bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Artificial Tears on Corneal Surface Regularity in Patients with Sjögren Syndrome
Authors: Iskeleli Güzin , Kizilkaya Melda , Arslan Osman S. , Ozkan Sehirbay
Published: April 2003

Purpose: To evaluate the effect of artificial tears on the topographic parameters associated with corneal surface regularity in patients with Sjögren syndrome. Methods: A total of 38 eyes of 20 patients with Sjögren syndrome were evaluated prospectively. The mean age of the patients was 50.5 ± 15.3 years (range, 28–76). Corneal topography with the Topographic Modeling System (TMS-2, Tomey) was performed before and after the instillation of artificial tears. The surface regularity index (SRI), surface asymmetry index (SAI), potential visual acuity (PVA) and mean astigmatism were compared in dry eyes before and after the instillation of artificial tears. Results: Before the instillation of artificial tears SAI, SRI, PVA and mean antigmatism values were found to be 1.37 ± 1.47, 0.74 ± 0.42, 20/30.92 ± 20/8.12 and 1.53 ± 1.47 D, respectively. In corneal topography performed after the instillation of artificial tears SAI, SRI, PVA and mean astigmatism values were 0.71 ± 0.82, 0.43 ± 0.36, 20/25.92 ± 20/5.55 and 1.08 ± 1.18, respectively. When compared statistically, the SRI, SAI, and mean astigmatism all decreased significantly and the PVA improved (p = 0.0001). Conclusion: Irregular corneal surface in dry eye patients affects optical quality. The statistically significant improvement observed in SRI and SAI values after the instillation of artificial tears also improves the PVA that is especially related to SRI.
Sex Ratios in Congenital Malformations of the Central Nervous System
Authors: Lemire Ronald J. , Pendergrass Thomas W.
Published: April 2003

Malformations of the central nervous system (CNS) are evaluated and treated by pediatric neurosurgeons. There is a spectrum of morphological variations within each type of malformation and with associated features that may determine whether the defect is isolated or part of a syndrome. Alterations in the normal sex ratio have been found in many malformations of the CNS but the reasons for them are usually unclear. It can be reasoned that some CNS malformations would have unusual sex ratios by chance alone. However there are recurrent patterns. When there is a dominance of one sex for a particular malformation, this information can help predict the likelihood of the malformation in a patient and influence diagnostic approaches. The present report provides information on selected CNS malformations that have altered sex ratios.
Limited Dorsal Myeloschisis Associated with Multiple Vertebral Segmentation Disorder
Authors: Isono Mitsuo , Goda Makoto , Kamida Tohru , Ishii Keisuke , Kobayashi Hidenori , Maeda Tomomi , Imai Kazuhide , Izumi Tatsuro
Published: April 2003

A 3-year-old girl was admitted to our department with spina bifida occulta. At birth, thoracic dysplasia with severe respiratory dysfunction and a soft pedunculated mass connecting with an intradural mass were noted. The patient did not start to walk and partial removal of the intradural mass was performed via a laminectomy of the fused vertebrae. There was no boundary between the spinal cord and the mass and the histological diagnosis of this mass was connective tissue. The anomalies in this case were considered to be multiple vertebral segmentation disorder (MVSD) and limited dorsal myeloschisis. The coincidence of these anomalies might suggest the causal genesis of MVSD.
Cervical Hematomyelia: A Rare Entity in a Neonate with Cesarean Section and Surgical Recovery
Authors: Önal Çagatay , Yakinci Cengiz , Kocak Ayhan , Erguvan Rezzan , Tekiner Ayhan , Kutlu Ramazan , Özcan Cemal , Gul Abdulkadir
Published: April 2003

