bluuebunny/crossref_metadata_2025 huggingface dataset:
Occlusion Therapy for the Treatment of Amblyopia: Letting the Parents Decide
Authors: Tripathi Ajay , O’Donnell Niall P. , Holden Roger , Kaye Lesley , Kaye Stephen B.
Published: April 2003

Background: Compliance with prescribed occlusion therapy is a significant problem in the treatment of amblyopia. Parental preference for a particular type of occlusion treatment has not been previously addressed. Unless parental views are taken into account when planning therapy, compliance may be poor and treatment may fail. Subjects and Methods: Parents of children with strabismic and/or anisometropic amblyopia who were due to start or had already had occlusion treatment were included in this study. Group A comprised parents of children who had no previous experience of occlusion, and group B comprised parents of children who had previous experience of occlusion therapy. Parental preferences regarding occlusion therapy were investigated by way of a questionnaire, in which they were asked whether they would prefer part-day/full-week occlusion or all-day/part-week occlusion so that the total number of hours of occlusion per week was the same. Results: One hundred parents completed the questionnaire, 47 from group A and 53 from group B. A significant number of parents in group A (95.3%) who had no previous experience with occlusion preferred part-day/full-week occlusion (p < 0.001), whereas there was no such preference among parents who had experience with occlusion, that is only 54.3% of parents in group B showed a preference for part-day/full-week occlusion (p = 0.1). The reasons given by the parents for their preferences varied but were in keeping with their lifestyles so that the type of occlusion regimen chosen by the parents was in accordance with the reasons given for their choice. Conclusion: Parental preferences should be considered when occlusion therapy is planned if compliance is to be improved. For maintenance occlusion, it would be reasonable to prescribe the number of hours of occlusion required per week and allow parents the responsibility to implement the pattern of occlusion according to their circumstances – the implied restriction ensuring that the number of hours of occlusion per week is met. Although parents appeared to have preconceived ideas before the commencement of treatment, their preferences changed once treatment had begun.
Efficacy of Latanoprost Additive Therapy on Uncontrolled Glaucoma
Authors: Bayer Atilla , Tas Ahmet , Sobacı Gungor , Henderer Jeffrey D.
Published: April 2003

Purpose: To assess the efficacy of latanoprost as additive therapy in patients with open-angle glaucoma and an intraocular pressure (IOP) deemed to be too high on maximum tolerated medical therapy. Study Design: Prospective case series. Methods: Consecutive patients with open-angle glaucoma, presenting to the Gulhane Military Medical Hospital Ophthalmology Clinic from May 1999 to September 2000 were enrolled. The effect of latanoprost on IOP was followed during a period of 12 months. The criterion for success was defined as having an IOP reduction of at least 20% from baseline or a final IOP of less than 22 mm Hg. Several clinical pretreatment variables (age, gender, ocular laterality, type of glaucoma, number of antiglaucomatous medications at study entry, pretreatment IOP) were analyzed for a significant effect on the efficacy of latanoprost additive therapy. Main Outcome Measure: IOP. Results: Sixty-five eyes of 35 patients were included. The mean baseline IOP ± SD was 23.3 ± 2.0 mm Hg. Two patients (5.71%) developed ocular allergy in the first month requiring cessation of latanoprost. In the remaining 61 eyes of 33 patients, IOP was significantly reduced compared with baseline measurements with a mean IOP reduction of 6.1 ± 1.8 (26.1%), 6.0 ± 2.2 (25.3%) and 5.5 ± 2.4 (23.2%) mm Hg at the 1-, 3- and 6-month follow-up controls, respectively (p < 0.001). Successful outcome was obtained in 50 (76.9%), 46 (70.7%) and 38 (58.4%) of 65 eyes at the 1-, 3- and 6-month visits, respectively. During the period from 6 to 12 months, 28 eyes underwent either a combined procedure (cataract extraction + intraocular lens implantation + trabeculectomy; 8 eyes) or only trabeculectomy (20 eyes) because of uncontrolled IOP; 4 eyes underwent the combined procedure because of visually significant cataract, and 8 eyes were lost to follow-up. Sixteen out of 21 eyes followed for more than 12 months with the same medications continued to have a successful outcome, and the mean IOP of 18.8 ± 3.7 mm Hg was significantly different from baseline (p < 0.001). None of the pretreatment variables was a significant prognostic factor for failure of latanoprost additive therapy. Conclusion: This study supports the use of latanoprost additive therapy in patients with elevated IOP already receiving maximum-tolerated medical therapy.
Human Cerebellar Activation in Relation to Saccadic Eye Movements: A Functional Magnetic Resonance Imaging Study
Authors: Hayakawa Yuuki , Nakajima Takashi , Takagi Mineo , Fukuhara Nobuyoshi , Abe Haruki
Published: April 2003

Purpose: The functional organization of the human cerebellum involved in saccadic eye movements was investigated using functional magnetic resonance imaging (fMRI). Methods: The subjects were 7 normal volunteers aged 18–34 years. Visual stimuli were back-projected onto a screen placed at the subjects’ feet. The stimulation period of 30 s consisted of a saccade target jumping back and forth horizontally by 20° once per second. The control period of 30 s consisted of a fixed target. The stimulation and control periods were alternated 10 times during the presentation. Functional images were collected with a 1.5-tesla clinical MRI scanner. The significance of activation was determined by Statistical Parametric Mapping (SPM 99) at a threshold of p < 0.001 (uncorrected), and significantly activated areas were superimposed on the T1-weighted images. Results: Significantly activated areas related to visually guided saccades were observed in the cerebellar vermis (declive and folium), in the bilateral cerebellar hemispheres (mainly the superior semilunar lobule) of the cerebellum, in the frontal eye field, in the supplementary eye field and in parts of the parietal lobule of the cerebrum. Conclusion: Our results suggest that the cerebellar posterior vermis and bilateral hemispheres are related to saccades in humans. These results are consistent with neurophysiological data obtained in primates.
Does Photorefractive Keratectomy Alter the Effect of Topical Medications?
Authors: Nemet Arie , Morad Yair
Published: April 2003

