bluuebunny/crossref_metadata_2025 huggingface dataset:
A Phase I–II Study on a Gemcitabine-Cyclophosphamide-Fluorouracil/Folinic Acid Triplet Combination in Anthracycline- and Taxane-Refractory Breast Cancer Patients
Authors: Frasci Giuseppe , D’Aiuto Giuseppe , Comella Pasquale , Thomas Renato , Capasso Immacolata , Botti Gerardo , Cortino Giuseppina Rosa , Di Bonito Maurizio , Rubulotta Rosaria , Vallone Paolo , Comella Giuseppe
Published: April 2003

Purpose: To define the cyclophosphamide (CTX) maximal tolerated dose when combined with fixed doses of gemcitabine, fluorouracil (5-FU) and folinic acid (leucovorin, LFA) in metastatic breast cancer patients pretreated with anthracyclines and taxanes. Methods: Metastatic breast cancer patients aged ≤75 years, with ECOG performance status 0–2, were eligible, provided that they had received previous anthracycline- and taxane-based chemotherapy for the advanced disease. Chemotherapy consisted of gemcitabine 1,000 mg/m2, 5-FU 425 mg/m2, LFA 100 mg/m2 and escalating doses of CTX, starting from 500 mg/m2, on days 1 and 8 every 3 weeks. The dose escalation was stopped if dose-limiting toxicity (DLT) occured in >33% of patients of a given cohort. After the definition of DLT, a further escalation with the addition of granulocyte colony-stimulating factor (G-CSF; on days 3–5 and 10–12) was planned. Results: Since March 1999, 69 patients have entered this trial through seven different cohorts. The dose escalation was stopped at the CTX dose of 600 mg/m2 since 3/6 patients showed DLT. A further dose escalation was attempted in the presence of G-CSF support. A CTX dose of 800 mg/m2 proved to be safe and was chosen for the phase II. A total of 33 patients were treated at this dose level. The treatment was fairly well tolerated, grade 3–4 neutropenia and thrombocytopenia occurring in 38 and 16% of patients, respectively. No cases of sepsis or bleeding were registered. Four patients required a packed red blood cell transfusion. Severe nonhematologic toxicity was also uncommon, occuring in 10 patients. Three complete and 24 partial responses were recorded for an overall response rate of 38% (95% CI = 26–50). Two complete and 12 partial responses were recorded in the 33 patients treated in the phase II for an overall response rate (ORR) of 42% (95% CI = 25–61). Conclusions: The gemcitabine-CTX-5-FU/LFA combination is a well-tolerated treatment for poor-prognosis breast cancer patients with previous exposure to anthracyclines and taxanes. With the addition of G-CSF, a cumulative CTX dose of 1,600 mg/m2 can be safely delivered every 3 weeks. The evidence of an ORR approaching 40% is very promising and justifies further evaluations in this subset of patients.
Expression of Cyclooxygenase-2 Is Associated with Carcinogenesis of the Lower Part of Thoracic Esophageal Squamous Cell Carcinoma and p53 Expression
Authors: Kawabe Atsushi , Shimada Yutaka , Uchida Shigeki , Maeda Masato , Sato Fumiaki , Itami Atsushi , Imamura Masayuki
Published: April 2003

Cyclooxygenase (COX) is a key enzyme in arachidonic acid metabolism. Two isoforms of this enzyme have been identified: constitutive COX-1 and inducible COX-2. Recently, expression of COX-2 has been found in several human carcinomas. COX-2 expression may contribute to the synthesis of prostanoids, which relate to carcinogenesis and tumor progression. We investigated the expression of COX-2 in 175 human esophageal squamous cell carcinoma tissues using immunohistochemistry and evaluated the relationship with clinicopathological findings. In addition, due to the known relevance of p53 to carcinogesis, we evaluated the expression of COX-2 and p53. Interestingly, cancer tissues with high COX-2 expression were found significantly more often in the middle and lower esophagus than in the cervical and upper esophagus (p = 0.0014). No significant differences were observed in other clinicopathological data such as age, sex, histopathological grading, lymphatic invasion, venous invasion, TNM clinical classification and patient prognosis. p53 expression was associated with the expression of COX-2 (p = 0.0122). Our findings suggest that COX-2 may play a role in the development of squamous cell carcinoma in the lower part of the thoracic esophagus.
Acridine Orange Excited by Low-Dose Radiation Has a Strong Cytocidal Effect on Mouse Osteosarcoma
Authors: Hashiguchi Shin , Kusuzaki Katsuyuki , Murata Hiroaki , Takeshita Hideyuki , Hashiba Mitsuoki , Nishimura Tsunehiko , Ashihara Tsukasa , Hirasawa Yasusuke
Published: April 2003

The study was conducted to clarify the cytocidal effect of combination therapy consisting of administration of acridine orange (AO), which is a photosensitizer, and radiation therapy using in vitro and in vivo mouse osteosarcoma models. The results revealed that AO combined with low-dose X-ray irradiation of about 1–5 Gy had a strong cytocidal effect on the cultured mouse osteosarcoma cells regardless of their chemosensitivity, and that this combination therapy inhibited growth of the in vivo mouse osteosarcoma by induction of tumor necrosis. This effect was inhibited by L-histidine, but not by mannitol. These findings suggested that AO might be excited by X-rays and kill osteosarcoma cells through the release of singlet oxygen, which is toxic to living cells. This mechanism is similar to that of photodynamic therapy with AO.
Prognostic Impact of Multiple Allelic Losses on Metastatic Recurrence in Hepatocellular Carcinoma after Curative Resection
Authors: Nishida Naoshi , Fukuda Yoshihiro , Komeda Toshiki , Ito Teruaki , Nishimura Takafumi , Minata Mutsuko , Kuno Masato , Katsuma Hirokazu , Ikai Iwao , Yamaoka Yoshio , Nakao Kazuwa
Published: April 2003