Spinal cord injury with or without trauma has been reported in the perinatal period. The prognosis depends primarily on diagnosis of the level, extent and nature of the lesion, established by correlations between clinical, imaging and electrophysiological data. A 25-day-old boy with normal birth weight delivered at term by cesarean section was transferred to Inönü University Turgut Özal Medical Center because of respiratory distress and brachial diplegia. A suspicious medullary lesion on cervical computerized tomography was confirmed as an intramedullary lesion extending from C3 to D1 on magnetic resonance imaging (MRI). Emergent surgery consisting of exposure of the lesion site and interlaminar direct puncture of the lesion under fluoroscopy revealed that the pathology was an intramedullary hematoma. The partial evacuation of the lesion with direct puncture, the patient’s neurological improvement and close follow-up of the patient with ultrasonography, electrophysiology and MRI are discussed in the light of recent literature.
Growing Fractures of the Orbital Roof
Authors: Suri A. , Mahapatra A.K.
Published: April 2003

Growing fractures rarely arise in the skull base. Only six cases of orbital roof growing fractures were found in the relevant literature. We report two such cases. The first case was a 2-year-old girl who had progressive proptosis for 6 months following a mild head injury 1 year previously. The second case was a 9-year-old girl with a history of injury at the age of 3 months. She developed eye deviation and proptosis for 1 year. Computed tomography scan is excellent for demonstrating bony defects in the orbital roof, while magnetic resonance imaging is more sensitive in showing the intraorbital extension of a leptomeningeal cyst. Both patients were operated successfully and proptosis disappeared postoperatively. The exact pathophysiology of growing fractures is still debated in the literature, but a dural laceration along a fracture line is noted in all cases, and frontobasal brain injury seems to play an important role in the pathogenesis of the fracture growth. Growing fractures of the orbital roof should be suspected if ocular symptoms appear in a child who had sustained a head injury several months or years before.
Anterior Encephaloceles: A Study of 92 Cases
Authors: Mahapatra A.K. , Suri A.
Published: April 2003

Anterior encephalocele is a rare condition, and only a few large series have been published in the literature. Surprisingly, the incidence is much higher in Southeast Asian countries, including some parts of India. While the reported incidence in the West is between 1:35,000 and 1:40,000 live births, it is as high as 1:5,000 live births in Thailand. We present a series comprising 92 cases of anterior encephaloceles treated over a 30-year period (1971–2000). Frontoethmoidal encephaloceles are the commonest type, followed by the nasopharyngeal and orbital type. Among the frontoethmoidal encephaloceles, nasoethmoid is the commonest type, and these patients present with swelling over the bridge of the nose with significant hypertelorism and orbital deformities. The nasopharyngeal type remains occult and presents with nasal obstruction or CSF rhinorrhea. Rarely, the patient may present with meningitis. Since 1978, computed tomography (CT) scans have regularly been performed in our patients. CT scans delineate the skull defect and associated brain anomalies. There was associated hydrocephalus present in 12 patients and agenesis of the corpus callosum in 5 patients. In all patients, one-stage repair of the encephalocele and correction of bony anomalies by appropriate osteotomy was undertaken. Since 1988, in cases of frontoethmoidal encephalocele with significant hypertelorism, medial advancement of the medial half of the orbits on either sides was carried out, instead of a classical Tessier’s operation. Postoperative morbidity included CSF leak in 20 patients, wound infection in 2 and chest infection in 3. There were 3 deaths in our study. The overall cosmetic outcome was good.
Choroid Plexectomy Reduces Neurosurgical Intervention in Patients with Hydranencephaly
Authors: Wellons III John C. , Tubbs R. Shane , Leveque Jean-Christophe A. , Blount Jeffrey P. , Oakes W. Jerry
Published: April 2003