Introduction: The influence of photorefractive keratectomy (PRK) on drug penetration into the eye is not yet established, as this procedure may alter the barrier function of the cornea as well as the blood ocular barrier. Pupillary response to topical tropicamide depends on its penetration into the anterior chamber. The purpose of this study was to examine the influence of PRK on pupillary response to topical tropicamide, and hence to evaluate whether PRK alters drug penetration into the eye. Methods: Pupillary diameter was measured using infrared pupillometer at 0, 15 and 30 min after instillation of 0.1% tropicamide to both eyes of 28 patients 4 weeks after PRK in one eye. The untreated eye served as control. Results: Pupillary diameter before and 30 min after dilation was 7.4 ± 1.2 and 8.0 ± 1.0 mm in the treated eyes and 7.5 ± 1.2 and 8.1 ± 1.0 mm in the untreated eyes, respectively (p = 0.45). Percentage of pupillary dilation (Δ pupillary diameter/pupillary diameter at 0 min ×100) was also similar in treated and untreated eyes for the entire study group (12.5 and 10.5%, respectively, p = 0.17). A trend for greater dilation was seen in patients with myopia above 6 diopters (13.7 and 10.5% in treated and untreated eyes, respectively, p = 0.11) and cornea thinner than 540 µm (14.2 and 10.1% in treated and untreated eyes, respectively, p = 0.1). Discussion: Our results confirm animal and human studies that found restoration of the ocular drug barrier at 4 weeks following PRK. The trend for greater penetration in patients with high myopia and thin corneas warrants further study on a larger cohort of this subgroup.
The Effect of Intrauterine Myelomeningocele Repair on the Incidence of Shunt-Dependent Hydrocephalus
Authors: Tulipan Noel , Sutton Leslie N. , Bruner Joseph P. , Cohen Brian M. , Johnson Mark , Adzick N. Scott
Published: April 2003

Background: Intrauterine myelomeningocele repair (IUMR) was first successfully performed in 1997. Preliminary reports suggest that this procedure reduces the incidence of shunt-dependent hydrocephalus when compared to conventional postnatal therapy. However, the existing cohort of IUMR patients has not yet been systematically compared to a comparable group of conventionally treated controls. Methods: Patients 1 year old or greater who had undergone IUMR at either Vanderbilt University or the Children’s Hospital of Philadelphia (CHOP) were compared to a group of conventionally treated historical controls treated and followed at CHOP. In order to measure any differences between the groups, patients were stratified according to the level of the myelomeningocele lesion and the gestational age at the time of IUMR. Results: One hundred and four IUMR patients were compared to 189 conventionally treated controls. IUMR resulted in statistically significant reductions in the incidence of shunt-dependent hydrocephalus at both lumbar and sacral lesion levels. When lumbar lesion levels were further stratified, from L1 to L5, it appeared that the benefit of IUMR was statistically significant only at levels below L2. Other factors with a significant impact on hydrocephalus were estimated gestational age and ventricular size at the time of surgery. In particular, statistically significant differences compared to controls were seen in the younger (≤25 weeks) group but not in the older (>25 weeks) group. Conclusions: IUMR appears to substantially reduce the incidence of shunt-dependent hydrocephalus when compared to conventional treatment even when lesion level is taken into account. Patients with lesions above L3 may not share in this benefit. IUMR cannot be justified in fetuses older than 25 weeks of gestation. Additional improvements might be obtained by further reducing the average age at which fetuses are operated upon. It remains to be determined whether this benefit outweighs the potential risks of intrauterine surgery.
Magnetic Resonance Imaging and High-Resolution Computed Tomography in the Otospongiotic Phase of Otosclerosis
Authors: Stimmer H. , Arnold W. , Schwaiger M. , Laubenbacher C.
Published: April 2003

Otosclerosis very often leads to severe hearing loss in a chronic progressive manner. In the first phase of the disease, otospongiosis causes an inflammatory osteolytic process in the osseous labyrinthine capsule. In the cases reported here, this osteolytic process was pronounced in the osseous capsule of the cochlea. High-resolution CT and MRI showed the precise localization and stage of this inflammatory-osteolytic process in the petrous bone, while scintigraphy confirmed the diagnosis.
Results of Singular Neurectomy in the Posterior Ampullary Recess
Authors: Gacek Richard R. , Gacek Mark R.
Published: April 2003

