. A significant decrease in the fetal average and maximum SpO2 levels was observed between the 1st and the 2nd stages of labor (the average SpO2 was 51.78 ± 8.00% vs. 44.91 ± 8.28%, p = 0.00029; the maximum SpO2 was 63.82 ± 7.37% vs. 52.30 ± 9.36%, p < 0.00001). A significant correlation between the average SpO2 level during the 1st and 2nd stage of labor and the Apgar score at the first minute of outcome was observed (R = 0.43, p = 0.031). No relationship between the fetal SpO2 during the 1st and the 2nd stage of labor and the pH, pCO2, and pO2 in the fetal umbilical blood were observed. Conclusions: During the 2nd stage of labor, a significant decrease in the fetus’ SpO2 can be observed. The fetus’ SpO2 level >30% in the 1st and 2nd stage of labor was related to the good neonatal outcome. The assessment of the fetal SpO2 during the 1st stage of labor seems to be important in predicting neonatal outcome.
Severe Allergy in a Pregnant Woman after Vaginal Examination with a Latex Glove
Authors: Shingai Yuri , Nakagawa Koji , Kato Takeshi , Fujioka Toru , Matsumoto Takashi , Kihana Toshimasa , Noda Kiyofumi , Mori Takashi
Published: April 2003

Recently case reports about latex allergy were increased. We have experienced severe latex allergy in a pregnant women after vaginal examination with a latex glove. A 33-year-old woman, 38 weeks pregenant, was hospitalized for management of fetal IUGR. She underwent a vaginal examination with a latex glove and soon developed severe anaphylactic reactions. Although two hours later her condition had remarkably improved, regular uterine contractions appeared, and fetal cardiotocogram showed late decelerations. So emergency cesarean section was performed under the situation without using any latex products. She delivered a male infant weighing 2,227 g (–2.21 SD) at 38 weeks gestation. His Apgar score was 5 points at 1 min and 8 points at 5 min. The latex-specific IgE of this patient was high and IgE for banana, avocado and kiwi were also positive. These foods showed cross-reactions with latex, but she had no history of allergic reactions against these foods. She had a history of atopic reactions and of atopic dermatitis while working as a nurse at the ICU. It is thought that this patient was in the high-risk group.
Pharmacokinetics of Caroverine in the Inner Ear and Its Effects on Cochlear Function after Systemic and Local Administrations in Guinea Pigs
Authors: Chen Zhiqiang , Duan Maoli , Lee Howsung , Ruan Runsheng , Ulfendahl Mats
Published: April 2003

Caroverine, an N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, has been shown to protect the inner ear from excitotoxicity and to be effective in the treatment of cochlear synaptic tinnitus. Local administration of caroverine on the round window membrane (RWM) could be a more effective means of administration to avoid systemic side/adverse effects. The present study investigates the pharmacokinetics of caroverine in the perilymph, cerebrospinal fluid (CSF) and plasma following intravenous and local applications at different dosages. High-performance liquid chromatography was used to determine the drug concentrations. Our results show much higher caroverine concentrations in the perilymph with lower concentrations in CSF and plasma following local applications compared with systemic administration. Auditory brainstem responses were measured to evaluate the changes in auditory function. The effects on hearing were transient and fully reversible 24 h after local caroverine applications. The findings suggest that local application of caroverine on the RWM for the treatment of excitotoxicity-related inner ear diseases, such as tinnitus and noise-induced hearing loss, might be both safe and more efficacious while avoiding high blood and CSF caroverine levels seen with systemic administration.
HIV: Epidemiology and Strategies for Therapy and Vaccination
Authors: Marcus Ulrich , Dittmar Matthias T. , Kräusslich Hans-Georg
Published: April 2003

In the decades since its discovery, the acquired immunodeficiency syndrome AIDS has developed into one of the leading causes of death worldwide, with a dramatic situation in many countries of subsaharan Africa. A large body of knowledge has been acquired regarding the molecular biology and replication properties of the causative agent of AIDS, the human immunodeficiency virus (HIV). However, despite these advances the global spread of HIV and especially its spread in developing countries continues almost unabated. During the last decade, drugs inhibiting HIV replication have been introduced into clinical use and highly active antiretroviral therapy (HAART) using a combination of several drugs has been proven to slow or halt the course of the disease in most patients. However, HAART is currently only available in countries of the developed world and the emergence of resistant variants may rapidly lead to a partial loss of this therapeutic arsenal. Thus, the development of a prophylactic vaccine against HIV must be the ultimate goal to control the global pandemic of AIDS. This minireview summarises the state of the epidemic and discusses current treatment strategies as well as future developments. Finally, strategies towards the development of a vaccine against HIV are presented and recent studies using prime-boost regimens to achieve protection from disease in animal models while not preventing infection with the challenge virus are discussed.
Generation of Recombinant Virus-Like Particles of Human and Non-Human Polyomaviruses in Yeast Saccharomyces cerevisiae
Authors: Sasnauskas K. , Bulavaite A. , Hale A. , Jin L. , Knowles W.A. , Gedvilaite A. , Dargevičiūte A. , Bartkevičiūte D. , Žvirblienė A. , Staniulis J. , Brown D.W.G. , Ulrich R.
Published: April 2003

