bluuebunny/crossref_metadata_2025 huggingface dataset:
5-Fluorouracil Administered as a 48-Hour Chronomodulated Infusion in Combination with Leucovorin and Cisplatin: A Randomized Phase II Study in Metastatic Colorectal Cancer
Authors: Falcone Alfredo , Allegrini Giacomo , Masi Gianluca , Lencioni Monica , Pfanner Elisabetta , Brunetti Isa , Danesi Romano , Bocci Guido , Del Tacca Mario , Conte Pierfranco
Published: April 2003

Objective: The primary objective of this trial was to determine the objective response of two regimens with CDDP administered every 2 weeks immediately before or after an ‘optimal’ 48-hour chronomodulated infusion of 5-fluorouracil (5-FU) modulated with leucovorin (LV) in metastatic colorectal cancer patients. Secondary endpoints were toxicity, 5-FU and its metabolites, plasma pharmacokinetics and progression-free and overall survival. Methods: Metastatic colorectal cancer patients with measurable disease who were chemotherapy-naive or pretreated only with a 5-FU-bolus-based chemotherapy were eligible for this study. The study was designed as a randomized phase II clinical trial. Results: Eighty-three patients were entered into the study. Forty-two were randomized to CDDP given before 5-FU and 41 to CDDP given after 5-FU. Patient characteristics were similar among the two groups. Toxicities were also similar among the two arms and the most frequent WHO grade III–IV toxicities were stomatitis (14%) and neutropenia (39–50%). Plasma pharmacokinetic profiles of 5-FU and 5-FUH2 were not significantly affected by the sequence of CDDP and 5-FU administration. Antitumor activity was similar in the two arms and was very promising both in pretreated patients (response rate 29%; 95% confidence interval 15–46%) and in chemotherapy-naive patients (response rate 56%, complete response 9%, 95% confidence interval 40–71%). Median survival of the patients with and without pretreatment was 12 and 16 months, respectively. Conclusions: These results do not suggest a sequence dependence of the synergism between CDDP and 5-FU. However, they challenge the need of oxaliplatin to improve 5-FU/LV activity in advanced colorectal cancer. In fact, our results with an ‘optimal’ 5-FU dose and scheduling are very similar to those obtained with oxaliplatin plus 5-FU/LV. However, only a randomized phase III study will be able to give an answer to the hypotheses raised by this study.
Clinical Value of Thymidine Kinase in Patients with Cervical Carcinoma
Authors: Fujiwaki Ritsuto , Hata Kohkichi , Moriyama Masashi , Iwanari Osamu , Katabuchi Hidetaka , Okamura Hitoshi , Miyazaki Kohji
Published: April 2003

Objective: Our purpose was to determine the clinical value of thymidine kinase (TK), which is an important pyrimidine pathway enzyme involved in salvage DNA synthesis, in patients with cervical carcinoma. Methods: We examined TK mRNA expression by reverse transcription polymerase chain reaction in 19 tissue specimens of invasive cervical carcinoma and 9 normal cervices and related it to thymidylate synthase (TS) and thymidine phosphorylase (TP) mRNA expressions. Serum TK level was determined by radioenzymatic assay in 79 patients with invasive cervical carcinoma, 7 patients with microinvasive carcinoma, 21 patients with carcinoma in situ and 32 normal women. Results: TK mRNA expression was upregulated in invasive cervical carcinoma compared with the normal cervix (p < 0.05) and significantly correlated with TS mRNA expression (p < 0.0001) but not with TP mRNA expression. The serum TK level was significantly higher in patients with invasive carcinoma than in normal women and patients with carcinoma in situ (p < 0.01 and p < 0.05). In patients with invasive cervical carcinoma, the serum TK level significantly correlated with TK mRNA expression (p < 0.05), but not with any conventional clinicopathologic factors. High serum TK levels significantly correlated with a poorer survival (p < 0.05), and multivariate analysis showed serum TK level to be an independent prognostic factor (p < 0.05). Conclusion: TK may play an important role in influencing the malignant behavior of cervical carcinoma, and measurement of the serum TK level may be useful in predicting survival in patients with cervical carcinoma.
Clinicopathologic Correlation of Serum Tissue Polypeptide Specific Antigen in Hepatocellular Carcinoma
Authors: Yao Wei-Jen , Chang Ting-Tsung , Wang Shan-Tair , Chow Nan-Haw , Lin Pin-Wen , Chang Yu-Chung , Tu Dom-Gene , Chiu Nan-Tsing
Published: April 2003

Objective: Recently, tissue polypeptide specific antigen (TPS) has been introduced as a cell proliferation marker. Little is known about its clinical significance in hepatocellular carcinoma (HCC). This study aimed to clarify serum TPS levels and tumor invasiveness of HCC. Methods: Serum TPS levels were determined with a monoclonal TPS IRMA assay in 69 patients with HCC. A correlation between serum TPS levels and clinical, biochemical, and pathological features was sought and compared with that of α-fetoprotein (AFP). In 57 healthy subjects, 56 patients with biopsy-proven chronic hepatitis and in 49 patients with liver cirrhosis, serum TPS levels were assayed and compared. Results: Serum TPS levels were significantly correlated with glutamic oxalacetic transaminase (p < 0.0001), glutamic pyruvic transaminase (p < 0.001), and lactate dehydrogenase (p = 0.027). There tended to be a positive relationship between serum TPS levels and tumor size, histological differentiation, capsular invasion, portal invasion, and clinical staging, although it did not reach statistical significance. A significant correlation, however, was observed between AFP and tumor size (p = 0.01), number (p = 0.042), histological grading (p = 0.028), portal invasion (p = 0.009), and clinical staging (p = 0.03). Patients with HCC had significantly higher TPS than healthy subjects (p < 0.001). However, there was substantial overlap between patients with HCC, chronic hepatitis, and liver cirrhosis. Conclusions: Our data suggest that serum TPS is not significantly related to tumor invasiveness in patients with HCC. Serum TPS levels are affected by the proliferative activity of the underlying chronic liver disease, which is frequently associated with HCC in Chinese patients. As a cell proliferation marker, serum TPS should be interpreted cautiously in the presence of chronic liver disease.
Inoculation of Human Interleukin-17 Gene-Transfected Meth-A Fibrosarcoma Cells Induces T Cell-Dependent Tumor-Specific Immunity in Mice
Authors: Hirahara Noriyuki , Nio Yoshinori , Sasaki Susumu , Minari Yoshimitu , Takamura Michio , Iguchi Chikage , Dong Ming , Yamasawa Kunihiro , Tamura Katsuhiro
Published: April 2003