Objective: To determine the effect on hearing and balance symptoms following singular neurectomy (SN) for benign paroxysmal positional vertigo (BPPV) in the ampullary recess of the posterior semicircular canal. Research Design: The charts of 242 patients with chronic disabling BPPV who were treated with SN over a 29-year period (1972–2001) were reviewed. The results on relief of BPPV and hearing function were recorded. A subset of 16 patients where the posterior ampullary recess was entered to expose the SN is described in detail with regard to an effect on hearing and balance. Results: A total of 252 SN were performed in 242 patients. Ten patients underwent bilateral SN sequentially; the remaining 232 patients had unilateral SN. The ages of the patients ranged from 21 to 86 years, with a mean at 57 years. The female:male ratio was 174:68. Complete relief of BPPV was achieved in 244 patients (96.8%), incomplete relief in 3 (1%), and no relief in 5 (2%). Sensorineural hearing loss (SNHL) occurred in 9 patients (3.7%). A subset of 16 patients in whom the ampullary recess was opened during SN ranged in age from 21 to 79 years, with a mean at 56 years. The female:male ratio was 12:4, with right and left sides divided almost equally. Relief of BPPV was achieved in all 16 patients with no loss of hearing function. Five patients complained of a fistula response postoperatively (31%). The fistula response resolved by 6 months postoperatively in all 5 patients. Conclusions: SN is effective in relief of BPPV with little risk of SNHL (3.7%). The risk of SNHL is not increased when the posterior ampullary recess must be entered in order to transect the singular nerve. A positive fistula response may be present temporarily in almost one third of these patients.
Olfactory Neuroblastoma
Authors: Iliades Theofilos , Printza Athanasia , Eleftheriades Nikolaos , Georgios Kekes , Psifidis Anestis , Thomas Zaramboukas
Published: April 2003

Olfactory neuroblastoma is a rare malignant tumour, usually diagnosed at advanced stages. We studied 3 patients who were treated at our Institute between 1991 and 1999. One patient presented with a stage A and 2 with a stage B tumour. One patient presented with coma due to inappropriate secretion of antidiuretic hormone associated with a stage B tumour. All 3 patients were treated with complete surgical resection via a lateral rhinotomy approach and postoperative radiotherapy. There was no involvement of the cribriform plate. One patient developed a metachronous regional metastasis and was treated with neck dissection and radiotherapy. All 3 patients are free from recurrence with a follow-up period of 9 years, 18 months and 1 year, respectively. Combination therapy is the cornerstone of treatment for olfactory neuroblastoma. Complete surgical resection is the most important prognostic factor and can be accomplished via lateral rhinotomy for early stage tumours.
The Suprameatal Approach in Cochlear Implant Surgery: Our Experience with 80 Patients
Authors: Kronenberg Jona , Migirov Lela , Baumgartner Wolf Dieter
Published: April 2003

The suprameatal approach (SMA) was first performed in 1999. It was developed for cochlear implantation as an alternative to the classic technique of transmastoid posterior tympanotomy approach. In the course of SMA the middle ear is exposed from the external auditory canal and the electrodes are inserted into the cochlea through a suprameatal tunnel bypassing the mastoid cavity. The goal of developing the SMA was to simplify the surgical technique, shorten the duration of surgery, enable wide exposure of the middle ear during the procedure, and avoid possible damage to the facial nerve and chorda tympani. We report here the results of 80 patients who were operated on using the SMA technique.
Veria Operation Updated
Authors: Kiratzidis Trifon , Arnold Wolfgang , Iliades Theophilos
Published: April 2003

The Veria operation is a non-mastoidectomy technique for cochlear implantation. It uses the transcanal approach to the middle ear and the cochlea. The steps of the procedure are: (1) endaural approach, that offers a wide accessibility to the middle ear structures; (2) inspection of the middle ear anatomy; (3) straightening of the postero-superior bony canal wall, which is usually concave; (4) performing the cochleostomy through the outer ear canal; (5) drilling of the suprameatal hollow, which is used for the accommodation of the electrode excess; (6) drilling of the trans-wall direct tunnel, which is the pathway for the active electrode; (7) alignment of the direct tunnel to the cochleostomy; (8) extension of the incision and preparing of the flaps; (9) creating of the bed and fixing the device; (10) insertion of the electrodes; (11) manipulating the excess of the active electrode, and (12) closing. For this technique, two special instruments have been developed: a special perforator used for the drilling of the direct tunnel for the active electrode, making it completely safe, and a safety electrode forceps used to manipulate the active electrode during insertion. The direct tunnel can be enlarged superiorly permitting insertion of two electrodes, in cases where a double electrode array implant has to be used. The method is an efficient tool for handling all cochlear implant cases, including difficult ones such as revision cases, malformations, cochlear ossifications and poor mastoid development. It is safe without complications in over a hundred cases and easy to learn.
Effect of Centrally Administered Insulin on Gonadotropin-Releasing Hormone Neuron Activity and Luteinizing Hormone Surge in the Diabetic Female Rat
Authors: Kovacs Peter , Parlow Albert F. , Karkanias George B.
Published: April 2003

Diabetic female rats have decreased ovulation, sexual behavior, and luteinizing hormone (LH) surges. Peripheral insulin treatment restores the phenotype to normal. We administered central insulin and analyzed serum LH during the time of the LH surge in diabetic and non-diabetic animals to determine if central insulin was sufficient to normalize the phenotype. We assessed the activity and number of hypothalamic gonadotropin-releasing hormone (GnRH) neurons by double label immunocytochemistry for c-Fos and GnRH to determine if decreased GnRH neuron activity or number could account for the diabetes-induced deficits in neuroendocrine function. All animals were ovariectomized and given estradiol and progesterone. Diabetic and control animals were given either intracerebroventricular (ICV) insulin or saline. In experiment I, serial blood collection was performed. In experiment II, animals were sacrificed and their brains were processed for immunocytochemistry during the presumed LH surge. Experiment I showed that diabetic, saline-treated animals were unable to trigger an LH surge. Central insulin restored LH production to control levels. Experiment II revealed similar numbers and activation of GnRH neurons in all four groups. Therefore, the diabetes-induced loss of the LH surge cannot be explained simply by a reduction of GnRH-expressing neurons or by a decrease in GnRH neuronal activity.
Medical Ethics: A Rational Approach to Patient Management
Authors: Livadas Gerry
Published: April 2003