Objectives: Non-viral methods of gene transfer have been preferred in gene therapy approaches for several reasons, particularly for their safety, simplicity and convenience in introducing heterologous DNA into cells. Polyomavirus virus-like particles (VLPs) represent a promising carrier for encapsidation of foreign nucleic acids for gene therapy. For the development of such gene delivery systems as well as for providing reagents for improving virus diagnostics, an efficient yeast expression system for the generation of different polyomavirus VLPs was established. Methods: A galactose-inducible Saccharomyces cerevisiae yeast expression system was used. Formation of empty VLPs was confirmed by cesium chloride ultracentrifugation, agarose gel electrophoresis and electron microscopy. Cross-reactivity of the major capsid proteins (VP1) of different polyomaviruses was analyzed by Western blot using rabbit and mice sera raised against the VP1 proteins. Results: VP1 of polyomaviruses from humans (JC polyomavirus and serotypes AS and SB of BK polyomavirus), rhesus monkeys (simian virus 40), hamsters (hamster polyomavirus), mice (murine polyomavirus) and birds (budgerigar fledgling disease virus) were expressed at high levels in yeast. Empty VLPs formed by all yeast-expressed VP1 proteins were dissociated into pentamers and reassociated into VLPs by defined ion and pH conditions. Different patterns of cross-reactivity of the VP1 proteins with heterologous mice and rabbit sera were observed. Conclusion: The developed heterologous yeast expression system is suitable for high-level production of polyomavirus VLPs. Yeast-derived VLPs are generally free of toxins, host cell DNA and proteins. These VLPs might be useful for the generation of new diagnostical tools, gene delivery systems and antiviral vaccines.
Review of an Inactivated Vaccine against Hantaviruses
Authors: Cho Hae-Wol , Howard Colin R. , Lee Ho-Wang
Published: April 2003

Objective: Hantaviruses cause haemorrhagic fever with renal syndrome and result in severe morbidity and mortality in humans. Safe and effective vaccines are needed to reduce the incidence of human illness. In this study, the immune response to an inactivated hantavirus vaccine was measured in 64 human volunteers for Hantavax® and 10 human volunteers for a Hantaan-Puumala virus combination vaccine at high risk of infection by virtue of their residence and occupation. Methods: A serum sample was obtained from each volunteer before the initial vaccination (day 0), 30 days after each inoculation and 1 year after the initial dose. All sera were kept at –20° until tested. IgG-specific antibody titres were tested by ELISA and immunofluorescence assay (IFA). Neutralizing antibody titres were determined by a plaque reduction neutralizing test. Results: Thirty days after vaccination, 79 and 62% of the subjects had developed a significant hantavirus antibody titre as measured by IFA and ELISA, respectively. Seroconversion rates increased to 97% 1 month after the booster dose. Neutralizing antibody titres paralleled this trend, with 13% of vaccine recipients producing neutralizing antibody 1 month after the first dose and 75% of vaccine recipients responding 1 month after boosting. Antibody titres had declined by 1 year, however, with only 37 and 43% of sera found to be positive by IFA and ELISA, respectively. Re-vaccination at this time produced a vigorous anamnestic response, with 94 and 100% of vaccine recipients yielding positive antibody titres. Only 50% of the sampled population, however, produced neutralizing antibodies following the booster dose 1 year later. Conclusions: The vaccine was well tolerated and there were no apparent differences in the responses in human subjects. However, further improvement of this vaccine is necessary in order to induce a longer-lasting humoral immune response.
Stop Codon Insertion Restores the Particle Formation Ability of Hepatitis B Virus Core-Hantavirus Nucleocapsid Protein Fusions
Authors: Kazaks Andris , Lachmann Sylvie , Koletzki Diana , Petrovskis Ivars , Dislers Andris , Ose Velta , Skrastina Dace , Gelderblom Hans R. , Lundkvist Åke , Meisel Helga , Borisova Galina , Krüger Detlev H. , Pumpens Paul , Ulrich Rainer
Published: April 2003