Loss of heterozygosity (LOH) on chromosomes 13q, 16q and 17p has been associated with the progression of hepatocellular carcinoma (HCC). To investigate the prognostic impact of such LOH, we examined the metastasis-free survival of curatively resected HCC cases, in whom these LOHs were analyzed. Among the 49 HCC patients examined, the frequency of LOHs was 28% on 13q, 33% on 16q and 40% on 17p. The patients were followed up for metastatic recurrence after surgery and for analysis of the relationship between chromosomal changes and patients’ metastasis-free survival. Univariate survival analysis showed the presence of LOH on 16q, 17p and the number of chromosomes with LOH were significantly and negatively associated with metastasis-free survival, indicating that patients with LOH on multiple chromosomes had a poorer prognosis after surgery than those with LOH on a single chromosome or no LOH. Multivariate Cox survival analysis identified the presence of LOH on 16q and the number of chromosomes with LOH as the most significant independent negatively predictive factors for metastasis-free survival. These findings indicate that accumulation of chromosomal changes is associated with metastatic behavior, and that LOH on 16q was the most useful prognostic indicator for metastasis after curative resection of HCC.
Prognostic Significance of the Thymidylate Biosynthetic Enzymes in Human Colorectal Tumors
Authors: Kralovánszky Judit , Köves István , Orosz Zsolt , Katona Csilla , Tóth Katalin , Rahóty Pál , Czeglédi Ferenc , Kovács Tibor , Budai Barna , Hullán Lehel , Jeney András
Published: April 2003

The aim of the present study was to determine the relative intratumoral activity of two pyrimidine biosynthetic enzymes, i.e. thymidylate synthase (TS) and thymidine kinase (TK), in human colorectal cancers to compare their possible relationship with demographic and pathologic characteristics of the patients and their tumors, and moreover to evaluate their predictive significance regarding 5-fluorouracil (5-FU) sensitivity and the overall survival of patients, respectively. TS and TK levels were significantly increased in the tumor compared to peritumoral tissue. However, no significant relationship between TS/TK activity and demographic features of the patients or pathologic characteristics of their tumors could be demonstrated. Kaplan-Meier analysis showed that the overall survival of patients with low TS activity was significantly longer (p < 0.012) compared to those with high TS activity. Such a difference could not be demonstrated between patients with high or low TK activity; however, combined evaluation of the two parameters proved that TK may contribute to the more precise assessment of disease prognosis, and it may further influence treatment decisions, i.e. the selection of patients for adjuvant therapy with 5-FU and folinic acid. Multivariate analysis showed that among the variables tested, beside Dukes’ stage, TS and TK activities were significant prognostic factors for the overall survival of colorectal cancer patients.
Establishment of a New Cell Line (TAYA) of Clear Cell Adenocarcinoma of the Ovary and Its Radiosensitivity
Authors: Saga Yasushi , Suzuki Mitsuaki , Machida Shizuo , Ohwada Michitaka , Sato Ikuo
Published: April 2003

A new cell line (TAYA) was established from ascites of a patient with clear cell adenocarcinoma of the ovary, and the sensitivity of the cell line to various anticancer drugs and radiation was investigated. The 50% growth inhibitory concentrations (IC50) (nM) of various anticancer drugs were: cisplatin >10,000, paclitaxel 80, SN-38 (irinotecan metabolite) 460, and gemcitabine >10,000, showing that the cells had a low sensitivity to these anticancer drugs. In contrast, the 50% growth inhibitory dose (ID50) of radiation was 1.8 Gy, showing that the cells were highly sensitive to radiation. Thus, radiotherapy may be effective for treatment of clear cell adenocarcinoma of the ovary.
Selection of Scleral Buckling for Primary Retinal Detachment
Authors: Ho Cheng-Lien , Chen Kwan-Jen , See Lai-Chu
Published: April 2003

Purpose: Rhegmatogenous retinal detachment (RRD) may be caused by a flap tear or by an atrophic hole along the lattice degeneration. The aim of this study was to see whether different types of scleral buckling could achieve comparable reattachment rates in eyes with specific types of RRD. Patients and Methods: 128 eyes with RRD were assigned to receive 1 of 3 buckling procedures according to the following guidelines: retinal detachments caused by flap tears were treated with radial segmental buckling; retinal detachments caused by atrophic holes with limited lattice degeneration were treated with circumferential segmental buckling, and retinal detachments caused by multiple breaks with extensive lattice degeneration were treated with encircling buckling. Results: 56 eyes received radial segmental buckling, 36 eyes received circumferential segmental buckling, and 36 eyes received encircling buckling. The reattachment rates in these three groups were 83.9, 86.1, and 88.9%, respectively (no statistically significant difference). The visual outcomes were comparable in all groups. Younger age, an increased requirement for subretinal fluid drainage, longer operation time, and myopic shift were noted in the encircling group. Conclusions: Comparable reattachment rates could be achieved in all three groups according to our guidelines. Segmental buckling is appropriate for two thirds of RRD in this study and has fewer complications than encircling buckling. Every retinal detachment behaves differently and should be subjected to its optimal buckling procedure to achieve the best results and to avoid unnecessary operative complications.
Impact of Increased Intraocular Pressure on Long-Term Corneal Endothelial Cell Density after Penetrating Keratoplasty
Authors: Nguyen N.X. , Langenbucher A. , Seitz B. , Küchle M. , Naumann G.O.H.
Published: April 2003