Physicians make their decisions based upon scientific evidence with their first consideration being the Hippocratic axiom ‘not to do harm’. In practice, a number of non-medical issues influence this process and generate conflicting judgments. We analyze these issues that form the context of medical ethics which is perceived as a subject wider than morality. It is also a religious, social, political, economic, legal and cultural issue. Therefore, the patient, physician and other professionals play important roles in the decision-making. The final decision is not a decision based on medical textbooks, but is rational in that it is based on reason for the benefit of the individual.
Arcus tendineus levator ani Tear Causing Pelvic Hematoma after Tension-Free Vaginal Tape Insertion
Authors: Chan Lin Wai , Pang Man Wah , Yip Shing-Kai
Published: April 2003

Although vaginal tamponade is usually sufficient for hemostasis, it is not useful if a pelvic hematoma occurs. Here, we report the unusual case of a large pelvic hematoma necessitating laparotomy for hemostasis due to a tear of the arcus tendineus levator ani after insertion of a tension-free vaginal tape.
Actinomycotic Tubo-Ovarian Abscess Mimicking Pelvic Malignancy
Authors: Güngör Tayfun , Parlakyiğit Emel Ebru , Dumanli Hüseyin
Published: April 2003

A 39-year-old multipara was admitted to hospital with lower abdominal pain. She had used an intrauterine device (IUD) for 10 years. Three years ago, her tubes were ligated. Ultrasound examination revealed a 9.5 × 6 cm multiloculated cystic mass in the right part of her lower abdomen. CA-125 was also found to be increased. Since ovarian malignancy was suspected, laparotomy was performed. Pathologically, an actinomycotic tubo-ovarian abscess with sulfur granules was disclosed.
Dysgerminoma in a Patient with a Tumor of the Neck
Authors: Isaka Keiichi , Akaeda Tomoyoshi , Itoh Hitoshi , Hori Kazuhiro , Yudate Tamaki , Nagata Junko , Suzuki Yasunobu , Takayama Masaomi
Published: April 2003

The evolution of therapy for malignant ovarian germ cell tumors is one of the true success stories in oncology. Treatment outcome has improved greatly thanks to cisplatin-based combination chemotherapy. According to the well-established treatment guidelines for advanced cases, we treated a case of stage IV undifferentiated germ cell tumor in which we were able to preserve the patient’s fertility. We concluded that the PEP regimen is an effective treatment for the patient with metastatic germ cell tumor.
Ethanol Reduces Cardiac Myocyte Function through Activation of the Nitric Oxide-Cyclic GMP Pathway
Authors: Weiss Harvey R. , Haim Todd , Zhang Qihang , Vaks Yakir
Published: April 2003

We tested the hypothesis that low-dose ethanol would reduce cardiac myocyte function through increased production in the nitric oxide/cyclic GMP signal transduction pathway, rather than reduced degradation. Ventricular myocytes were isolated from the hearts of 9 rabbits. Myocyte function was studied using a video-edge detector and cyclic GMP levels were measured by radioimmunoassay. Cells were administered 5 and 10 mmol/l ethanol alone or after 10–6 mol/l NG-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor), 10–6 mol/l 1H-[1,2,4]oxadiazolo[4,3a]quinoxalin-1-one (ODQ, soluble guanylyl cyclase inhibitor) or 10–5 mol/l zaprinast (cyclic GMP phosphodiesterase inhibitor). Ethanol (10 mmol/l) significantly decreased percent shortening from 10.0 ± 0.9 to 6.0 ± 0.2%. Similar decrements occurred in the maximum rate of shortening and relaxation. After L-NAME or ODQ, the decrements in percent shortening, maximum rate of shortening and relaxation caused by ethanol were not significant. After zaprinast, ethanol significantly decreased the maximum rate of shortening and relaxation and percent shortening to 4.3 ± 0.5. Ethanol (10 mmol/l) significantly increased cyclic GMP from 403 ± 121 to 529 ± 128 fmol/105 myocytes. Both L-NAME and ODQ lowered cyclic GMP, and ethanol did not affect cyclic GMP after either. Zaprinast raised cyclic GMP, as did its combination with 10 mmol/l ethanol (653 ± 120). Thus, ethanol both reduced myocyte function and increased cyclic GMP. Blocking nitric oxide production or guanylyl cyclase activity prevent these effects of ethanol, while blocking cyclic GMP degradation did not. This suggests that ethanol acts as a nitric oxide stimulator in ventricular myocytes leading to reduced function and increased cyclic GMP.
Mechanism of the Protective Effect of Heteropolyoxotungstate against Herpes Simplex Virus Type 2
Authors: Dan Katsuaki , Miyashita Kiichi , Seto Yoshiko , Fujita Haruhisa , Yamase Toshihiro
Published: April 2003

The effects of heteropolyoxotungstate (K7[PTi2W10O40]· 6H2O; PM-19) on the replication of herpes simplex virus type 2 (HSV-2) were examined using a semiquantitative polymerase chain reaction of intracellular viral DNA established by us and also other methods. Vero cells were infected with HSV-2 strains: either the standard strain 169, or the acyclovir-resistant strain YS-4C-1. PM-19 was added at various stages during the replication of HSV-2. PM-19 strongly inhibited the synthesis of viral genomic DNA when it was added at the time of infection. The addition of PM-19 60–90 min after viral inoculation time-dependently decreased the antiviral activity and increased the relative yield of viral DNA, and the addition of PM-19 was completely ineffective at times later than 90 min. These results suggested that PM-19 inhibited viral penetration but did not affect the synthesis of viral DNA. Furthermore, PM-19 strongly inhibited a second round of infection.
Neoadjuvant Treatment with Weekly High-Dose 5-Fluorouracil as 24-Hour Infusion, Folinic Acid and Oxaliplatin in Patients with Primary Resectable Liver Metastases of Colorectal Cancer
Authors: Wein A. , Riedel C. , Brückl W. , Merkel S. , Ott R. , Hanke B. , Baum U. , Fuchs F. , Günther K. , Reck T. , Papadopoulos T. , Hahn E.G. , Hohenberger W.
Published: April 2003