In recent years, epitopes of various origin have been inserted into the core protein of hepatitis B virus (HBc), allowing the formation of chimeric HBc particles. Although the C-terminus of a C-terminally truncated HBc (HBcΔ) tolerates the insertion of extended foreign sequences, the insertion capacity is still a limiting factor for the construction of multivalent vaccines. Previously, we described a new system to generate HBcΔ mosaic particles based on a read-through mechanism in an Escherichia coli suppressor strain [J Gen Virol 1997;78:2049–2053]. Those mosaic particles allowed the insertion of a 114-amino acid (aa)-long segment of a Puumala hantavirus (PUUV) nucleocapsid (N) protein. To study the value and the potential limitations of the mosaic approach in more detail, we investigated the assembly capacity of ‘non-mosaic’ HBcΔ fusion proteins and the corresponding mosaic constructs carrying 94, 213 and 433 aa of the hantaviral N protein. Whereas the fusion proteins carrying 94, 114, 213 or 433 aa were not assembled into HBcΔ particles, or only at a low yield, the insertion of a stop codon-bearing linker restored the ability to form particles with 94, 114 and 213 foreign aa. The mosaic particles formed exhibited PUUV-N protein antigenicity. Immunization of BALB/c mice with these mosaic particles carrying PUUV-N protein aa 1–114, aa 1–213 and aa 340–433, respectively, induced HBc-specific antibodies, whereas PUUV-N protein-specific antibodies were detected only in mice immunized with particles carrying N-terminal aa 1–114 or aa 1–213 of the N protein. Both the anti-HBc and anti-PUUV antibody responses were IgG1 dominated. In conclusion, stop codon suppression allows the formation of mosaic core particles carrying large-sized and ‘problematic’, e.g. hydrophobic, hantavirus sequences.
Lip and Tongue Function Differently Affected in Individuals with Multiple Sclerosis
Authors: Hartelius Lena , Lillvik Malin
Published: April 2003

Clinical dysarthria test scores on lip function and tongue function were compared for 77 dysarthric as well as non-dysarthric subjects with multiple sclerosis (MS) and 15 control subjects. Results show that tongue function was significantly more severely affected than lip function in individuals with MS. Furthermore, tongue function, but not lip function, was significantly more severely affected in the MS individuals with no dysarthria compared to the control group. Test items requiring increased rate of movement (oral and verbal diadochokinesis) were significantly more severely affected than the items requiring range and force of movement, but only in the dysarthric MS subgroup. Moderate correlations were found between tongue and lip function and neurological deficit scores, number of years in disease progression, and perceptually perceived consonant and vowel precision. Consequently, tongue dysfunction can be detected clinically and subclinically using a dysarthria test procedure, and as an early sign of articulatory dysfunction it should be an early target in therapeutic interventions.
Autoantibodies to CD69 in Patients with Chronic Hepatitis Type C: A Candidate Marker for Predicting the Response to Interferon Therapy
Authors: Okamoto Nahoko , Yotsuyanagi Hiroshi , Ooka Seido , Matsui Toshihiro , Suzuki Kurokawa Manae , Suzuki Michihiro , Iino Shiro , Nishioka Kusuki , Kato Tomohiro
Published: April 2003

Objective: To understand the autoimmunity associated with chronic hepatitis C (CHC), we investigated autoantibodies (autoAbs) to CD69. Methods: With this aim, we tested the reactivity of serum samples from patients with CHC and asymptomatic carriers of hepatitis C virus (HCV), as well as from patients with chronic hepatitis B (CHB) and autoimmune hepatitis (AIH), to recombinant CD69 molecules. Results: Frequencies of anti-CD69 autoAbs were 38.7% in CHC, 15.8% in AIH and 12.3% in CHB. None of the tested asymptomatic HCV carriers had autoAbs to CD69. It is important clinically that the presence of anti-CD69 autoAbs was found to be associated with a poor response to interferon-α (IFN-α) therapy. In the epitope analysis, multiple epitopes were mapped on CD69, indicating antigen-driven production of the autoAbs. Conclusion: We evidenced existence of anti-CD69 autoAbs in patients with CHC, and found that the anti-CD69 autoAb may have potential for predicting responses to IFN-α therapy.
Effects of Free Radicals on Coronary Artery
Authors: Walia Mandeep , Kwan Chiu-Yin , Grover Ashok K.
Published: April 2003