Objective: The biological activities of interleukin-17 (IL-17), a newly cloned cytokine, have not been fully elucidated. The present study was designed to assess the in vitro and in vivo effect of transfecting the IL-17 gene into tumor cells. Methods: A complementary DNA (cDNA) encoding human IL-17 (hIL-17) was obtained by polymerase chain reaction amplification from the human CD4+ T cell cDNA library and inserted into the plasmid pRc/cytomegalovirus to construct an expression vector for the hIL-17 gene. Murine Meth-A fibrosarcoma cells were transfected with the hIL-17 gene using the lipofectin method. The hIL-17 gene-expressing clone (Meth-A/IL-17) was selected and analyzed for cytokine expression by Northern blot. Results: There was no significant difference in the in vitro proliferation rate among parent Meth-A, cells transfected with vector alone and Meth-A/IL-17 cells. When the tumor cells were transplanted subcutaneously into BALB/c nude (nu+/nu+) mice, there was no difference in in vivo growth rates among the three cell lines. Challenge with tumor cells in conventional BALB/c mice, however, resulted in the rejection of Meth-A/IL-17 cells, but the other two lines did grow. After immunization with Meth-A/IL-17 cells, the mice were rechallenged by parent Meth-A or syngeneic MOPC-104E plasmacytoma cells; the immunized mice rejected the Meth-A cells, but not the MOPC-104E cells. Injecting the anti-thy 1,2 (CD90), anti-CD4 or anti-CD8 monoclonal antibody into conventional BALB/c mice resulted in the resumption of in vivo growth of Meth-A/IL-17 cells, but injecting the anti-asialo GM1 antibody did not. Furthermore, flow cytometric analysis demonstrated a significant increase in the expression of major histocompatibility complex (MHC) class I and class II antigens and lymphocyte function-associated antigen-1 on Meth-A/IL-17 cells. Conclusion: Meth-A cells transfected with the hIL-17 gene can induce tumor-specific antitumor immunity by augmenting the expression of MHC class I and II antigens, and both CD4+ and CD8+ T cells may play important roles in inducing antitumor immunity, suggesting the possibility of developing a tumor vaccine incorporating IL-17-transfected tumor cells.
Chemotherapy for a Patient with Advanced Non-Small-Cell Lung Cancer during Pregnancy: A Case Report and a Review of Chemotherapy Treatment during Pregnancy
Authors: Jänne Pasi A. , Rodriguez-Thompson Diana , Metcalf Dianne R. , Swanson Scott J. , Greisman Harvey A. , Wilkins-Haug Louise , Johnson Bruce E.
Published: April 2003

Background: Lung cancer is the most common cause of cancer death in women in the USA. Lung cancer arising during pregnancy is rare and has been reported only 15 times since the 1950s. However, the use of chemotherapy for lung cancer during pregnancy has not previously been reported. Methods: The history, treatment and outcome of a patient with stage IV non-small-cell lung carcinoma (NSCLC) diagnosed during pregnancy is presented. Previous published reports on lung cancer were retrieved by a literature search of Medline and Cancerlit. Results: A 31-year-old woman was diagnosed as having stage IV NSCLC with bilateral pulmonary involvement when 26 weeks pregnant. Her shortness of breath progressed to dyspnea at rest on 100% inspired oxygen. Therefore, she was treated with systemic chemotherapy using cisplatin and vinorelbine. Despite this treatment, her oxygenation declined further over the next 4 days and thus the baby was delivered via cesarean section after 27 weeks of gestation. Four cycles of vinorelbine and cisplatin have now been administered. Following this treatment, the patient has experienced a significant clinical improvement and no longer requires supplemental oxygen. No chemotherapy-related adverse effects have been noted in the baby. In the 15 previously reported patients with concurrent lung cancer and pregnancy, chemotherapy administration during pregnancy has not been described. Conclusions: Treatment of lung cancer with chemotherapy during pregnancy should be considered on an individual basis with regard to the stage of the cancer and the maturity of the fetus. To our knowledge, the case presented here is the first report of a woman receiving chemotherapy for lung cancer while pregnant.
Reduced Fhit Expression Occurs in the Early Stage of Esophageal Tumorigenesis: No Correlation with p53 Expression and Apoptosis
Authors: Kitamura Atsushi , Yashima Kazuo , Okamoto Eiji , Andachi Hironobu , Hosoda Akihide , Kishimoto Yosuke , Shiota Goshi , Ito Hisao , Kaibara Nobuaki , Kawasaki Hironaka
Published: April 2003