Purpose: To evaluate the efficacy and safety of neoadjuvant treatment comprising weekly high-dose 5-fluorouracil (5-FU) as a 24-hour infusion, folinic acid (FA) and biweekly oxaliplatin (L-OHP), followed by metastatic resection in patients with primarily resectable liver metastases of colorectal cancer (CRC). Patients and Methods: 20 patients with primarily resectable liver metastases of CRC were enrolled in a prospective phase II study. On an outpatient basis, the patients received a treatment regimen comprising biweekly 85 mg/m2 L-OHP in the form of a 2-hour intravenous infusion and 500 mg/m2 FA as a 1- to 2-hour intravenous infusion, followed by 2,600 mg/m2  5-FU administered as a 24-hour intravenous infusion once weekly. A single treatment cycle comprised one infusion per week during a period of 6 weeks followed by a 2-week rest. Two cycles were administered, with a third being added when the treatment was well tolerated. Thereafter, curative resection of the liver metastases was attempted, and the patients were followed up. Results: After neoadjuvant therapy, 2 of the original 20 patients showed complete remission (CR; 10%) and 18 patients partial remission (PR; 90%). As the main symptom of toxicity, diarrhea (CTC toxicity grade 3–4) was observed in 6 patients (30%), followed by vomiting in 3 patients (15%). The curative resectability rate was 80% (16 of 20). In 9 of 18 patients (50%) undergoing surgical intervention, mild postoperative complications, mainly wound healing disturbances (n = 5), occurred. No postoperative mortality was observed. Over a median follow-up of 23 months (12–38) 6 of 16 curatively resected patients developed distant metastases and 1 patient a local pelvic recurrence. The 2-year disease-free survival rate was 52% and the 2-year cancer-related survival rate 80%. Conclusion: The neoadjuvant treatment with weekly high-dose 5-FU in the form of a 24-hour infusion combined with FA and L-OHP is very effective and well tolerated. Surgical morbidity does not appear to be increased by the neoadjuvant treatment.
Prevention of Peritoneal Metastasis of Human Gastric Cancer Cells in Nude Mice by S-1, a Novel Oral Derivative of 5-Fluorouracil
Authors: Mori Takuji , Fujiwara Yoshiyuki , Yano Masahiko , Tamura Shigeyuki , Yasuda Takushi , Takiguchi Shuji , Monden Morito
Published: April 2003

Objective: Recent clinical trials have suggested that oral administration of a new anti-cancer agent, S-1, seems a promising therapy for advanced gastric cancer. In this study, we assessed the efficacy of S-1 against peritoneal dissemination of gastric cancer in a newly developed animal model and investigated the efficacy of S-1 from a pharmacokinetic angle. Methods: Human gastric cancer cells (MKN-45) were injected into the peritoneal cavity of nude mice. The cancer cells were transduced using an enhanced green fluorescent protein (EGFP)-expressing plasmid vector, enabling micrometastatic foci to be accurately assessed with a high level of detection sensitivity. To investigate pharmacokinetics, the concentration of 5-FU was determined in tumor, peritoneum and plasma. Results: Fourteen and 21 days after intraperitoneal injection, a significant difference in the number of fluorescent foci was observed between the control group and the S-1 group (p = 0.02 and p = 0.0024, respectively. The therapeutic effect of S-1 was significantly greater than that of 5-FU. Furthermore, S-1 treatment greatly improved the survival time and cachexia. The area under the curve of 5-FU in tumor was higher than in the peritoneum and plasma. Conclusion: Oral S-1 is a promising chemotherapy for peritoneal dissemination of gastric cancer.
Immunomagnetic Tumor Cell Enrichment Is Promising in Detecting Circulating Breast Cancer Cells
Authors: Hu X.C. , Wang Y. , Shi D.R. , Loo T.Y. , Chow L.W.C.
Published: April 2003

Objective: Magnetic-activated cell separation (MACS) for the enrichment of tumor cells was evaluated with immunocytochemistry (ICC) and flow cytometry (FCM). Methods: Blood (20 ml) was sampled in 36 affected patients before surgery. Nucleated blood cells were obtained with the removal of red blood cells in the buffy coat. Nucleated blood cells (2 × 106) from breast cancer patients were aliquoted before enrichment for direct immunostaining (ICC group), while all remaining cells were enriched and then immunostained (MACS/ICC group). Breast cancer cell lines were spiked serially in normal nucleated blood cells for FCM evaluation of the enrichment efficiency of MACS. Results: The enrichment rate of spiked tumor cells was 37- to 2,300-fold and was negatively correlated with the ratio of tumor cells to normal nucleated cells (p < 0.05). The positive rate was only 5.6% (2/36) in the ICC group and was as high as 38.9% (14/36) in the MACS/ICC group (p < 0.001). The positivity in the enriched fraction was 0% (0/4), 33.3% (8/24), 60% (3/5) and 100% (3/3) for tumors at stages I, II, III and IV, respectively (p < 0.05). Conclusion: MACS can enrich circulating tumor cells, and the presence of circulating breast cancer cells correlates with clinical staging.
Downregulation of CYP2D16 by ACTH in the Guinea Pig Adrenal Cortex: Time Course, Reversibility, and Mechanism of Action
Authors: Colby Howard D. , Longhurst Penelope A. , Burczynski Joseph M. , Hayes Jill R. , Yuan Bing-Bing , Voigt Jeffrey M.
Published: April 2003