Introduction: The removal of the choroid plexus from the lateral ventricles was attempted by Dandy in the early 20th century but later discarded as complications arose and other methods of cerebrospinal fluid (CSF) diversion were introduced. We compare our experience with a variation of this operation to CSF diversion in patients with hydranencephaly or near hydranencephaly. Methods: The hospital and office charts of patients with a diagnosis of hydranencephaly were reviewed from the two institutions spanning the career of the senior author. Thirteen patients were identified, of whom 9 underwent CSF diversionary procedures (group A) and 4 underwent choroid plexectomy (group B). Results: The mean number of reoperations (2 in group A, 0 in group B), neurosurgical readmissions (1.5 in group A, 0 in group B) and days of hospitalization related to neurosurgical readmissions (43.5 in group A, 0 in group B) were all less in patients who underwent choroid plexectomy. The total incidence of complications related to surgery was also lower in this group (7 in group A, 0 in group B). Conclusion: In our experience, choroid plexectomy in patients with hydranencephaly reduces the incidence of reoperation and readmission, the number of days of hospitalization related to the surgical procedure and the total number of complications in comparison to patients undergoing CSF diversion. Further neurosurgical intervention is minimized as is the financial burden from multiple emergency department visits and radiological procedures for shunt evaluation. Choroid plexectomy is a viable alternative to CSF diversion in patients with hydranencephaly and a rapidly enlarging head. It avoids the chronic issues and complications surrounding CSF diversion in this difficult group of patients.
Interscapular Placement of a Vagal Nerve Stimulator Pulse Generator for Prevention of Wound Tampering
Authors: Le Hoang , Chico Maria , Hecox Kurt , Frim David
Published: April 2003

In some cognitively delayed children who require a vagal nerve stimulator for treatment of their seizures, there is a risk of wound breakdown and infection from obsessive tampering with the wound. We describe the interscapular placement of the vagal nerve stimulator pulse generator as a method to reduce this risk.
Quantitative On-Line Analysis of Physiological Data for Lesion Placement in Pallidotomy
Authors: Lehman Richard M. , Micheli-Tzanakou Evangelia , Medl Attila , Hamilton Jennifer L.
Published: April 2003

A computerized method of determining the focal point of electrical activity in the pallidum of parkinsonian patients was developed using on-line quantitative physiological data analysis. Thirty patients in a series of 70 were studied in depth. Neuronal activity was recorded from the pallidum using a semi-microelectrode. The signal is inspected visually while its average power, characteristic frequency and complexity are computed. The target locus was indicated by the highest level of global activity in the vicinity of the electrode (signal power maximum), maximal signal complexity and minimal characteristic frequency. Most often, the vertical coordinate required correction. The postoperative clinical and imaging results have indicated the effectiveness of this method.
Combined Treatment Effects after Embolization and Radiosurgery in High-Grade Arteriovenous Malformations
Authors: Duffner Frank , Freudenstein Dirk , Becker Gerd , Ernemann Ulrike , Grote Ernst H.
Published: April 2003

In recent years the multimodal therapy concept has been established for high-grade intracerebral arteriovenous malformations (AVM). One strategy of a multimodal treatment approach for patients with AVM (Spetzler grade V) is reported. After endovascular embolization, the patient underwent radiosurgical treatment of the remaining nidus with a linear accelerator, after which he developed a left-sided hemiparesis in conjunction with severe edema. Angiographic control 44 months after radiation showed an occlusion of the radiosurgically treated nidus. The remaining nidus could be removed by microsurgery. The combination of embolization and radiosurgery may provoke prolonged edema and permanent neurological deficits due to inflammatory perivascular changes.
Use of Selective Thalamotomy for Various Kinds of Movement Disorder, Based on Basic Studies
Authors: Ohye Chihiro
Published: April 2003

Methods of selective thalamotomy with microrecording for several kinds of movement disorder are described. Precise thalamotomy (Vim, VO or Vim+VO) depends on the understanding of the functional organization of the human thalamus on the one hand, and the patient’s specific feature of movement disorders on the other. To realize selective thalamotomy, microrecording and a computerized planning system are essential. Thus, a properly selected thalamotomy for movement disorders is quite useful.
The Surgical Treatment of Intractable Epilepsy
Authors: Liu Zonghui
Published: April 2003