Purpose: Besides immunological graft rejection, persistently increased intraocular pressure (IOP) is among the most important causes for graft failure after penetrating keratoplasty (PK). The purpose of this study was to assess the longitudinal development of IOP after PK and to investigate possible correlations with corneal endothelial cell density. Methods: This longitudinal prospective study included 209 eyes after PK with a complete follow-up at 3 months, 6 months, before first suture removal (16 ± 5 months) and after complete suture removal (21 ± 5 months). At each examination, IOP was measured by Goldmann applanation tonometry. Endothelial cell density was assessed by specular microscopy (EM 1100, Tomey). The indications for PK were 48% keratoconus, 34% Fuchs’ dystrophy, 5.4% stromal dystrophies, 8.6% secondary bullous keratopathy and 4% corneal scars. An iridotomy was performed routinely during PK. The postoperative treatment with topical steroids was standardized. Results: Preoperatively, the mean IOP was 13.6 ± 2.9 mm Hg with increased IOP (>21 mm Hg) in 2.0% of eyes. After 3 months, the incidence of increased IOP (24.5 ± 4.6 mm Hg) was highest (6.7%) and decreased thereafter to 3.0% after complete suture removal. No patients showed IOP higher than 30 mm Hg. A persistently increased IOP for more than 3 months was seen in 2% of patients. At 3 months postoperatively, the mean endothelial cell density was 1,977 ± 496/mm2 and did not decrease significantly (p > 0.05) until 6 months (1,771 ± 507 cells/mm2). At the end of the follow-up period, the mean endothelial cell density was significantly reduced (1,347 ± 501 cells/mm2). There was no significant correlation between IOP and mean endothelial cell density at any postoperative examination stage (p > 0.24). Patients with persistently increased IOP for more than 3 months did not have significantly different endothelial cell densities in comparison with those without increased IOP. Conclusion: From 6 months after PK, the incidence of increased IOP was not higher than the preoperative level. Mild to moderate temporary IOP elevations after PK do not seem to affect the endothelial cell density of the graft until complete suture removal. Further long-term studies are necessary to assess the clinical relevance of these observations.
A Comparison of the Short-Term Hypotensive Effects and Side Effects of Unilateral Brimonidine and Apraclonidine in Patients with Elevated Intraocular Pressure
Authors: Yüksel Nurşen , Karabaş Levent , Altıntaş Özgül , Yildirim Yusuf , Çağlar Yusuf
Published: April 2003

Purpose: To compare the short-term ocular hypotensive efficacy and side effects of 0.2% brimonidine and 0.5% apraclonidine in patients with elevated intraocular pressure (IOP). Methods: We performed a double-masked, placebo-controlled study to compare the efficacy of the application of 0.2% brimonidine and 0.5% apraclonidine for the effect of IOP, systemic blood pressure and heart rate in 20 newly diagnosed ocular hypertensive patients. Effects on the untreated fellow eye and ocular side effects were also determined. All measurements were performed 1, 2, 4, 6 and 8 h after the instillation of one drop. Results: Brimonidine and apraclonidine significantly reduced IOP from baseline at all observation times. No significant difference was observed between the treatment groups. IOP decreased significantly in the untreated fellow eye in the brimonidine group at 4-, 6- and 8-hour checks and at 6-hour checks in the apraclonidine group when compared with placebo. Blood pressure and heart rate decreased significantly in the brimonidine group compared with placebo. Apraclonidine did not affect blood pressure or heart rate any differently than placebo. The pupil diameter and the interpalpebral fissure width significantly increased in the apraclonidine group, but not in the brimonidine group. There were no significant differences in the overall incidence of foreign body sensation, burning and stinging and dry mouth in the treatment groups. Conclusions: In the short-term, brimonidine was effective in reducing IOP in patients with elevated IOP and was equivalent in efficacy to apraclonidine. On the other hand, a significant change in blood pressure and heart rate was observed with brimonidine; there was no change at all in the apraclonidine group.
Effect of Sympathetic Denervation on Rabbit Choroidal Blood Flow
Authors: Chou Ping-I , Lu Da-Wen , Chen Jiann-Torng
Published: April 2003

In this study we demonstrate the existence of sympathetic innervation and compare the effect of unilateral or bilateral superior cervical sympathectomy on albino rabbit choroidal blood flow (CBF) during changes in perfusion pressure (PP). Forty albino rabbits weighing between 2.0 and 3.0 kg were randomly divided into three groups. The bilateral sympathectomy group (group S) included 10 rabbits (20 eyes) that received bilateral sympathectomy 1 week prior to the study. The unilateral sympathectomy group (group U) included 20 rabbits (20 eyes) that received unilateral sympathectomy 1 week prior to the study. Only the eyes ipsilateral to sympathectomy were utilized. The other 10 rabbits (20 eyes) served as controls (group N), each received the same procedure as the experimental groups except that the superior cervical ganglion (SCG) was preserved. The blood cell flux (PF), velocity (V), and concentration of moving blood cells (CMBC) were recorded simultaneously by means of a laser Doppler flowmeter (Perimed PF4001), while the intraocular pressure was increased linearly with a syringe pump. When the PP decreased steadily, the PF, V, and CMBC remained constant until PP <55 mm Hg, then decreased proportionally to the PP. When the PP decreased from 75 to 0 mm Hg, the PF, V and CMBC decreased from 100 to 6.87 ± 0.97%, 8.44 ± 0.92%, and 18.67 ± 0.91% in group N, to 18.56 ± 1.62%, 19.30 ± 1.84%, and 38.02 ± 9.10% in group U, and to 18.38 ± 2.89%, 16.78 ± 1.48%, and 34.58 ± 4.42% in group S. The changes in PF, V, and CMBC were similar in groups S and U. Both group S and U had higher PF, V, and CMBC values than group N at comparable PPs below 55 mm Hg. These results indicate that the SCG plays a role in CBF regulation. Both unilateral and bilateral sympathectomy led to a higher PF in both groups S and U rabbits, indicating increased CBF while PP decreased gradually. This suggests that the rabbit choroid does not receive crossed innervation. The plateau response in each curve demonstrates the presence of autoregulation. This autoregulation was unchanged by either unilateral or bilateral sympathetic denervation.
Anterior Ischemic Optic Neuropathy Associated with Idiopathic Aldosteronism and Hypertension
Authors: Taniai Mariko , Mizota Atsushi , Adachi-Usami Emiko , Tatsuno Ichiro
Published: April 2003