The FHIT gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene involved in multiple tumors, including esophageal carcinoma. We analyzed Fhit expression using an immunohistochemical method in invasive carcinoma, carcinoma in situ (CIS) and dysplasia, in paraffin sections of 75 esophageal squamous cell carcinomas (ESCs) to further elucidate the role of Fhit protein in esophageal carcinogenesis. In addition, we also examined whether Fhit expression correlated with p53 expression and apoptosis. Compared to adjacent normal mucosa, significant loss or reduction of Fhit expression was noted in 67 of 75 (89.3%) invasive ESCs, in 13 of 19 (68.4%) CIS lesions, and in 10 of 23 (43.5%) dysplastic lesions. There was a progressive loss or reduction of Fhit expression with progressive increases in the severity of histopathological changes (p < 0.001). However, there was no association between Fhit expression and clinicopathological findings, including tumor stage, lymph node metastasis, or overall survival. Moreover, Fhit expression was not significantly associated with p53 expression and apoptosis. These results indicate that abnormal Fhit expression is a common event in the early stage of ESC development and may occur independently of p53 expression and apoptosis mechanisms.
A Phase I Trial of a 5-Day Schedule of Intravenous Topotecan and Etoposide in Previously Untreated Patients with Small-Cell Lung Cancer
Authors: O’Neill Penny , Clark Peter I. , Smith David , Marshall Ernest , Hannigan Kate , Ross Graham
Published: April 2003

A phase I dose-escalation study was undertaken to determine the maximum tolerated dose of the intravenous combination of topotecan and etoposide in previously untreated patients with small-cell lung cancer. Nineteen patients were treated with 30-min infusions of topotecan (0.5 mg/m2/day for cohort 1; 0.75 mg/m2/day for cohort 2) followed by 1-hour infusions of a fixed daily dose of etoposide (60 mg/m2/day) for 5 consecutive days every 3 weeks. Patient cohort 1 (n = 7) received a total of 41 courses of chemotherapy. Grade 4 neutropenia occurred after 17% of the courses of therapy, and there was 1 episode of dose-limiting toxicity in this patient cohort. In patient cohort 2 (n = 12), a total of 64 courses of chemotherapy were administered. Grade 3 or 4 neutropenia occurred following 41 and 37% of the courses of therapy, respectively. Grade 3 thrombocytopenia occurred following 19% of the courses of therapy, and there were 3 episodes of dose-limiting toxicity in this patient cohort. There were no toxic deaths, and all nonhematologic toxicity (except hair loss) was ≤ grade 2. No further dose escalation was performed because of the degree of myelosuppression seen in patient cohort 2. All 19 patients were evaluable for response. Eighteen (95%) patients responded (14 partial responses and 4 complete responses) and the median survival was 10 months. This 5-day schedule of intravenous topotecan and etoposide administered sequentially on the same day is well tolerated, and the preliminary response rates were high in patients with previously untreated small-cell lung cancer.
Pharmacological Evaluation of a New Timolol/Pilocarpine Formulation
Authors: Bucolo Claudio , Spadaro Angelo , Mangiafico Sebastiano
Published: April 2003

A new formulation (HYA) based on timolol hyaluronate and pilocarpine hyaluronate salts has been shown to improve the bioavailability of the drugs and to extend the duration of their action. Extent of the intraocular pressure lowering effect, duration of action and aqueous bioavailability of timolol and pilocarpine of HYA were compared with a commercial preparation. Ocular hypertension in the rabbit was induced by α-chymotrypsin or by water loading. The hypotensive effect of HYA treatment was significantly greater and longer than that observed in rabbit eyes treated with the commercial preparation both in the normotensive and in the hypertensive animals. Furthermore, we evaluated the miotic response; due to pilocarpine, normotensive rabbits showed a greater miotic response and an extended duration when the eyes were treated with HYA. The new formulation increased the aqueous availability of timolol and pilocarpine compared to the commercial preparation as determined by HPLC. The pharmacodynamic and pharmacokinetic profiles of HYA indicate an increase in efficacy and duration of action along with an increase in bioavailability of timolol and pilocarpine in comparison with the commercial preparation.
Intracameral Levels of Intravenously Injected Fluorescein, Cefmenoxime, and Chloramphenicol in the Prostaglandin E2-Administered Eyes of Albino Rabbits
Authors: Kato Tsuyoshi , Hiraki Shigeyoshi , Hayasaka Seiji
Published: April 2003

We evaluated the effects of inflammation and physicochemical nature of selected agents on the intracameral levels of intravenously injected drugs in albino rabbits. Transcorneal diffusion of prostaglandin E2 (10, 50 or 250 µg/ml) using a glass cylinder was used to produce inflammation of the anterior segment in the right eyes. As a control, a vehicle was applied to the left cornea. Immediately, 2, 5, or 11 h after prostaglandin E2 administration, a mixed solution of fluorescein, cefmenoxime, and chloramphenicol (50 mg each/kg body weight) was injected intravenously. One hour after injection of the drugs, the primary aqueous humor was withdrawn. The intracameral levels of protein and these drugs after prostaglandin E2 administration increased at 1 h in a dose-dependent manner. These levels then gradually decreased. One hour after prostaglandin E2 administration, the intracameral levels of protein and these drugs in the prostaglandin E2-administered eyes were significantly higher than those in the vehicle-administered eyes, except chloramphenicol after administration of 10 µg/ml prostaglandin E2. Our findings indicate that the intracameral levels of intravenously administered drugs are altered not only by the severity of inflammation but also by the properties of drugs.
Higher Glycation of βL- and βS-Crystallins in the Anterior Lens Cortex and Maximum Glycation of γ-Crystallins in the Bovine Lens Nucleus, Demonstrated by Frozen Sectioning, Isoelectric Focusing and Lectin Staining
Authors: Bours Johan , Ahrend Michael H.J. , Utikal Klaus J.
Published: April 2003