The author reviewed the various surgical approaches for intractable epilepsy and proposes that any surgical operation for the treatment of intractable epilepsy be performed actively but prudently. It is important to identify the operation indication and to use combinations of anterior callosotomy, epileptogenic focus resection and multiple subpial transection (MST), tailored to the individual patient. Selective temporal lobe removal can also provide a fairly good result in temporal lobe seizures. For epileptogenic foci in functional areas, MST was an effective approach that protected neural function and blocked epileptic discharge. For epileptogenic foci in the free-functional areas, however, epileptogenic focus resection was still the best therapy. Hemisphere removal should be chosen cautiously and only for patients with intractable epilepsy with progressive neurological deficits in the hemisphere. The author notes that using minimally invasive neurosurgery techniques to treat epilepsy and to protect neural function will become more widely recommended.
Selective Denervation and Resection of Cervical Muscles in the Treatment of Spasmodic Torticollis: Long-Term Follow-Up Results in 207 Cases
Authors: Chen Xinkang , Ma Anbao , Liang Jian , Ji Shaoxian , Pei Shengua
Published: April 2003

Object: To report the outcome of patients with selective denervation and resection of cervical muscles for spasmodic torticollis. Methods: We reviewed 362 cases of surgically treated spasmodic torticollis. 207 patients were followed from 2 years to 29 years. Results: Total or marked relief of symptoms with preservation of normal of nearly normal movements has been obtained in 87.9%. Conclusion: This procedure may be recommended if one to two years of conservative therapy does not offer satisfactory relief of symptoms.
Stereotactic Biopsy for Intracranial Space-Occupying Lesions: Clinical Analysis of 550 Cases
Authors: Yu Xin , Liu Zonghui , Tian Zengmin , Li Shiyue , Huang Hongyun , Xiu Bo , Zhao Quanjun , Liu Linlin , Jing Wenji
Published: April 2003

Object: To investigate the role of stereotactic biopsy in planning the optimal management of intracranial space-occupying lesions. Patients and Methods: Between December 1989 and December 1999, stereotactic biopsy was performed in 550 patients with intracranial mass lesions that were deep-seated or located in the functional area. There were 340 males and 210 females, and their ages ranged from 4 to 75 years. All the procedures were done under local anesthesia with a Leksell stereotactic system. A CT scan was used to determine the coordinates in the first 420 cases and the Aero Tech Stereotactic Surgical Plan System in the subsequent 130 patients. Results: Brain tumors were diagnosed pathologically in 475 patients (86.4%), inflammatory process in 44 (8.0%), other lesions in 12 (2.2%) and no conclusive diagnosis was found in 19 (3.4%). The overall positive rate of biopsy was 96.6%, and the positive rate for brain tumor was 86.4%. Intracranial hematomas after biopsy were found in 13 cases (2.4%). Seizures occurred during the operation in 7 cases (1.2%), and slight and transient neurological deficits were found in 23 cases (4.2%). There were no deaths or other serious complications. Conclusions: The results suggest that the stereotactic biopsy is a reliable method to obtain histopathological diagnosis of intracranial mass lesions, and it is also of great help in selecting the appropriate management.
Combined Treatment with Stereotactic Intracavitary Irradiation and Gamma Knife Surgery for Craniopharyngiomas
Authors: Yu Xin , Liu Zonghui , Li Shiyue
Published: April 2003

Object: To evaluate the effectiveness of the combined treatment of stereotactic intracavitary irradiation and Gamma Knife surgery on craniopharyngiomas. Patients and Methods: Combined treatment with stereotactic instillation of radioisotopes and Gamma Knife surgery was performed on 46 patients with craniopharyngioma between October 1996 and June 1999. There were 13 solid tumors and 33 mixed solid and cystic tumors. Results: 38 patients (10 solid and 28 mixed) were followed up from 6 months to two years. The tumor control rate was 90% in solid tumors, 85.7% in mixed tumors, 92.1% in the solid segment and 89.5% in total. Conclusions: Gamma Knife surgery plays an important role in the treatment of the solid component of craniopharyngiomas and the combination of treatment is a simple, safe and effective method for treatment of craniopharyngiomas, especially for the recurrent mixed solid and cystic tumors.
Analysis of Related Factors in Complications of Stereotactic Radiosurgery in Intracranial Tumors
Authors: Liu Yuanzhao , Xiao Shuhua , Liu Mingyuan , Li Gaofen , Wang Dechang , He Jingxue , Hu Bing , Zu Defa
Published: April 2003