Coronary arteries supply blood to the heart and hence the control of coronary tone is pivotal to human survival. Reactive oxygen species (ROS) in specified amounts play an important role in normal metabolic and signalling processes. However, excess ROS can cause severe cardiovascular damage. For example, NO is produced by endothelium as a signal for relaxation. However, in an inflammatory response, NO from endothelium or macrophages can combine with superoxide to produce more deleterious peroxynitrite. Excess ROS have been associated with loss of coronary artery pliability – loss of contraction in some instances and relaxation in others. Atherosclerosis may also be considered an inflammatory response that leads to artery blockage, coronary disease and ischaemia-reperfusion. ROS produce various types of damage to ion channels and pumps and this damage is associated with vascular diseases such as atherosclerosis and hypertension. Endothelium and smooth muscle in the coronary artery are also affected differently by individual ROS. In fact, endothelium may act to protect the underlying smooth muscle against ROS. This review will give an overview of this field.
Sperm Retrieval Procedures and Intracytoplasmatic Spermatozoa Injection with Epididymal and Testicular Sperms
Authors: Schwarzer J. Ullrich , Fiedler Klaus , v. Hertwig Irene , Krüsmann Gottfried , Würfel Wolfgang , Schleyer Manfred , Mühlen Bärbel , Pickl Ulrich , Löchner-Ernst Dieter
Published: April 2003

Introduction: Male infertility caused by azoospermia due to non-reconstructable obstruction or non-obstructive azoospermia can be treated by microsurgical epididymal aspiration (MESA) or testicular sperm extraction (TESE) followed by an intracytoplasmatic spermatozoa injection (ICSI). Material and Methods: From 9/93 to 6/01, we carried out 1,025 ICSI procedures with aspirated epididymal or testicular sperms in 684 cases. 163 ICSI cycles were performed with epididymal sperms and 862 ICSI cycles with testicular sperms or spermatids. The TESE was carried out by open biopsy, frequently in a multilocular technique. The aspirated spermatozoas were used after cryopreservation (frozen) or immediately after aspiration (fresh). Results: 538 patients had obstructive azoospermia or ejaculation failure. In 487 cases the underlying cause of azoospermia was an impaired spermatogenesis, following maldescensus testis, chemotherapy, radiotherapy, or caused by Sertoli-cell-only syndrome, a genetic disorder or an unknown etiology. The transfer rates, pregnancy rates and birth rates per ICSI cycle showed no statistically significant differences between testicular and epididymal sperms in the cases of seminal obstruction (28% average birth rates in both cases). However, highly significant was the difference in birth rates with regard to the underlying cause of infertility. In contrast, in treating non-obstructive azoospermia we observed a birth rate of 19% per cycle. In all patient groups the birth rate with fresh spermatozoas did not differ from those with cryopreserved spermatozoa. 40% of patients after multilocular TESE showed clinical signs of testicular lesion. Conclusion: The underlying cause of azoospermia is the most important factor for the outcome of ICSI using epididymal and testicular sperms. In cases of non-obstructive azoospermia, the pregnancy rate is low compared with the results in cases of obstructive azoospermia. There is no difference between fresh and cryopreserved sperms. TESE with ICSI is the most efficient treatment of azoospermia caused by hypergonadotropic hypogonadism. The morbidity of the TESE procedure is highly relevant and must be considered if this technique is indicated.
Establishment of the Mouse as a Model Animal for the Study of Diabetic Cataracts
Authors: Hegde K.R. , Henein M.G. , Varma S.D.
Published: April 2003

The purpose of the present study was to investigate the suitability of using the mouse, a species known to have a low lens aldose reductase activity, as a model animal for studying the pathogenesis of diabetic cataract. Earlier studies with diabetic rats whose cataract development is much faster can only partially explain the etiology of cataracts in humans where lens aldose reductase is substantially low. CD-1 mice were injected intraperitoneally with streptozotocin according to Rossini’s method. Blood glucose levels were estimated after 7 days, and animals having blood glucose between 300 and 400 mg/dl were selected for further experiments. Development of lenticular opacity was followed by examining the animals every 3–4 weeks by direct ophthalmoscopy, slitlamp examination and Scheimpflug photography. Additionally, the animals were sacrificed at appropriate intervals, eyes enucleated and subjected to morphological studies. The presence of refractive changes and early cataract in the diabetic mice was initially ascertained by the distorted appearance of the grid pattern when seen through the isolated lenses. Early cataracts were visible on slitlamp examination and by ophthalmoscopy as early as 3–4 weeks after the establishment of diabetes. Advanced opacity was clearly documentable by photography after 5–6 months. Similar to that in other species, a single layer of anterior epithelial cells abutting the anterior capsule was seen in the histological sections of normal mouse lenses. On the contrary, the epithelium in the diabetic lens was multilayered, and numerous nucleated cells were visible in the superficial anterior cortex. These studies therefore suggest that further studies with mice may throw additional light on the contribution of diabetes in the pathogenesis of cataracts in low lens aldose reductase models.
Contents of the Cochrane Library on the Organisation of Stroke Services
Authors: Sandercock Peter
Published: April 2003