A 49-year-old man suffered from bilateral anterior ischemic optic neuropathy almost simultaneously, and was diagnosed with idiopathic aldosteronism associated with hypertension. Because this patient had multiple organ disorders, multiple cerebral infarctions, and a mild loss of renal function, it was important to treat his primary disease.
Pyruvate Inhibits Galactosemic Changes in Cultured Cat Lens Epithelial Cells
Authors: Gupta S.K. , Mohanty Ipseeta , Trivedi Deepa , Tandon Radhika , Srivastava Sushma , Joshi Sujata
Published: April 2003

An attempt was made to maintain cat lens epithelial cells (CLEC) in culture and study the morphology, growth and survival of these cells in vitro. The influence of incorporation of galactose (30 mM) into the culture medium on the morphology and biochemistry of CLEC in the primary culture was then investigated. To establish the effect of galactose on CLEC, various biochemical parameters associated with galactosemic cataract such as aldose reductase (AR), Na+K+ATPase, glutathione, polyol and soluble/insoluble proteins were estimated after 24 h of incubation. The effect of pyruvate (5 mM), a ‘physiological antioxidant’, on the changes induced by galactose in CLEC was studied. CLEC in culture showed regular hexagonal cells with prominent nuclei. The CLEC culture attained confluency in 11 days during primary culture and semiconfluency in 14 days in two subsequent passages. Vacuolization and significantly raised AR activity, polyol levels and insoluble protein contents were observed; they had no effect on Na+K+ATPase and soluble protein after 24 h of incubation in the culture medium with galactose. Supplementation of pyruvate (5 mM) resulted in a lesser number of vacuoles together with a positive modulation of these parameters.
Measurement of Cerebrospinal Fluid Output through External Ventricular Drainage in One Hundred Infants and Children: Correlation with Cerebrospinal Fluid Production
Authors: Yasuda Takasumi , Tomita Tadanori , McLone David G. , Donovan Mark
Published: April 2003

Objective: Cerebrospinal fluid (CSF) production rates influence shunt design and the care of children with hydrocephalus. Measurement of hourly CSF output through external ventricular drainage (EVD) reflects the CSF production. In the present study, hourly CSF outputs in children with hydrocephalus were measured while they were treated with EVD and correlated with the age, sex and body weight of the patients as well as other clinical parameters. Methods: One hundred children with hydrocephalus due to various causes had EVD treatment. Twenty-six had EVD on two or three separate occasions; thus, the CSF output measurements were observed and analyzed on the basis of 130 EVDs. The most common reason for EVD treatment was shunt infection (n = 75). The duration of EVDs ranged from 25 to 774 h (mean 269 h). The height of the drip chamber from the mid-head position ranged from 0 to 23 cm (mean 9.8 cm). The hourly CSF output was analyzed according to the patient’s age, sex and body weight as well as the presence of CSF infection. Results: The hourly CSF output rapidly increases during the first year of life. By the second year, it reaches 64% of the hourly CSF output of 15-year-old children. The mean hourly output ranged from 0.1 to 26.5 ml/h (mean 8.1 ml/h), with the standard deviation ranging from 0.4 to 10.8 ml/h (mean 5.2 ml/h). A regression analysis indicated that the age and body weight appeared to correlate with the hourly CSF output. Using the natural logarithm of age, body weight and sex, these predictors accounted for 50.9% of the variability in hourly CSF output. The regression equation is as follows: hourly CSF output = 2.78 – 2.23(male = 0, female = 1) + 0.97 log(age in years) + 2.26 log(body weight in kg). R sd = 3.36, R2 = 0.509. The type of infecting organism and the height of EVD did not influence the overall CSF output. Conclusion: The hourly CSF output fluctuates, but the CSF output increases logarithmically with age and body weight. The gender also influences the CSF output, with males having a greater output than females. The data produced by the present study will help us to understand CSF production rates in developing children. They will also help us in the care of children receiving EVD treatment, as well as in selecting and designing shunt systems.
Cerebral Salt Wasting Syndrome following Brain Injury in Three Pediatric Patients: Suggestions for Rapid Diagnosis and Therapy
Authors: Berkenbosch John W. , Lentz Christopher W. , Jimenez David F. , Tobias Joseph D.
Published: April 2003

The association between hyponatremia and intracranial pathology has been well described. When accompanied by natriuresis, hyponatremia has most commonly been attributed to inappropriate secretion of antidiuretic hormone. However, there is growing evidence to suggest that many of these patients may actually have cerebrally mediated salt losses, a disorder referred to as the cerebral salt wasting syndrome (CSWS). While this syndrome has been reasonably well described in adults, data regarding CSWS in pediatric-aged patients remains sparse. Since fluid management of these disorders is different, it is important that the clinician be able to rapidly differentiate between them. We report three cases of CSWS in acutely brain-injured children and comment on the role that early quantitation of urine volume and urine sodium concentration had in rapidly establishing the correct diagnosis.
Cervical Intramedullary Gliofibroma in a Child
Authors: Matsumura Akira , Takano Shingo , Nagata Michio , Anno Izumi , Nose Tadao
Published: April 2003