Studies were done to investigate the actions of ACTH on the expression of CYP2D16 in the guinea pig adrenal cortex. Guinea pigs were treated with ACTH for 1, 3, or 7 days. In addition, some animals received ACTH for 7 days and were then untreated for an additional 3 or 7 days to test for reversibility of ACTH actions. ACTH treatment caused a time-dependent decrease in the rates of adrenal microsomal bufuralol metabolism, a CYP2D-catalyzed reaction; hepatic bufuralol metabolism was unaffected by ACTH. Adrenal enzyme activity was significantly reduced by ACTH within 1 day and decreased by 80% after 7 days. Western blotting and in situ hybridization analyses revealed corresponding declines in adrenal CYP2D16 protein and mRNA concentrations. Nuclear runoff assays indicated that ACTH treatment inhibited CYP2D16 expression at the transcriptional level. Adrenal 17α-hydroxylase activities were increased by ACTH treatment, but CYP17 protein concentrations were not affected. Following cessation of ACTH administration, the rates of adrenal bufuralol metabolism and CYP2D16 protein and mRNA concentrations returned to control levels within 7 days. The results demonstrate that ACTH has a relatively rapid and reversible effect to inhibit adrenal CYP2D16 transcription, thereby decreasing adrenal xenobiotic metabolism. Thus, the actions of ACTH on CYP2D16 expression are opposite to those on other adrenal P-450 isozymes, indicating unique regulatory mechanisms.
Cardioprotective Effects of Extracts from Psidium guajava L. and Limonium wrightii, Okinawan Medicinal Plants, against Ischemia-Reperfusion Injury in Perfused Rat Hearts
Authors: Yamashiro Satoshi , Noguchi Katsuhiko , Matsuzaki Toshihiro , Miyagi Kanako , Nakasone Junko , Sakanashi Mayuko , Sakanashi Makiko , Kukita Ichiro , Aniya Yoko , Sakanashi Matao
Published: April 2003

The aim of this study was to determine whether the medicinal herbs growing in Okinawa and possessing a radical-scavenging activity would exert cardioprotective effects against ischemia-reperfusion injury using isolated perfused rat hearts. Effects of the aqueous extracts from Psidium guajava L. and Limonium wrightii at concentrations having an equipotent radical-scavenging activity on myocardial injury produced by global ischemia followed by reperfusion were tested and were further compared with those of quercetin and gallic acid, major antioxidative components of P. guajava L. and L. wrightii, respectively. Both extracts significantly attenuated ischemic contracture during ischemia and improved myocardial dysfunction after reperfusion. Decreases in high-energy phosphates and increases in malondialdehyde in the reperfused hearts were significantly lessened with both plant extracts. Quercetin and gallic acid also exerted similar beneficial effects. These results indicate that P. guajava L. and L. wrightii both have cardioprotective effects against myocardial ischemia-reperfusion injury in isolated rat hearts, primarily through their radical-scavenging actions.
Sildenafil, a Phosphodiesterase-5 Inhibitor, Enhances the Antinociceptive Effect of Morphine
Authors: Jain Naveen K. , Patil C.S. , Singh Amarjit , Kulkarni Shrinivas K.
Published: April 2003

Various evidence has demonstrated a role of the nitric oxide (NO)/cGMP signaling pathway in the processing of nociception. The exact role of phosphodiesterase-5 (PDE-5) via the NO/cGMP pathway is not fully understood in pain response. The aim of the present study was to investigate the possible peripheral interaction between a PDE-5 inhibitor (sildenafil) and morphine. Carrageenan-induced hyperalgesia in rats and the acetic-acid-induced writhing test in mice were used as animal models. Local administration of sildenafil (50–200 µg/paw, i.pl.) exhibited a dose-dependent antinociceptive effect against the paw pressure test. Sildenafil also demonstrated an antinociceptive effect (1–10 mg/kg, i.p.) against in the writhing test. Co-administration of sildenafil (100 µg/paw, i.pl. and 2 mg/kg, i.p.) significantly enhanced the antinociceptive effect of morphine (2 µg/ paw, i.pl. and 2 mg/kg, i.p respectively). The antinociception produced by the drugs alone or combined was due to a local action, as its administration in the contralateral paws was ineffective. Pretreatment with NG-nitro-L-arginine methyl ester (an NO synthesis inhibitor), methylene blue (gunalyl cyclase inhibitor) or naloxone (opioid receptor antagonist) blocked the effect of a sildenafil-morphine combination in both tests. The results suggest that opioid receptor (NO and cGMP) mechanisms are involved in the combined antinociceptive effect. Further, sildenafil produced antinociception per se and increased the response of morphine, probably through the inhibition of cGMP degradation.
Acne in Infancy and Acne Genetics
Authors: Herane Maria I. , Ando Iwao
Published: April 2003

Acne is a disease that can be seen in the first year of age, early childhood, prepubertal age and puberty. Neonatal acne is due mainly to considerable sebum excretion rate, and infantile acne because of high androgens of adrenal origin in girls and of adrenal and testes in boys. These pathogenic mechanisms are characteristic in these ages. Important factors like early onset of comedones and high serum levels of dehydroepiandrosterone sulfate are predictors of severe or long-standing acne in prepubertal age. Hereditary factors play an important role in acne. Neonatal, nodulocystic acne and conglobate acne has proven genetic influences. Postadolescent acne is related with a first-degree relative with the condition in 50% of the cases. Chromosomal abnormalities, HLA phenotypes, polymorphism of human cytochrome P-450 1A1 and MUC1 gene are involved in the pathogenesis of acne. Several other genes are being studied.
Update and Future of Systemic Acne Treatment
Authors: Zouboulis Christos C. , Piquero-Martin Jaime
Published: April 2003