The aim of the current study was to demonstrate glycation of βL-, βS- and γ-crystallins in the young bovine lens. To establish which of the crystallins are glycated and where they are located in the lens, we carried out microsectioning of the lens, followed by isoelectric focusing (IEF). Four bovine lenses of 1.183 ± 0.070 years were frozen-sectioned into equator and 11 layers. Water-soluble crystallins were separated by IEF and stained: (1) with Coomassie brilliant blue for proteins; (2) with the lectin concanavalin A, followed by horseradish peroxidase and diaminobenzidine, for glycated proteins. Experiments were performed with crystallins and proteins in native form, in the absence of denaturants. The crystallins were separated by IEF into α-crystallins of high molecular weight (HM), αL-, βH-, βL-, βS- and γ-crystallins. In the lectin staining experiments, only HM, βL-, βS- and γ-crystallins were positive, whereas the αL- and βH-crystallins were negative. Contrary to the glycated γ-crystallins in the lens nucleus, the βS- and βL-crystallins were predominantly glycated in the anterior cortex and to a somewhat lower extent also in the posterior cortical regions. The degree of glycation (total densitometric readings of lectin-stained bands/Coomassie-blue-stained bands) is as follows: total γ-crystallins 2.44, βS-crystallins 0.77 and βL-crystallins 0.28. Though glycation in the bovine lens is very low, lectin staining is sufficiently sensitive to detect the various glycated crystallins. The degree of glycation of γ-crystallins was 3 times higher than that of βS-crystallins and 9 times higher than that of βL-crystallins.
The Effect of Glutathione upon Chaperone Activity of Alpha-Crystallin is Probably Mediated through Target Modulation
Authors: Pal Jaya , Bera Sibes , Ghosh Sudhir K.
Published: April 2003

We studied the effect of the presence of glutathione, both reduced (GSH) and oxidized (GSSG), on the chaperone activity of α-crystallin towards thermal aggregation of γ2-crystallin. Results showed that while GSH enhanced the chaperone activity of α-crystallin, GSSG appeared to diminish it to some extent. When, however, the effect of the presence of glutathione was studied in the absence of α-crystallin, the nature of their action was found to be almost similar to that observed in its presence. These results suggest that glutathiones probably modulate the target protein which ultimately influences the chaperone activity of α-crystallin.
Sialoglycoconjugates in Primary and Recurrent Mixed Tumors of Lacrimal Glands
Authors: Hayakawa Koichi , Ishikawa Makoto , Abe Tohru , Nakayama Ryuko , Yamaki Kunihiko , Sakuragi Shozo
Published: April 2003

We examined the activity of Griffonia simplicifolia II agglutinin (GS2) before and after neuraminidase treatment in 2 cases of primary benign mixed tumor (BMT) and a case of recurrent mixed tumor (MT). Histologically, each type of MT is comprised of epithelial and mesenchymal components. GS2, which showed no binding to either structural component in the primary BMT, was specifically bound to the mesenchymal component in the recurrent MT. After neuraminidase treatment, there was a marked increase in GS2-binding levels in the epithelial component of the primary BMT and in both components of the recurrent MT. These results might reveal a prominent sialylation in the recurrent MT.
Uveal Mast Cells Are Not Required for Rodent Uveitis
Authors: Smith Justine R. , Hart Prue H. , Coster Douglas J. , Williams Keryn A.
Published: April 2003

Uveal mast cells have previously been considered to be vital mediators of experimental uveitis. We extended the study of these cells to experimental melanin-induced uveitis (EMIU), a recently described clinically relevant model, and re-examined their role in endotoxin-induced uveitis (EIU) using genetically mast cell-depleted mice on a single background. EMIU was induced in Fischer 344 rats by immunisation with bovine ocular melanin (250 µg). Animals were killed immediately, and on days 1 and 3 of clinical disease. Numbers of uveal mast cells and the percentage of degranulated cells were counted in whole-mount preparations. There was no significant change in either measure across the selected time points. To induce EIU, normal and mast cell-depleted DBA/2 mice were injected with Escherichia coli lipopolysaccharide (400 µg). Cells infiltrating the eye 24 h after injection were quantified in 5 µm ocular cross-sections. Disease was not significantly reduced in the mast cell-depleted mutants. We conclude that uveal mast cells are not required for the development of EMIU or, in contrast to earlier work, EIU.
Human Immunoglobulin Preparations for Intravenous Use Prevent Endotoxin-Induced Uveitis in Rats
Authors: Obrador Esther , Peinado Enrique , de Kozak Yvonne , Ruiz-Moreno JoseM. , Alio JorgeL.
Published: April 2003