Background: The Cochrane Collaboration is an international organisation that aims to help people make well-informed decisions about healthcare by preparing, maintaining and promoting the accessibility of systematic reviews of the effects of healthcare interventions. This paper briefly summarises the output of the Cochrane Stroke Group in relation to evaluating different forms of the organisation of services for patients with stroke. Methods: A survey of randomised controlled trials and systematic reviews (and meta-analyses) of randomised controlled trials. Results: Issue 2 of the Cochrane Library 2002 includes 1,377 completed systematic reviews and 1,055 protocols for reviews in progress. The Cochrane Controlled Trials Register included 343,270 reports of randomised or controlled clinical trials. The Cochrane Stroke Review Group had contributed 63 completed systematic reviews, 29 protocols of reviews in progress, and 4,396 reports of stroke trials. The main published reviews relevant to entire services related to: stroke units; services for helping acute stroke patients avoid hospital admission; services for reducing duration of hospital care for acute stroke patients; care pathways for stroke. Main Conclusions: There has been a rapid recent growth in the evidence base on stroke care. Systematic reviews of several aspects of stroke services are now published and other reviews are in progress. For areas where no reviews have been completed, the Cochrane Library includes a substantial number of individual randomised trials evaluating the effects of specific services and components of services.
Removal of the Shell Coat Affects Maintenance of Epithelia in Blastocysts of the Brushtail Possum in vitro
Authors: Casey Nicholas , Selwood Lynne
Published: April 2003

The aim of the present study was to investigate the role of the marsupial shell coat in embryonic development because it may be a potential target for immunocontraceptive control of the brushtail possum. Conceptuses from 52 female possums were collected between 1995 and 1997 in New Zealand and Australia. Development was examined in representative stages from cleavage to the early trilaminar blastocyst. The effect of coat removal by microdissection was examined by comparing development in vivo (n = 29), with development in vitro, both with (n = 10) and without (n = 13) shell coat removal. Conceptuses were monitored and photographed in culture, fixed and examined by transmission electron microscopy. The ultrastructure of uni-, bi- and trilaminar blastocyst stages in vivo and in vitro and of the early stages of hypoblast and embryonic endoderm formation are described for the first time in the possum. Shell coat removal had little impact on most cleavage stages, as the intact mucoid coat appeared to provide structural support to the embryo. Common features of unilaminar coat-free specimens after culture were rounding up and detachment of cells from the blastocyst epithelium and the loss of cell surface projections. The most remarkable features of the shell-free trilaminar blastocysts in comparison with the in vivo and in vitro controls were the hydration of many cells, and the large-scale disruption and modification of numerous epithelia, particularly of the younger, or newly forming populations. The shell appears to be functionally important after blastocyst formation, particularly after breakdown of the mucoid coat. After shell removal, conceptus response in vitro suggested that the shell played a role in maintaining structural integrity. The shell was found to be necessary for normal embryonic development.
Vitamin A, Vitamin E, Selenium, and Zinc Blood Levels in Patients with Benign Epithelial Hyperplastic Lesions and in Patients with Squamous Cell Carcinoma of the Vocal Folds
Authors: Habermann W. , Swanston H. , Crevenna R. , Luxenberger W. , Friedrich G.
Published: April 2003