Systemic treatment is required in patients with moderate-to-severe acne, especially when acne scars start to occur. Antibiotics with anti-inflammatory properties, such as tetracyclines (oxytetracycline, tetracycline chloride, doxycycline, minocycline and limecycline) and macrolide antibiotics (erythromycin and azithromycin) are the agents of choice for papulopustular acne, even though the emerging resistant bacterial strains are minimizing their effect, especially regarding erythromycin. Systemic antibiotics should be administered during a period of 8–12 weeks. In severe papulopustular and in nodulocystic/conglobate acne, oral isotretinoin is the treatment of choice. Hormonal treatment represents an alternative regimen in female acne, whereas it is mandatory in resistant, severe pubertal or post-adolescent forms of the disease. Compounds with anti-androgenic properties include estrogens combined with progestins, such as ethinyl estradiol with cyproterone acetate, chlormadinone acetate, desogestrel, drospirenone, levonogestrel, norethindrone acetate, norgestimate, and other anti-androgens directly blocking the androgen receptor (flutamide) or inhibiting androgen activity at various levels, corticosteroids, spironolactone, cimetidine, and ketoconazole. After 3 months of treatment control of seborrhea and acne can be obtained. Low-dose corticosteroids (prednisone, prednisolone, or dexamethasone) are indicated in patients with adrenal hyperandrogenism or acne fulminans. New developments and future trends represent low-dose long-term isotretinoin regimens, new isotretinoin formulations (micronized isotretinoin), isotretinoin metabolites, combination treatments to reduce toxicity, insulin-sensitizing agents, 5α-reductase type 1 inhibitors, antisense oligonucleotide molecules, and, especially, new anti-inflammatory agents, such as lipoxygenase inhibitors.
Propionibacterium acnes Resistance: A Worldwide Problem
Authors: Eady E.A. , Gloor M. , Leyden J.J.
Published: April 2003

Antibiotic therapy directed against Propionibacterium acnes has been a mainstay of treatment for more than 40 years. Despite years of widespread use of systemic tetracyclines and erythromycin, change in P. acnes sensitivity to antibiotics was not seen until the early 1980s. The first clinically relevant changes in P. acnes antibiotic sensitivity were found in the USA shortly after the introduction of topical formulations of erythromycin and clindamycin. By the late 1980s, P. acnes strains with very high MIC levels for erythromycin and elevated MICs for tetracycline were increasingly found in the UK and the USA. Mutations in the genes encoding the 23S and 16S subunits of ribosomal RNA were first identified in the UK and also seen in a recent survey from clinics in Europe, Japan, Australia and the USA. In addition, strains were found in which these known mutations could not be identified, indicating that as yet unidentified resistance mechanisms have evolved. These findings indicate the need to develop strategies to minimize the use of antibiotics in acne therapy.
Type 2 Diabetes mellitus in Children and Adolescents: A Review from a European Perspective
Authors: Kiess W. , Böttner A. , Raile K. , Kapellen T. , Müller G. , Galler A. , Paschke R. , Wabitsch M.
Published: April 2003

Changes in food consumption and exercise are fuelling a worldwide increase in obesity in children and adolescents. As a consequence of this dramatic development, an increasing rate of type 2 diabetes mellitus has been recorded in children and adolescents in the USA and, more recently, in many countries around the world. Both genetic and environmental factors contribute to the pathogenesis of type 2 diabetes. Lower susceptibility in white Caucasians and higher susceptibility in Asians, Hispanics and blacks have been noted. There is a high hidden prevalence and a lack of exact data on the epidemiology of the disease in Europe: in Germany only 70 patients below the age of 15 years were identified in the systematic, nationwide DPV (Diabetessoftware für prospektive Verlaufsdokumentation) diabetes survey, but our calculations suggest that more than 5000 young people in Germany at present would meet the diagnostic criteria of type 2 diabetes. In Australasia, the prevalence of type 2 diabetes is reportedly high in some ethnic groups and again is linked very closely to the obesity epidemic. No uniform and evidence-based treatment strategy is available: many groups use metformin, exercise programmes and nutritional education as a comprehensive approach to treat type 2 diabetes in childhood and adolescence. The lack of clear epidemiological data and a strong need for accepted treatment strategies point to the key role of preventive programmes. Prevention of obesity will help to counteract the emerging worldwide epidemic of type 2 diabetes in youth. Preventive programmes should focus on exercise training and reducing sedentary behaviour such as television viewing, encouraging healthy nutrition and supporting general education programmes since shorter school education is clearly associated with higher rates of obesity and hence the susceptibility of an individual to acquire type 2 diabetes.
Impact of Cancer Therapy on the Reproductive Axis
Authors: Müller Jørn
Published: April 2003