Objective: We analyzed the preventive effect of immunoglobulins for intravenous use (IVIgs) in endotoxin-induced uveitis (EIU), a disease related to tumor necrosis factor α (TNF-α) production. Materials and Methods: EIU was the experimental model in Lewis rats, injecting a systemic dose of 150 µg of lipopolysaccharide (LPS) into the rat’s footpad. Half of them were treated with 5 serial intravenous doses of 100 mg of IVIg during the 5 days prior to LPS injection. Eyes were repeatedly examined with a slitlamp, rats were killed and their eyes enucleated for histopathologic study at the 2nd, 16th and 24th hours. TNF-α serum levels were measured in aqueous humor at several time intervals by a bioassay using L-929 mouse fibroblasts. Aqueous humor proteins were detected by the Bradford method. Results: IVIg treatment prevented EIU development, treated animals showing a lower grade of ocular inflammation beyond the 2nd hour (Fisher test, p > 0.05). Inflammatory cell infiltration was significantly reduced in the iris, ciliary body and anterior chamber at a 24-hour interval (Wilcoxon test, p < 0.05). This protection was associated with lower levels of TNF-α in serum at all time intervals and in aqueous humor at 16 h (Student’s t test, p < 0.05), while differences were not significant between the samples of aqueous humor collected at 2 h. Protein exudate was not reduced in the treated group. Conclusions: Repeated IVIg injections could be useful in the preventive treatment of EIU probably mediated by a decrease in TNF-α release.
Variability in Digital Assessment of Cortical and Posterior Subcapsular Cataract
Authors: Robman L.D. , McCarty C.A. , Garrett S.K.M. , Maclean H. , McNeil J.J. , Taylor H.R.
Published: April 2003

To identify validity of the standardised Nidek EAS-1000 retroillumination image analysis, images of 450 consecutive patients were analysed for the standard 6.5 mm and for the maximal pupil size. The software allows for separation of cortical and posterior subcapsular opacities and defines threshold for cataract automatically at 12% below the brightest point of the histogram of pixel luminescence. The results were compared with clinical Wilmer cataract grading. Correlation between clinical and digital assessment was 0.48* for cortical opacities in maximal pupil size, 0.47* in 6.5 mm pupil size analyses, and 0.71* for posterior subcapsular opacities (*p < 0.001). In 24.6% of maximal pupil size analyses and in 11.7% of standard pupil size analyses standardisation revealed confounding features, such as other opacities of media, refractive shadows etc., that masqueraded as cataract and interfered with the cortical opacity measurements. Automatic standardized analysis has reduced many sources of observer variation (level of illumination, pupil size and threshold adjustment), but the revealed range of confounding opacities and artifacts still requires observer interpretation.
Immunostaining of the Estrogen Receptor in Conjunctival Primary Acquired Melanosis
Authors: Chowers Itay , Livni Nelly , Frucht-Pery Joseph , Pe’er Jacob
Published: April 2003

Conjunctival primary acquired melanosis (PAM) is a frequent precursor of conjunctival melanoma. Since there is indirect evidence that the conjunctiva is an estrogen-responsive tissue, and since it was suspected that estrogen has a role in the etiology of melanoma, we decided to evaluate whether PAM may be responsive to estrogen. Formalin-fixed, paraffin-embedded sections from 13 cases of PAM and 2 cases of conjunctival melanoma were immunostained with an estrogen-receptor (ER)-specific antibody. All lesions and the normal conjunctival tissue adjacent to the lesions were found to be ER negative. It is concluded that PAM and normal conjunctiva are not sensitive directly to estrogen. When considering previously reported data, it is conceivable that the normal conjunctiva, but not PAM, is indirectly affected by estrogen.
Vacuoles in the AcrysofTM Intraocular Lens as Factor of the Presence of Serum in Aqueous Humor
Authors: Dick H. Burkhard , Olson Randall J. , Augustin Albert J. , Schwenn Oliver , Magdowski Gerd , Pfeiffer Norbert
Published: April 2003

Objective: Acrysof™ (Alcon) foldable lenses (IOLs) have been shown to be highly biocompatible and exhibit a low incidence of posterior capsular opacification. However, minute vacuoles or ‘glistenings’ have been observed in some Acrysof IOLs. The clinical relevance of vacuole formation is presently unclear. To help clarify the influence of factors present under in vivo conditions on vacuole formation, the present experimental study examines the influence of aqueous humor components on the occurrence of vacuoles in Acrysof IOLs. Methods: A total of 12 sterile Acrysof IOLs (Alcon, MA60BM) were incubated at body temperature (37°C) for 3 or 6 months in anterior-chamber aqueous humor with or without human serum. The center portion was cut from two unconditioned, unhydrated, sterile control IOLs and the 12 conditioned IOLs and examined using light microscopy for vacuole formation. A third unconditioned, hydrated control IOL was examined using light and scanning electron microscopy. Measures: The incidence of vacuoles was quantified by two independent investigators using light microscopy. After hydration with balanced salt solution, the surface quality of a control IOL was examined using scanning electron microscopy. Results: The control IOLs exhibited no or very few vacuoles. Scanning electron microscopy revealed that the control IOLs had normal surface texture without any surface vacuoles. IOLs that had been conditioned in aqueous humor without serum exhibited no great increase in the number of vacuoles, whereas IOLs conditioned in aqueous humor with serum exhibited a greater number of vacuoles that increased over time. Conclusions: The number of vacuoles increases with incubation time in aqueous humor containing serum. The addition of serum increased the proportion of lipids and proteins in the solution, which also occurs with a breakdown in the blood-aqueous barrier. The results of the present study point to a physiological factor that may lead to vacuole formation in IOLs and may aid clinicians in identifying risk factors involved in the formation of vacuoles.
In vitro Susceptibilities to Topical Antibiotics of Bacteria Isolated from the Surface of Clinically Symptomatic Eyes
Authors: Egger Stefan F. , Ruckhofer Josef , Alzner Egon , Hell Markus , Hitzl Wolfgang , Huber-Spitzy Veronika , Grabner Günther
Published: April 2003