A rare case of intramedullary gliofibroma in a 12-year-old girl is reported. MRI revealed an intramedullary tumor with two different intensities, and these portions showed different staining patterns after gadolinium contrast enhancement, with faint enhancement at the periphery and strong enhancement in the central portion. Intraoperatively, the tumor had a relatively clear margin to the spinal cord and was composed of two portions of different consistencies, one soft in the periphery and the other elastic and firm in the central portion. This tumor was grossly, totally removed. The patient made a full recovery and there was no recurrence 2 years and 9 months after operation. There have only been 7 previous case reports of spinal intramedullary gliofibroma. Gliofibroma is usually a relatively benign astroglial variant. Recognition of such a variant is clinically important in considering the extent of the operation and postoperative adjuvant therapy.
Calvarial Sclerosing Osteomyelitis
Authors: Klisch J. , Spreer J. , Bötefür I. , Gellrich N.-C. , Adler C.P. , Zentner J. , Schumacher M.
Published: April 2003

We report a 15-year-old boy who suffered from calvarial sclerosing osteomyelitis and presented with painful head swelling. X-rays of the skull revealed areas of irregular radiolucency. MR imaging and CT showed a well-demarcated intradiploic lesion with thickening of the skull extending from the frontal to the parietal calvarium with a low signal on T1-weighted images, strong but heterogeneous enhancement after gadolinium application and a mixed signal on T2-weighted images. Computer-navigated neurosurgery was planned, and the craniotomy defect was reconstructed by a preformed titanium implant. Sclerosing osteomyelitis of the calvarium has to be included in the differential diagnosis of osteolytic and sclerosing lesions of the skull coinciding with persistent swelling of the head.
Comparison of Motor Outcomes after Selective Dorsal Rhizotomy with and without Preoperative Intensified Physiotherapy in Children with Spastic Diplegic Cerebral Palsy
Authors: Steinbok Paul , McLeod Kimberley
Published: April 2003

A previous randomized clinical trial compared selective dorsal rhizotomy (SDR) plus postoperative intensified physiotherapy (group 1) with intensified physiotherapy alone (group 2) for children with spastic diplegic cerebral palsy. At the end of this trial, all patients in group 2 had an SDR, followed by further intensified physiotherapy. This study was performed to determine if the additional intensified physiotherapy before SDR, as occurred in group 2, improved long-term motor outcome. Outcomes were compared in the two groups, i.e. group 1 without intensified physiotherapy before SDR and group 2 with intensified physiotherapy before SDR. The primary outcome measure was the Gross Motor Function Measure (GMFM). Lower-limb spasticity, range and strength were secondary outcome measures. Baseline assessments had been done for the prior clinical trial. For this study, patients were reassessed by physiotherapists blinded to the treatment group. Thirteen children in each group were studied at a mean follow-up of 53 months. The mean improvement in GMFM was 10.0 in group 1 and 10.4 in group 2 (p = 0.9). Improvements in spasticity and range were similar in the two groups. There was no significant change in muscle strength in either group. It was concluded that in this relatively small series of patients, additional intensified physiotherapy before SDR did not improve motor outcomes.
Moyamoya Disease Associated with Hemophilia A
Authors: Matsuda Masahide , Enomoto Takao , Yanaka Kiyoyuki , Nose Tadao
Published: April 2003

A 10-year-old boy who had been diagnosed as having hemophilia A presented with episodes of transient ischemic attack. Cerebral angiography showed occlusions of the bilateral anterior cerebral arteries and the right middle cerebral artery with the development of an abnormal vascular network. The patient was diagnosed as having moyamoya disease associated with hemophilia A and subsequently underwent multiple burr hole surgery for revascularization under sufficient factor VIII supplementation. He remained asymptomatic after surgery, and follow-up cerebral angiography 5 months after the operation demonstrated significant neovascularization through the burr holes. Multiple burr hole surgery is proposed as a method of choice for the treatment of moyamoya disease associated with a bleeding tendency.
The Significance of Intrathecal Opioid Therapy for the Treatment of Neuropathic Cancer Pain Conditions
Authors: Becker R. , Jakob D. , Uhle E.-I. , Riegel T. , Bertalanffy H.
Published: April 2003

The effectiveness of intrathecal opioid therapy when applied to different pain mechanisms, in particular neuropathic and nociceptive pain conditions, was studied retrospectively in 43 patients suffering from cancer pain. On the basis of clinical and radiological data, the pain mechanisms were categorized as nociceptive (n = 23) and neuropathic (n = 20). The average duration of treatment of nociceptive pain was 5 months, of neuropathic pain only 2.5 months. The initial median reduction of pain with intrathecal opioid therapy was 77.8% for nociceptive and 61.1% for neuropathic pain. Long-term results with patients suffering nociceptive pain showed a continuing good median pain reduction of 66.7%. Patients suffering from neuropathic pain showed poor long-term results (11.1% median pain reduction). Neuropathic pain in the extremities reacted least to the application of intrathecal opioids. Optimal results were obtained for nociceptive pain in the trunk area of the body.
Brain Surgery with Image Guidance: Current Recommendations Based on a 20-Year Assessment
Authors: Lee John Y.K. , Lunsford L. Dade , Subach Brian R. , Jho Hae Dong , Bissonette David J. , Kondziolka Douglas
Published: April 2003