Objectives: The purpose of this study was to compare the blood levels of vitamin A, vitamin E, selenium, and zinc among patients with nonepithelial voice disorders, benign epithelial hyperplastic lesions, and squamous cell carcinomas and to investigate factors related to the presence of carcinomas. Patients and Methods: 139 consecutive patients (73 males and 66 females) with chronic voice disorders were examined by videolaryngoscopy and biopsy (where necessary). The subject’s smoking habits, alcohol consumption, and nutrition habits were obtained from questionnaires, and blood levels of vitamin A, vitamin E, selenium and zinc were analyzed. Blood levels of antioxidants were categorized according to whether they were in the normal range or not. Results: There was a significant association between diagnostic category and whether or not selenium levels were in the normal range (p = 0.02). However, there were no significant relationships between diagnostic group and whether blood levels of vitamin A, vitamin E, and zinc were in the normal range. Males (p < 0.001) and elderly subjects (p = 0.02) were more likely to be in the more serious diagnostic groups. There were also significant relationships between diagnostic group and smoking (p < 0.001), drinking alcohol (p < 0.001), eating spicy foods (p = 0.03), and eating fatty or smoked foods (p = 0.004). Conclusions: Lifestyle choices such as smoking, drinking alcohol and eating fatty and spicy foods were significantly related to having a more serious diagnosis. Selenium levels were significantly associated with diagnosis, however, this study does not provide conclusive evidence that selenium is protective against laryngeal cancer. Until there is further evidence, changes to patients’ lifestyles should be more strongly encouraged than the taking of selenium supplements owing to the danger associated with selenium toxicity in case of overload.
Unusual Multiple Giant Tonsillolith
Authors: Doğru Harun , Tüz Mustafa , Ayçiçek Abdullah
Published: April 2003

Tonsillar concretions may frequently be seen in clinical practice but it is very uncommon to encounter clinically significant tonsilloliths. Tonsilloliths particularly deep located, should be considered when encountered with unilateral tonsillar hypertrophy and during the management period, it should be kept in mind that tonsilloliths may be multiple. We present a case of a giant tonsillolith concurrent with two more minor tonsilloliths.
Sequence Analysis of COL1A1 and COL1A2 Genes in Clinical Otosclerosis: No Evidence for Mutations in the Coding Regions of the Genes
Authors: McKenna Michael J. , Kristiansen Arthur G. , Körkkö Jarmo
Published: April 2003

Because of the clinical and histopathologic similarities between otosclerosis and type I osteogenesis imperfecta and prior evidence that some cases of clinical otosclerosis have reduced expression of one COL1A1 allele, we analyzed the COL1A1 and COL1A2 genes in 10 patients with clinical otosclerosis, including 2 patients with reduced or null expression of one COL1A1 allele. Conformation-sensitive gel electrophoresis of all exons and flanking sequences and the promoter sequences for each gene were performed. There were no mutations found in the coding or promoter sequence of either gene in any of the cases examined. One case with reduced allelic expression revealed evidence of a possible splicing mutation at intervening sequence intron 44+4. The second case of reduced allelic expression failed to demonstrate evidence for mutations in the coding or splice site regions of the COL1A1 gene, suggesting a different mechanism for reduced allelic expression than that which has been observed thus far in type I osteogenesis imperfecta.
Swallowing Dysfunction as Long-Time Complication of Neck Surgery and Trauma
Authors: Schneider Berit , Denk Doris-Maria , Bigenzahn Wolfgang
Published: April 2003

Introduction: Swallowing impairments are common problems in daily otorhinolaryngological practice. One of the keys to normal swallowing is the ability to move the larynx vertically. This ability can be affected by surgical intervention or trauma of the anterior neck. The symptoms range from self-limited dysphagia/dysphonia caused by pain or swelling to more serious permanent symptoms after neck surgery or trauma. Objective: To illustrate the relationship between wound healing with scarring and contraction of the soft tissue and consecutive swallowing impairments as late postsurgical consequences after neck surgery or open trauma, especially in the pretracheal and prelaryngeal soft tissue region. The reduced laryngeal elevation due to fixating postoperative scarring after surgical intervention of the anterior neck will be discussed on the basis of 6 selected cases. Results: A relief of the impairments and an improvement or normalization of the voice and swallowing function can be achieved by surgical extirpation and mobilization of cicatricial tissue. Conclusions: This implies that a surgical intervention or an open trauma of the anterior neck can lead to a cicatricial fixation of the larynx, which has to be considered as a potential cause of dysphagia. Postoperative diagnostics and treatment should therefore include the consideration of swallowing dysfunction as late consequences of neck surgery or open larynx trauma.
Reduction of Allergic Skin Responses and Serum Allergen-Specific IgE and IgE-Inducing Cytokines by Drinking Deep-Sea Water in Patients with Allergic Rhinitis
Authors: Kimata Hajime , Tai Hideyuki , Nakajima Hiroshi
Published: April 2003

Deep-sea water intake reduces allergic skin responses and serum levels of total IgE, Japanese cedar pollen-specific IgE, interleukin (IL)-4, IL-6, IL-13, and IL-18 in patients with allergic rhinitis, while distilled water intake fails to do so.
Pharmacology and Physiology of Ovine Corticosteroid Receptors
Authors: Richards Elaine M. , Hua Yi , Keller-Wood Maureen
Published: April 2003