Background: The permanent change of resistance patterns of bacteria causing ocular infections makes repeat susceptibility testings against the most recent clinical isolates mandatory. The aim of the present study was to assess the in vitro susceptibility of ocular bacterial isolates of clinically symptomatic eyes admitted to the outpatient clinic of the eye department of a large central hospital to commonly used topical antibiotics. Methods: Ocular isolates (n = 454) were tested for their susceptibility to ofloxacin, ciprofloxacin, norfloxacin, gentamicin, tobramycin, meomycin, bacitracin, erythromycin, tetracycline and chloramphenicol. Results: All three tested fluoroquinolones were found to be very effective against gram-negative organisms but demonstrated some weakness against certain strains of gram-positive germs, in particular coagulase-negative staphylococci and Streptococcus viridans. These germs, however, were very susceptible to bacitracin and chloramphenicol. The relative overall in vitro efficacy was (in decreasing order): chloramphenicol, ciprofloxacin, ofloxacin, norfloxacin, bacitracin, tetracycline, neomycin, erythromycin, tobramycin and gentamicin. Conclusion: Chloramphenicol had the highest overall in vitro efficacy, but has potential lethal side effects. The fluoroquinolones were highly effective, especially being superior to the aminoglycosides tested, but no single antibiotic provided 100% coverage against all of the bacterial isolates that were tested.
Involvement of Oxygen Free Radicals in Experimental Retinal Ischemia and the Selective Vulnerability of Retinal Damage
Authors: Kuriyama Hiroshi , Waki Mitsunori , Nakagawa Masashi , Tsuda Motoyuki
Published: April 2003

Protective effects of CV-3611, a free radical scavenger, on retinal ischemic injury in the rat and on glutamate-induced cytotoxicity in a cell line were evaluated. Transient retinal ischemia was induced by raising intraocular pressure of rats to 110 mm Hg for 45 min, and the electroretinogram (ERG) was measured to evaluate retinal function. No ERG could be recorded immediately after reperfusion, and thereafter the ERG gradually recovered. Recovery of the a-wave latency and the amplitudes of the a and b waves in the CV-3611-treated (10 mg/kg, p.o.) group were significantly better than those in the control group up to 24 h after reperfusion. In both the control and CV-3611 group, the b wave showed better recovery than the a wave up to 6 h after reperfusion, while the relationship was reversed after 24-hour reperfusion. Glutamate (10 mM)-induced cytotoxicity in the N18-RE-105 cell, a neural retina-neuroblastoma hybridoma, was quantified by measuring lactate dehydrogenase. Three and 10 µM of CV-3611 significantly attenuated the glutamate-induced cytotoxicity in N18-RE-105 cells. Thus, the radical scavenger (CV-3611) promoted the recovery of retinal function after ischemia-reperfusion injury and ameliorated glutamate-induced cytotoxicity. These results suggest that oxygen free radicals play an important role in the early phase of retinal ischemic injury. Moreover, differential recovery processes of the a and b waves after ischemia suggest that the selective vulnerability of the retina to ischemia could change functionally during the period of reperfusion.
Light Scattering in Normal and Cataractous Lenses of Farmed Atlantic Salmon (Salmo salar): A Slit Lamp and Scheimpflug Photographic Study
Authors: Wegener A. , Laser H. , Ahrend M.H.J. , Breck O. , Bjerkås E. , Glöckner C. , Midtlyng P.J. , Breipohl W.
Published: April 2003

To investigate normal light scattering and cataract formation, the anterior eye segments of farmed Atlantic salmon (Salmo salar) reared in fresh water and sea water were documented in vivo for the first time with a Topcon SL-45 Scheimpflug camera. A total of 40 fish from the fresh-water-rearing period, obtained from 2 groups of identical age but showing a different growth rate, and 24 fish from the sea-water-rearing period, sampled from 2 groups with identical age but being fed different food brands, were included in this study. The fish were anaesthetized before examination. Due to the naturally wide pupil, no mydriatic compound was applied. All fish were removed from the water for photography, which was performed for each eye in 0° = vertical slit position. Images were recorded on Kodak Tmax 400 black-and-white film. Microdensitometric image analysis of all negatives was performed using a Joyce-Loebl online microdensitometer. In spite of the virtual absence of an anterior chamber gap between cornea and lens and very little light scattering in the normal fish lens, a small number of distinct layers could be reproducibly identified in the lens. While there was little abnormal light scattering which could point to cataract development in young fish from the fresh water period, the evaluation of the lenses from the 2 sea water groups showed the presence of specific forms of cataract especially in the cortical and supranuclear layers. There were significant differences between the groups fed different food brands at the sea water site. In conclusion, Scheimpflug photography proved to be applicable to eye research in fish in vivo. It is suggested that this method should be employed for reproducible documentation as an extension to slit lamp monitoring in experimental research to reveal causative factors for cataracts in farmed fish.
Effect of Pneumatic Suction Ring Placement on Intraocular Pressure in Cats
Authors: Li Bing
Published: April 2003