Image guidance promotes safe and effective surgical management of a wide array of intracranial diseases. To better define the historical importance of image guidance and to assess the relative contribution of each imaging modality to the safety and efficacy of selected procedures, we reviewed our 20-year experience at a single institution. A retrospective review of our departmental surgical records was performed to identify patients who underwent brain surgery with image guidance between January 1979 and January 1999. We identified the use of intraoperative fluoroscopy , endoscopy, computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and angiography in 7,388 patients. During this 20-year interval, advances in neuroimaging were translated into the operating room environment. Fluoroscopic guidance received the highest overall rating and was deemed critical for the performance of successful transsphenoidal surgery (n = 436) and effective percutaneous trigeminal neuralgia management (n = 1,121). Ultrasound and angiography both had limited roles; the latter was important to successful outcomes in 64 patients undergoing aneurysm management (n = 64) and arteriovenous malformation Gamma Knife radiosurgery (n = 786). Endoscopy also had a small role but had limited cost. Beginning in 1982, a dedicated operating room CT scanner was used during both morphologic and functional stereotactic surgery (n = 1,749). After 1986, MRI was used increasingly in the management of selected functional and tumor cases (n = 337); despite great versatility for patients undergoing Gamma Knife radiosurgery, the costs were relatively high. Frameless neuronavigation (n = 263) had excellent versatility and was relatively low in cost. During the last 20 years, image guidance techniques have facilitated minimally invasive brain surgery at our institution. The relative merits of all these imaging tools depended mostly on their versatility and relative costs. Major centers currently contemplating the incorporation of image guidance into routine brain surgery need not reproduce our own learning curve.
Prevention of Neurotoxin Damage of 6-OHDA to Dopaminergic Nigral Neuron by Subthalamic Nucleus Lesions
Authors: Chen Lin , Liu Zonghui , Tian Zengmin , Wang Yaqi , Li Shiyue
Published: April 2003

Object: To investigate the possibility that subthalamic nucleus (STN) ablation could prevent the toxicity of the selective dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA). Methods: Sixty rats were divided into 6 groups (n = 10). The control group received a unilateral microinjection of 6-OHDA into the right ventral tegmental area (VTA) and the right median forebrain bundle (MFB). Group 1 received an administration of kainic acid (KA) into the right STN and, 1-week later, an injection of 6-OHDA in the right VTA and MFB. Groups 2–5 received an injection of 6-OHDA in the right VTA and MFB, 1 h, 2 h, 3 days, and 7 days before KA in the right STN respectively. Four weeks later, the changes of tyrosine hydroxylase (TH)-positive (dopaminergic) neurons in the SNc were investigated with immunocytochemical and morphometrical methods. Results: The number of TH-positive cells in the SNc on the injected side of treated groups (groups 1–5) and control group were 71.46 ± 6.84, 57.07 ± 5.54, 51.09 ± 4.85, 12.68 ± 2.67, 4.15 ± 1.60 and 3.40 ± 1.54/slice, which decreased to 96.7, 72.9, 69.8, 17.2, 5.6 and 4.4% of the non-injected side, respectively. The number of TH-positive neurons in groups 1–4 significantly increased in comparison with the controls (p < 0.05, 0.01). In group 5, there were no remarkable differences in contrast to the number of TH-positive neurons of the controls (p > 0.05). The difference in the number of TH-positive neurons between groups 1–5 was statistically significant (p < 0.01). Conclusion: The results indicate that STN ablation can provide antiglutamate-based neuroprotection of the dopaminergic nigrostriatal pathway against 6-OHDA toxicity.
Improved Continence after Radical Retropubic Prostatectomy Using Two Pubo-Urethral Suspension Stitches
Authors: Campenni Michael A. , Harmon Justin D. , Ginsberg Phillip C. , Harkaway Richard C.
Published: April 2003

Objectives: To determine if placement of urethral suspension stitches during radical retropubic prostatectomy improves postoperative urinary continence. Methods: Between January 1997 and January 1998 we performed radical retropubic prostatectomy on 50 men. The first 25 consecutive men had their surgery without urethral suspension stitches while the next 25 received placement of two anastomotic urethral suspension stitches anchored to the lower portion of the pubic bone. Patients were interviewed six months postoperatively and each underwent valsalva leak-point pressure measurement. Patients were categorized as either completely continent (requiring no pads and having no measurable valsalva leak point), socially continent (zero or one pad per day), or incontinent (two or more pads per day). Results: In the urethral suspension group, 8/25 (32%) patients were completely continent and did not have a measurable valsalva leak-point pressure while 3/25 (12%) without urethral suspension were completely continent. Of the remaining patients in the urethral suspension group, 13/17 (76%) patients were socially continent while 4/17 (24%) were incontinent. The mean valsalva leak-point pressure in the 17 patients with suspension stitches was 89.6 ± 21.6 cm H2O. In the patients without urethral suspension, there were 22 patients who had some degree of incontinence. Among non-stitch patients, 13/22 (59%) were socially continent while 9/22 (41%) were incontinent. The average valsalva leak-point pressure in these patients was 74.0 ± 16.7 cm H2O, which was significantly lower than those with the suspension (p = 0.015). Conclusion: Placement of anastomotic urethral suspension stitches during radical retropubic prostatectomy may increase the likelihood of complete postoperative urinary continence. The urethral suspension stitches also increase valsalva leak-point pressure, which may improve the percentage of patients with socially acceptable incontinence.
Renal Metastasis from Squamous Cell Carcinoma of the Hypopharynx
Authors: Wada Takashi , Ichikawa Tetsuya , Okuzono Tatsuya , Okuzono Yoshiko , Naito Katsusuke
Published: April 2003