The aim of these studies was to characterize the ovine corticosteroid receptors (MR, mineralocorticoid receptors and GR, glucocorticoid receptors) in ovine hippocampus and brainstem. Adrenal-intact and adrenalectomized ewes were studied; adrenalectomized ewes were killed 47 ± 9 h after steroid withdrawal, when symptoms of hypotension and/or hyperkalemia became evident. RT-PCR, immunoblotting and pharmacologic studies indicated the presence of both MR and GR in hippocampus and brainstem. Competitive binding studies using 3H-cortisol in brain tissue showed that the ovine MR binds cortisol, aldosterone and progesterone with equal affinity. Differences in receptor availability in intact and adrenalectomized ewes, along with determination of the binding affinity (Kd) of MR and GR, suggested that MR occupancy is about 90%, whereas GR occupancy is about 30%, in normal animals. There was a significant increase in protein level of MR in brainstem, and the appearance of a higher molecular weight band for MR in hippocampus following steroid withdrawal, however no significant change in mRNA was detected by semiquantitative RT-PCR for either MR or GR in hippocampus or brainstem following steroid withdrawal. These studies suggest that physiological ligands of MR in the sheep brain include progesterone and cortisol, and that, as in other species, affinity of MR for cortisol is greater than that of GR.
On Vowel Height and Consonantal Voicing Effects: Data from Italian
Authors: Esposito Anna
Published: April 2003

This paper reports an acoustic study of CV sequences in Italian (where C is /b, d, g, p, t, k/ and V is one of the seven Italian vowels in stressed position). It explores the effects of vowel height, consonantal voicing, and place of articulation on a number of acoustic attributes of vowels (duration, f₀, F1), and on the duration of the preceding stop closure, VOT and RVOT (defined as the interval from C release to the acoustic vowel onset). The aim is to provide, for Italian, a comprehensive account of all the various interactions between consonantal voicing, vowel height and consonant place on the above acoustic attributes in order to propose an explanation for such effects, and to compare the present results and interpretations with previous explanations and with previous data on Italian and other languages.
Gastric Electrical Stimulation in Intractable Symptomatic Gastroparesis
Authors: Abell Thomas L. , van Cutsem Eric , Abrahamsson Hasse , Huizinga Jan D. , Konturek J.W. , Galmiche Jean Paul , VoelIer Guy , Filez Ludo , Everts Bernt , Waterfall William E. , Domschke W. , Bruley des Varannes Stanislas , Familoni Babajide O. , Bourgeois Ivan M. , Janssens Jozef , Tougas Gervais
Published: April 2003

Background: The treatment of gastroparesis remains unsatisfactory despite prokinetic and anti-emetic drugs. Gastric electrical stimulation has been proposed as a therapeutic option. We have assessed the effect of gastric electrical stimulation on symptoms, medical treatment, body weight and gastric emptying in patients with intractable symptomatic gastroparesis in a non-placebo-controlled study. Methods: In this multicenter study, 38 highly symptomatic patients with drug-refractory gastroparesis were enrolled. Patients first received temporary electrical stimulation using percutaneous electrodes. The 33 responders to temporary stimulation then underwent surgical implantation of a permanent stimulator. Severity of vomiting and nausea was assessed before and after stimulation. Patients were reassessed 3, 6, and 12 months after permanent implantation. Results: With stimulation, 35/38 patients (97%) experienced >80% reduction in vomiting and nausea. This effect persisted throughout the observation period (2.9–15.6 months, 341 patient-months). Gastric emptying did not initially change, but improved in most patients at 12 months. At 1 year, the average weight gain was 5.5% and 9/14 patients initially receiving enteral or parenteral nutrition were able to discontinue it. Conclusion: Electrical stimulation of the stomach has an immediate and potent anti-emetic effect. It offers a safe and effective alternative for patients with intractable symptomatic gastroparesis.
Prospective Comparison of Endoscopy, Endosonography and Computed Tomography for Staging of Tumours of the Oesophagus and Gastric Cardia
Authors: Kienle Peter , Buhl Klaus , Kuntz Christian , Düx Markus , Hartmann Christine , Axel Benner , Herfarth Christian , Lehnert Thomas
Published: April 2003