Purpose: To determine the effect of placing a pneumatic suction ring on intraocular pressure (IOP) in the cat and to design an improved method to generate a stable elevation of IOP. Methods: A pneumatic suction ring was applied to the eye in cats while the IOP was monitored. Three groups of animals (10 per group) were used. A vacuum pressure of 450 mbar was applied in one step to eyes of group 1 (anesthetized) and to group 2 (euthanized) cats. In group 3 (anesthetized) cats, an initial vacuum pressure of 250 mbar was applied, followed by a vacuum of slowly increasing pressure at a rate of 5 mbar/min for a total of 40 min to 450 mbar. Results: After the one-step application of a vacuum (450 mbar) to the eyes of anesthetized cats (group 1), IOP peaked within the first minute from a basal value of 25 ± 2 mm Hg (mean ± SD) to 90 ± 7 mm Hg. It then rapidly decreased to 69 ± 2 mm Hg 5 min later and continued to decrease to 39 ± 4 mm Hg 40 min later. This sharp peak and decline of IOP were also observed in eyes of euthanized cats (group 2). The basal IOP of these eyes was 8 ± 1 mm Hg. It rose to 18 ± 2 mm Hg immediately after the application of vacuum pressure (450 mbar) and returned to the basal level 5 min later. In contrast, the eyes of group 3 receiving an initial vacuum of 250 mbar followed by a 5 mbar/min vacuum increment exhibited a rapid increase in IOP and a very stable plateau (mean IOP = 62–68 mm Hg), lasting the whole study period (40 min). Conclusion: IOP after a one-step application of a vacuum via a pneumatic suction ring is self-adjusting and declines rapidly over time. This decline in IOP can be overcome by a supplementary increment in vacuum pressure.
Proposal of Standardization on Screening Tests for Detection of Distant Metastases from Head and Neck Cancer
Authors: Johnson Jonas T.
Published: April 2003

A standardized approach to screening for distant metastases must be flexible. This reflects the fact that the issues involved have not been adequately studied to allow evidence-based recommendations. Effective and responsible application of screening for distant metastasis would improve our ability to council patients regarding important therapeutic decisions. It would also have important consequences on healthcare economics. Screening recommendations should reflect the stage of the primary tumor and the histologic cell type because these two parameters most clearly correlate with the risk for distant metastases. The most commonly encountered distant metastases are pulmonary. The most sensitive validated screening technique is just computed tomography (CT). Advanced technologies such as simultaneous positron emission tomography/CT may replace these prior technologies in the near future. Recommendations for routine screening following curative treatment are subjective at this time. Careful history and physical examination remains the basis for the follow-up evaluation. The sensitivity and cost effectiveness of imaging studies in this setting remains unstudied and contentious.
Treatment of Snorers with a Volatile Oil
Authors: Ulfberg Jan , Nyström Birgitta
Published: April 2003

Snoring is a significant problem both for the patient and for the bed partner. Seventy-two male and female heavy snorers and their bed partners participated in a double-blinded, placebo-controlled study on the effects of a volatile oil administered by gargling. The patients were diagnosed as heavy snorers after they underwent overnight polysomnography showing that their apnea indexes were below 5, thus sleep apnea patients were not included in the study. The participants and their partners filled out evaluations concerning snoring intensity, mouth dryness, nasal stuffiness and the Epworth Sleepiness Scale prior to and after using the volatile oil or placebo for 14 consecutive nights. There were no statistically significant decreases in snoring as graded by the bed partner or in mouth dryness, nasal stuffiness, or the Epworth Sleepiness Scale scores graded by the patients who were randomized to use the volatile oil. The results of this study indicate that this volatile oil is not an effective treatment in patients presenting with symptoms of snoring.
Point Mutation of the Mitochondrial Genome in Japanese Deaf-Mutism
Authors: Oshima Takeshi , Kudo Takayuki , Ikeda Katsuhisa
Published: April 2003

Recently, a number of hearing-impaired individuals with mitochondrial genome (mtDNA) mutations have been reported, and it is well known that the mtDNA mutations are responsible for the hearing disorder. We have demonstrated that the mtDNA mutation A3243G is responsible for adult-onset sensorineural hearing loss (SNHL). At the same time, a case in which SNHL occurred within 2 years from birth has been reported. The mtDNA mutations may be possible causes of prelingual deafness. In the present study, the mtDNA fragments from the deaf-mute persons were amplified by polymerase chain reaction, followed by a restriction enzyme fragment length polymorphism method and direct sequencing. We failed to find A3243G involvement in 46 deaf-mutes but found that 8.7% of them had A1555G which is an important cause of prelingual deafness, no less than autosomal recessive inheritance, in Japan.
Recovering DNA and Optimizing PCR Conditions from Microdissected Formalin-Fixed and Paraffin-Embedded Materials
Authors: Ren Zhi-Ping , Sällström Jan , Sundström Christer , Nistér Monica , Olsson Yngve
Published: April 2003

Microdissection is a powerful technique in molecular pathology and genetic investigations. To detect genetic alterations such as gene mutation or deletion from tumor specimen, the purity of target cells is extremely critical. Unwanted cell contamination will dramatically dilute the detectable level of the abnormality. The major obstacle in clinical research is to obtain sufficient and qualified DNA from a small amount of formalin-fixed and paraffin-embedded materials. We have successfully modified our previous protocols and overcome the difficulties of recovery of DNA. After these modifications, almost every single formalin-fixed and paraffin-embedded specimen has been successfully amplified in the required DNA region.
De novo Spinal Teratoma after Treatment of an Intracranial Germ Cell Tumor
Authors: Tohma Yasuo , Kaneko Takuro , Kita Daisuke , Iwato Masayuki , Hayashi Yutaka , Tachibana Osamu , Hasegawa Mitsuhiro , Yamashita Junkoh
Published: April 2003

The authors report an extremely rare case of de novo spinal teratoma after treatment for intracranial germ cell tumor. A 17-year-old male developed pain of bilateral lower extremities and urinary retention 18 months after complete remission of intracranial mixed germ cell tumor. Magnetic resonance imaging revealed a huge spinal tumor associated with spina bifida occulta. Total resection was performed, and histogenetical findings led to the diagnosis of a mature teratoma with normal p16 gene, whereas analysis of intracranial tumor showed p16 deletion. The spinal anomaly and genetic analysis strongly suggest that the spinal teratoma was a de novo tumor rather than a metastasis or dissemination of the original intracranial germ cell tumor.
Neurocutaneous Melanosis Associated with Dandy-Walker Malformation
Authors: Berker Mustafa , Oruckaptan H. Hakan , Oge H. Kamil , Benli Kemal
Published: April 2003