We present a rare case of metastatic renal tumor originating from squamous cell carcinoma of the hypopharynx. A 67-year-old man treated with irradiation for hypopharyngeal carcinoma was referred to our hospital with gross hematuria and a left renal mass, which was delineated as a heterogeneously enhanced mass by CT scan. Left nephrectomy was performed, and the non-encapsulated mass was gray in color macroscopically. Histological examination of the specimen revealed alveolar proliferation of small cancer cells, which was consistent with the original tumor of the hypopharynx. The left renal tumor was diagnosed as poorly differentiated squamous cell carcinoma metastasized from the hypopharynx. The patient remains alive, with no evidence of disease, 8 months following left nephrectomy. This case was thought to be the first report of a renal metastasis from a hypopharyngeal carcinoma that was diagnosed clinically and treated with nephrectomy.
Opsoclonus-Myoclonus Syndrome as a Paraneoplastic Manifestation of Renal Cell Carcinoma
Authors: De Luca S. , Terrone C. , Crivellaro S. , De Zan A. , Polo P. , Vigliani M.C. , Tizzani A.
Published: April 2003

Opsoclonus is a rare but distinctive disorder of ocular motility, characterized by irregular, continual and conjugated chaotic saccades of the eyes. It is increased with eye closure and fixation, and it persists during sleep. Opsoclonus appears more commonly in children and in half of such cases in association with neuroblastoma. In adults the most frequent causes are idiopathic (50%) and paraneoplastic (20%). Among the second group, different types of tumors involving a wide variety of organs have been reported. Opsoclonus when accompanied by other symptoms of central nervous system involvement (head, appendicular myoclonus and truncal ataxia) constitutes a clinical picture, known as opsoclonus-myoclonus syndrome. We report the case of a young patient affected by renal cell carcinoma associated with opsoclonus-myoclonus syndrome which did not respond to medical therapy but dramatically improved after cancer ablation.
Combination Cefixime/Amoxicillin against Penicillin-Resistant Streptococcus pneumoniae Infection
Authors: Matsumoto Yoshimi
Published: April 2003

The rising incidence of antibiotic resistance, including penicillin-resistant Streptococcus pneumoniae (PRSP), has become a great clinical problem in many countries. Cefixime, an orally active third-generation cephalosporin has broad and potent activity against various pathogens, especially gram-negative organisms including beta-lactamase producing strains. However, as with all other oral agents, cefixime is inactive against PRSP. As a possible solution to this problem, the effectiveness of a combination of cefixime and amoxicillin which retains stronger activity against PRSP was evaluated. This combination worked synergistically against S. pneumoniae including PRSP by the checkerboard method with a mean FIC index value of 0.60 and the time-kill kinetic method. Similarly, a synergistic effect was shown in the mouse respiratory tract infection model, with an FED index of 0.29 (cefixime:amoxicillin = 2:1). Additionally, this combination showed excellent activity against mixed organisms including PRSP, in the human serum level simulating kinetic method and mouse respiratory mixed infection models. We review here briefly preclinical studies carried out in our laboratory which demonstrate the synergistic effect of this cefixime plus amoxicillin combination, and suggest the empirical therapeutic potency of this combination for treating community-acquired respiratory tract infections, including PRSP, in the clinical setting.
Amphotericin B Colloidal Dispersion
Authors: Working P.K.
Published: April 2003

Amphotericin B Colloidal Dispersion (ABCD, AmphocilTM), a noncovalent complex of amphotericin B and cholesteryl sulfate, is active in vitro and in vivo against a wide variety of fungal species; its activity is broadly comparable to the range of activity of conventionally formulated amphotericin B (CAB). The pharmacokinetics of ABCD and CAB differ. ABCD is more rapidly removed from circulation than CAB, with more than 99% clearance one hour after administration, but has a much more prolonged terminal elimination phase. Preclinical safety studies have shown that ABCD is significantly better tolerated and less nephrotoxic than CAB. ABCD does cause renal tubular damage after high doses, but only at doses five- to eight-fold higher than those of CAB. Preclinical studies suggest that the efficacy, but not the toxicity of ABCD and CAB will be identical. ABCD may thus provide a safer therapeutic alternative to CAB.
Clinical Efficacy of Amphotericin B Colloidal Dispersion against Infections Caused by Aspergillus spp
Authors: Gurwith M.
Published: April 2003

Three published clinical trials of the efficacy of amphotericin B colloidal dispersion (ABCD) against infections caused by Aspergillus spp were reviewed. A total of 376 patients was treated. Systemic aspergillosis was identified in 67 evaluable patients. Overall, a complete or partial response was achieved in 47.8% of the evaluable patients, although there were substantial differences in the response rates between studies. Reasons for recruitment caused a marked difference in response rates. The overall response rate for ABCD in patients in which conventional amphotericin B (CAB) was contra-indicated or had previously failed was 34.3%, whereas the response rate in bone marrow transplant (BMT) or patients with renal impairment was 57.9 and 62.5% respectively. The efficacy of ABCD at doses of 4 mg/kg/day appears to be at least as good as in studies using CAB. The levels of renal toxicity were low at a dose of 4 mg/kg/day. Dose-limiting studies indicate that dosages can be safely increased to 7.5 mg/kg/day creating opportunity for improved efficacy.
Safety and Efficacy of Amphotericin B Colloidal Dispersion
Authors: Herbrecht R. , Letscher V. , Andres E. , Cavalier A.
Published: April 2003