Cancer therapy includes surgery, chemotherapy and irradiation. Depending on the diagnosis, the location of the neoplasm and the age of the patient, these treatment modalities may be given alone or in combination. All forms of cancer therapy can affect the hypothalamic-pituitary-gonadal axis. The long-term consequences for reproductive function depend on several aspects. The sex of the patient is important, since ovarian and testicular function differ significantly. Sex hormone production in the female is dependent on the presence of germ cells, whereas this is not the case in the male. The sensitivity of germ cells to cancer therapy also differs between the sexes. Moreover, the sensitivity of both the hypothalamic-pituitary axis and the gonads is highly age dependent. With regard to chemotherapy, the possible damage to the gonads is dependent on the total dose and type of agent given. According to current knowledge, the hypothalamic-pituitary axis is not affected by conventional doses of chemotherapy. Radiotherapy has by far the most damaging effect on the reproductive axis, having serious adverse effects on both the hypothalamic-pituitary area as well as on the gonads themselves. The harmful effect of irradiation depends on the total dose of irradiation, the radiation field, as well as the number and size of fractions given. The long-term consequences of recently introduced radiotherapeutic methods such as stereotactic irradiation are not yet known. The present review will focus on the late effects of cancer therapy in children and young adults with acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, brain tumour, Hodgkin’s lymphoma or Wilms’ tumour, including the adverse effects of bone marrow transplantation.
Neonatal Thyroid Disorders
Authors: Grüters Annette , Biebermann Heike , Krude Heiko
Published: April 2003

Congenital hypothyroidism is the most prevalent endocrine disorder in the newborn and affects 1 in 3,000–4,000 newborns. Screening for congenital hypothyroidism is a major achievement of paediatrics because early diagnosis and treatment have resulted in normal development in nearly all cases. The cause of congenital hypothyroidism in the majority of newborns is unknown. However, in some patients the molecular basis of their congenital hypothyroidism has recently been clarified. In patients with congenital hypothyroidism and a normally developed thyroid gland, the autosomal recessive inheritance of loss-of-function mutations of genes encoding for the thyroid peroxidase gene, the sodium-iodide symporter gene and the pendrin gene have been identified. The autosomal recessive inheritance of loss-of-function mutations of the thyroid stimulating hormone (TSH) receptor as well as the dominant inheritance of mutations encoding for transcription factors have been identified in patients with defective thyroid development. Furthermore, it has become evident that in some patients with persistent mental retardation and neurological symptoms, defects of the transcription factor NKX2.1, which is expressed in the thyroid gland as well as in the CNS during embryonic development, cause both defective thyroid and CNS development resulting in persistent neurological and mental defects despite early diagnosis and treatment. Central hypothyroidism is a rare disease with an estimated frequency of not more than 1 in 50,000 newborns. Central hypothyroidism can be due to recessive inheritance of loss-of-function mutations of the TSH-β gene and to developmental defects of the hypothalamus or pituitary. In contrast to the previous assumption that isolated TSH deficiency will not lead to impaired mental development, identification of the molecular defects in central hypothyroidism has clearly demonstrated that some of these patients will have impaired mental development. Clarification of the molecular defects of thyroid development will help to explain the differences in outcome in patients with congenital hypothyroidism and to develop new diagnostic and therapeutic strategies to ensure adequate counselling and care for these patients.
Intellectual and Psychological Performance in Males Born Small for Gestational Age
Authors: Lundgren E.M. , Cnattingius S. , Jonsson B. , Tuvemo T.
Published: April 2003

All male singletons born without congenital malformations in Sweden between 1973 and 1978 and conscripted between January 1991 and January 1997 (n = 254,426) were studied. Intellectual and psychological performance was tested at conscription. Males born small for gestational age (SGA) had lower results on both intellectual and psychological performance testing. Among males born SGA, low mean scores in both tests were constantly more common in those without catch-up growth than in those with catch-up growth. In conclusion, being born SGA is associated with an increased risk of subnormal intellectual and psychological performance. Catch-up growth is associated with a reduced risk of subnormal performance in males born SGA.
Blood Purification in Non-Renal Critical Illness
Authors: Kellum John A. , Bellomo Rinaldo , Mehta Ravindra , Ronco Claudio
Published: April 2003

Extracorporeal therapies designed to remove substances from the circulation now include hemodialysis, hemofiltration, hemoadsorption, plasma filtration, cell-based therapies and combinations of any of the above. In recent years, there have been considerable advances in our understanding and technical capabilities, but consensus over the optimal way, and under what conditions to use these therapies does not exist. Consequently, we have initiated a series of conferences under the auspices of the Acute Dialysis Quality Initiative (ADQI). ADQI aims at establishing an evidence-based appraisal and set of consensus recommendations to standardize care and direct further research. The results of previous consensus conferences are available on-line at www.ADQI.net. ADQI conferences have focused on research and management of renal disease. However, extracorporeal therapies are being used or investigated in the management of many other disease processes including systemic inflammation, liver disease, cardiac disease and thrombotic diseases.
Effectiveness of Hormonal Tourniquet by Vasopressin during Myomectomy through Vasopressin V1a Receptor Ubiquitously Expressed in Myometrium
Authors: Kimura Tadashi , Kusui Chika , Matsumura Yoko , Ogita Kazuhide , Isaka Sigeyuki , Nakajima Atsuko , Ohashi Kazutomo , Koyama Masayasu , Azuma Chihiro , Murata Yuji
Published: April 2003

To elucidate the mechanism by which myometrial vasopressin injection promotes hemostasis during myomectomy, we examined the expression of vasopressin V1a receptor transcripts in the myometrium. Vasopressin V1a receptor expression was ubiquitous, and the transcripts were detected in the myometrium not only of cycling and pregnant patients, but also of postmenopausal or GnRH agonist-treated patients. Based on these observations, we applied intraoperative myometrial vasopressin injection during myomectomy in a non-randomized study in a total of 84 patients. Vasopressin injection significantly reduced the intraoperative blood loss and postoperative hemoglobin fall in patients without and with GnRH agonist pretreatment. No serious complications occurred on account of the vasopressin injection. We conclude that intraoperative vasopressin injection is effective as a hormonal tourniquet even in GnRH agonist-pretreated myomectomy.