Neurocutaneous melanosis is a rare dysmorphogenesis associated with single or multiple giant pigmented cutaneous nevi and diffuse involvement of the leptomeninges anywhere in the central nervous system (CNS). It is interesting that almost 8–10% of patients had associated Dandy-Walker malformation in the literature, suggesting a common origin of the developmental abnormalities. In this article, we present a 2-year-old patient with neurocutaneous melanosis associated with Dandy-Walker malformation. We reviewed the literature and discuss the pathogenesis based on the preferred hypotheses so far.
An Occipital Encephalocystocele Involving Both Sides of the Lateral Ventricles
Authors: Yamada Kazumichi , Miura Masaki , Matsumoto Jun , Uchino Takako , Kondo Yuichi , Ushio Yukitaka
Published: April 2003

We reported a rare case of an occipital encephalocystocele linked by bilateral posterior horns of the lateral ventricles. The subject was a newborn girl with a large occipital cephalocele (6 × 9 cm in diameter) covered with alopetic skin. Cerebrospinal fluid leakage was not observed. The fontanel was soft, but a characteristic flat forehead was noted. Neither neurological deficits nor cardiopulmonary dysfunctions were evident at birth. Magnetic resonance images revealed that the sac contained the occipital lobes and that the cavity was linked by bilateral posterior horns. Agenesis of the corpus callosum and dysgenesis of the falx cerebri were associated. Fifteen days after birth, the cephalocele was removed surgically. Cutting sections revealed that the cephalocele contained enlarged bilateral posterior horns and cerebral hemispheres. The postoperative course was uncomplicated by hydrocephalus or infection, and the patient was discharged without any neurological deficit 22 days after surgery. Her milestone was survival; and at present 12 months after surgery, she is alive with moderate developmental retardation.
Parietal Pseudofracture and Spontaneous Intracranial Hemorrhage Suggesting Nonaccidental Trauma: Report of 2 Cases
Authors: Fenton L.Z. , Sirotnak A.P. , Handler M.H.
Published: April 2003

Massive intracranial hemorrhage, no history of trauma and radiographic findings that were initially interpreted as linear parietal fractures raised the possibility of nonaccidental trauma in 2 infants. Both had severe coagulopathy, 1 due to hemorrhagic disease of the newborn (vitamin K deficiency) and the other due to disseminated herpes simplex virus infection. Both infants died. At autopsy, the parietal bone abnormalities were not fractures, but proved to be an anomalous suture in 1 and a connective tissue fissure in the other.
Spina Bifida Outcome: A 25-Year Prospective
Authors: Bowman Robin M. , McLone David G. , Grant John A. , Tomita Tadanori , Ito Joy A.
Published: April 2003

Background: Open spina bifida is the most complex congenital abnormality compatible with long-term survival. This report outlines the 20- to 25-year outcome for our original cohort of patients with a myelomeningocele treated in a nonselective, prospective manner. Methods: Of the initial 118 children, 71 patients were available for our most recent review. Nineteen patients have been lost to follow-up and 28 patients have died. Data were collected on: motor level, shunt status, education/employment, seizure history, mobility, bladder/bowel continence, tethered cord, scoliosis, latex allergy, posterior cervical decompression, tracheostomy and/or gastrostomy tube. Results: Mortality (24%) continues to climb into young adulthood. Eighty-six percent of the cohort have cerebrospinal fluid diversion, with 95% having undergone at least one shunt revision. Thirty-two percent have undergone a tethered cord release, with 97% having an improvement or stabilization in their preoperative symptoms. Forty-nine percent have scoliosis, with 43% eventually requiring a spinal fusion. Sixteen patients (23%) have had at least one seizure. Eighty-five percent are attending or have graduated from high school and/or college. More than 80% of young adults have social bladder continence. Approximately 1/3 of patients are allergic to latex, with 6 patients having experienced a life-threatening reaction. Conclusion: At least 75% of children born with a myelomeningocele can be expected to reach their early adult years. Late deterioration is common. One of the greatest challenges in medicine today is establishing a network of care for these adults with spina bifida.
Successful Use of Rib Grafts for Cranioplasty in Children
Authors: Taggard Derek A. , Menezes Arnold H.
Published: April 2003

Numerous materials are available for use in cranioplasty including bone, plastics and metals. Rib grafts as a construct for cranial reconstruction offer several advantages: autologous bone source, a formable platform, low infection, regeneration at the donor site and high fusion rates. Criticism of rib graft cranioplasty includes scarring and pain at the donor site, irregular contour at the graft site and graft reabsorption. Since 1988, we have performed rib autograft cranioplasty on 13 patients. Seven females and 6 males combined for an average age of 6 years (11 months to 20 years) at the time of surgery. The mean follow-up from surgery is 27 months (2–48 months), with 11 subjects having at least 12 months. The commonest reasons for cranial reconstruction were: post-traumatic calvarial defect (n = 4), defect from previous craniotomy (n = 3), ‘growing’ skull fracture (n = 2), and defect from previous encephalocele closure (n = 2). Mean defect size was 41 cm2 (8–144 cm2) and average number of ribs harvested was 1.75 (1–3). Simple rib cranioplasty had a mean time in the operating room of 6 h and 30 min. No donor site complications were noted (pneumothorax, significant post-operative pain) and no post-operative infections were encountered. Excellent cranial contour was achieved in each of the 11 patients followed for a minimum of 12 months. One subject required staged reconstructive procedures owing to the size of the defect.