The efficacy and safety of Amphotericin B Colloidal Dispersion (ABCD) have been investigated on 572 patients in five Phase I/II clinical trials. The patients were all selected to present a challenging test; having a fungal infection superimposed on severe illness. In 442 cases ABCD was used after amphotericin B, which had been withdrawn. One hundred and forty patients had pre-existing nephrotoxicity. Most patients received doses of 3–6 mg/kg/day of ABCD. Complete or partial recovery was reported in 149/260 (57.3%) patients evaluable for therapeutic response. Patients with Candida infection responded better than those with systemic aspergillosis showing 70.1% recovery vs. 48.8%. ABCD therapy made no difference to serum creatinine levels, even in patients with pre-existing renal failure, nor to liver function as measured by SGOT, alkaline phosphatase and total bilirubin levels in serum. Infusion-related adverse events were the most frequently reported side effects of ABCD. However these studies show clearly that ABCD can be administered safely to patients without the risks of renal toxicity, even when renal toxicity had already developed following therapy with conventional amphotericin B deoxycholate.
Quinolones and Multidrug-Resistant Tuberculosis
Authors: Maranetra Khun Nanta
Published: April 2003

The prevalence of initial resistance of multidrug-resistant tuberculosis (MDR-TB) to at least isoniazid (INH) and rifampicin (RFP) in Thailand during the period 1993–1997 is reported; in this era, trends for INH + RFP + streptomycin (SM) and ethambutol (EMB), INH + RFP + SM or EMB and MDR-TB were stable. The prevalence of acquired MDR-TB is on a slight downward trend, with the latest level at 22.6%. Recommended management of MDR-TB is outlined and advantages and disadvantages of these guidelines discussed. The role of ofloxacin in MDR-TB is presented, with results from a study performed by the Thailand CDC showing that the percentage of strains resistant to ofloxacin was 4.3%, and to ciprofloxacin was 8.3%. The resistance to both ofloxacin and ciprofloxacin was very low at 1.4%. The percentage of cross-resistance between these fluoroquinolones was also low; 33% resistant to ofloxacin were also resistant to ciprofloxacin and only 17% of those resistant to ciprofloxacin were also resistant to ofloxacin. Results from a clinical trial evaluating ofloxacin with other drugs for MDR-TB are also reported. The regimen comprised ofloxacin 600 mg/day, pyrazinamide (PZA), two to three months of kanamycin (KM) or amikacin (AMK), para-aminosalicylic acid (PAS) plus EMB or thiacetazone. Drugs were given for 18 months. Follow-up was every three months for two years. Preliminary results revealed that the percentage of acquired MDR-TB resistant to specific agents was as follows: 36% resistant to INH and RFP, 23% resistant to INH, RFP plus EMB, 27% resistant to INH, RFP and SM, and 14% resistant to all four of these agents (INH + RFP + SM + EMB). All isolates were sensitive to ofloxacin. At one month of treatment, sputum culture conversion was approximately 25%, climbing to 93% by nine months of treatment. Treatment with ofloxacin in a combined regimen achieved a success rate of 78%. The role of quinolones in preventing TB in MDR-TB contacts is also discussed.
Antimicrobial Resistance in Respiratory Tract Pathogens: Results of an International Surveillance Study
Authors: Thornsberry Clyde , Sahm D.F.
Published: April 2003

An international surveillance study was performed to assess the resistance patterns among respiratory tract pathogens during the winter of 1997–1998. The pathogens studied included Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. The antibiotics tested included five β-lactams (penicillin, ampicillin, amoxicillin, amoxicillin-clavulanic acid, cefuroxime axetil and ceftriaxone), two macrolides (azithromycin and clarithromycin), one sulfonamide (trimethoprim-sulfamethoxazole), one glycopeptide (vancomycin) and one fluoroquinolone (levofloxacin). A total of 11,502 isolates were tested from nine countries, using microdilution susceptibility tests as recommended by National Committee for Clinical Laboratory Standards (NCCLS) guidelines. The susceptibility rates varied greatly around the world. Ninety percent of M. catarrhalis isolates produced β-lactamase, making them resistant to ampicillin. β-Lactamase production by H. influenzae ranged from 5% in Germany to 34% in the USA (mean 17.5%). Of the S. pneumoniae isolates, 32.8% had some resistance to penicillin, but this ranged greatly from 7.8% in Germany to 66.5% in France. Penicillin resistance in S. pneumoniae was associated with resistance to other β-lactams, macrolides and sulfonamides, but not to levofloxacin or vancomycin. All isolates of H. influenzae and M. catarrhalis were susceptible to levofloxacin. Results of this study support the conclusion that these three respiratory tract pathogens are becoming more resistant to selected antimicrobials, and that the level of resistance in these isolates to the antimicrobials varies greatly from one country to another.
A 13-Year Study of Antimicrobial Susceptibility of Common Gram-Negative Bacteria Isolated from the Bloodstream in a Teaching Hospital
Authors: Ling Thomas K.W. , Ling Thomas K.W. , Liu Esther Y.M. , Liu Esther Y.M. , Cheng Augustine F.B. , Cheng Augustine F.B.
Published: April 2003

The choice of antimicrobial therapy for the treatment of bacteremia is often empirical and based on the knowledge of susceptibility profiles of the most common bacteria. We analyzed blood culture isolates from a teaching hospital for 13 years prospectively. This study examined the susceptibility profiles of 6,616 gram-negative bacteria. Escherichia coli ranked among the commonest bacteria, representing 43.6% (2,890) of all gram-negative isolates. Klebsiella sp. ranked second, 17.7% (1,171) and 16.7% were resistant to ceftazidime in 1997. There was a trend towards an increase in resistance to fluoroquinolones in the common gram-negative bacteria. Imipenem was the most active agent against gram-negative bacteria. The results of the susceptibility of gram-negative bacteria causing bacteremia provide valuable information for implementing the appropriate chemotherapy for bacteremia.