Background: Local and multimodal therapeutic strategies for tumours of the oesophagus and gastric cardia, require precise preoperative staging. Endosonography is considered the most accurate staging method, while computed tomography (CT) has limitations especially in the evaluation of local infiltration. Macroscopic endoscopic evaluation was reported to be accurate in selected series, but no study has yet compared all three staging modalities. Methods: One hundred and seventeen unselected patients with tumours of the oesophagus and gastric cardia were prospectively staged first by the endoscopic macroscopic appearance and then by endosonography. All patients had preoperative CT scans, however, only the 36 patients receiving the scans at our institution were included in the study. The preoperative staging results were then compared to postoperative histology which was available as the gold standard in all included patients. Kappa statistics were used to exclude chance agreement of the clinical staging results with the pathohistological findings. Differences between the resulting ĸ values for the different staging modalities were analysed with a jack-knife test. Results: Endoscopic macroscopic staging and endosonography (accuracy 67 and 69%, weighted ĸ 0.78 and 0.84) were significantly more accurate than CT (accuracy 33%, weighted ĸ 0.44) for determination of the T category (p = 0.006 and p = 0.001). After exclusion of tumours of the cardia (n = 33), the accuracy of macroscopic and endosonographic staging (accuracy 72 and 75%, weighted ĸ 0.86 and 0.88) increased and remained more accurate than CT (accuracy 50%, weighted ĸ 0.62). The main pitfall in our series in staging the T category was the overestimation of T2 tumours in the cardia as T3 or even as T4 tumours due to the inability to visualise the serosa. The accuracy of predicting lymph node metastasis was 68% for macroscopic endoscopic, 79% for endosonographic, and 67% for CT staging. Only endosonographic staging was significantly different from chance agreement with histology (weighted ĸ = 0.56). Endosonographic staging was significantly more accurate than endoscopic macroscopic and CT staging (p = 0.03). Conclusions: Endosonography is the most accurate staging modality for overall preoperative staging of oesophageal and cardial tumours. Endoscopic macroscopic staging allows a reasonably accurate assessment of the T category.
Mesenteric Inflammatory Veno-Occlusive Disease: A Rare Cause of Intestinal Ischemia
Authors: Tempia-Caliera A.A. , Renzulli P. , Z’graggen K. , Lehmann T. , Ruchti C. , Büchler M.W.
Published: April 2003

Background: Mesenteric inflammatory veno-occlusive disease (MIVOD) is a rare cause of intestinal ischemia of unknown etiology. Histologically, MIVOD is characterized by extended thrombophlebitis and fibrous organized thrombosis of multiple veins. The arteries are by definition not involved. Management includes surgery in all cases described. Recurrence has not been described until now. Methods: We describe the case of a 64-year-old woman operated with the suspicion of intestinal ischemia. Clinical and histopathological characteristics are reported. Results: The patient underwent a right hemicolectomy and segmental resection of the terminal ileum 15 months later for a recurrence. The histological examination of the resected specimen confirmed the diagnosis of MIVOD and a recurrence thereof. Conclusion: MIVOD is a rare cause of colonic ischemia. Recurrence of the disease, which is described here for the first time, is unusual after surgical resection.
Substance P-Immunoreactive Nerves in Endobronchial Biopsies in Cough-Variant Asthma and Classic Asthma
Authors: Lee Sang Yeub , Kim Min Kyung , Shin Chol , Shim Jae Jeong , Kim Han Kyeom , Kang Kyung Ho , Yoo Se Hwa , In Kwang Ho
Published: April 2003

Background: Unlike classic asthma, cough-variant asthma does not show any evidence of airway obstruction. The main symptom is a dry cough with little known pathophysiology. Hypersensitivity of the cough receptors in cough-variant asthma and an increase in the sensory nerve density of the airway epithelium in persistent dry cough patients have been reported. Therefore, it is possible that there is a higher sensory nerve density in cough-variant asthma patients than in classic asthma patients. Objectives: This study was undertaken to compare the substance P (SP)-immunoreactive nerve density in mucosal biopsies of cough-variant asthma patients, classic asthma patients, and in control subjects. Methods: Bronchoscopic biopsies were performed in 6 cough-variant asthma patients, 14 classic asthma patients, and 5 normal controls. The tissues obtained were stained immunohistochemically. The SP-immunoreactive nerve density was measured in the bronchial epithelium using a light microscope at 400× magnification. Results: SP- immunoreactive nerve density for the cough-variant asthma group was significantly higher than that of the classic asthma group (p = 0.001), and of the normal control group (p = 0.006). Conclusions: It is possible that a sensory nerve abnormality within the airway may be related to hypersensitivity of the cough receptor, and that this may be one of the pathophysiologies of cough-variant asthma.