Object:To investigate the related factors in complications of stereotactic radiosurgery for intracranial tumors. Methods: A retrospectective review of 146 patients with intracranial tumors treated with stereotactic radiosurgery was conducted. Sixty-five patients received single-dose treatment and the rest received fractionated stereotactic radiosurgery. Ninety-five patients received conventional radiotherapy in the meantime. Results: Follow-up period was 18–54 months. Follow-up rate was 92.5% and 39 patients (26.7%) had different complications. The Cox statistics showed that target volume, target peripheral dose, target maximal dose, and ratio of maximal dose to peripheral dose are related to the complications. Conversely, neither type of tumor disease, gender, radiation schedule with or without conventional radiotherapy, target minimal dose, nor ratio of target peripheral isodose volume to target volume were found to be related to complications. Conclusion: Target volume and dose are the major factors causing complications, and the optimization of the therapeutic planning can play a significant role in reducing them.
Ipsilateral Thalamic Stimulation after Thalamotomy for Essential Tremor
Authors: Racette Brad A. , Rich Keith M. , Randle Jennifer , Mink Jonathan W.
Published: April 2003

We report a patient with severe essential tremor who was treated with thalamic stimulation ipsilateral to a prior thalamotomy. Thalamotomy performed 30 years prior to stimulator implantation provided tremor reduction for one year before the tremor recurred. An electrode lead was implanted in the thalmaic nucleus ventralis intermedius (Vim) with nearly complete control of his tremor with sustained benefit over an 18-month follow-up period. Vim thalamic stimulation is an effective treatment option for recurrent tremor in patients who have undergone ipsilateral thalamotomy.
Femoral Nerve Palsy Caused by a Self-Retaining Polyretractor during Major Pelvic Surgery
Authors: Corbu Carlo , Campodonico Fabio , Traverso Paolo , Carmignani Giorgio
Published: April 2003

Postoperative femoral neuropathy is not a well-recognized complication in urology. We report 2 cases of femoral nerve palsy due to compression ascribed to the use of the self-retaining retractor. In the first case, the left femoral nerve was injured, and in the second case nerve injury was bilateral and synchronous. The clinical symptoms were a weakness of the quadriceps muscle and sensory anesthesia of the surrounding skin.
New Perspectives Offered by a French Study of Antibiotic Resistance in Day-Care Centers
Authors: Dellamonica Pierre , Pradier Christian , Dunais Brigitte , Carsenti Hélène
Published: April 2003

To provide ongoing information on regional trends of antibiotic resistance prevalence to pneumococci, a cross-sectional survey was conducted on a large representative sample of children attending day-care centers. Children were analyzed in spring (n = 379) and autumn (n = 379) for nasopharyngeal carriage. Streptococcus pneumoniae was detected in 149 children (39.4%) in spring and 204 (59.8%) in autumn. Half of these isolated strains showed penicillin insensitivity or resistance. A high proportion of children (43.6% in spring and 47.5% in autumn) had been treated with antibiotics during the 3 months prior to sample collection; 21.6% of isolated strains were serotype 6B, 20.1% type 23F, 18.9% type 19A and 19F, 11.5% type 14. Reduced susceptibility was frequently noted in serotype 23F, 14 and 9V, representing 93, 94 and 83% of identified serotypes, respectively. This type of survey on children in day-care centers can contribute to the understanding of regional variations in antibiotic resistance and provide information for epidemiological surveillance.
Cefixime in the Treatment of Upper Respiratory Tract Infections and Otitis media
Authors: de Lalla Fausto
Published: April 2003

An increasing number of clinical failures has been noted after treatment of upper respiratory tract infection and acute otitis media with conventional antibiotics. At present, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and group A beta-hemolytic streptococcus (GABHS) are the bacterial pathogens most frequently responsible for these infections. Although GABHS has so far not developed penicillin resistance, the frequency of bacteriological failures with either benzathine penicillin or penicillin V has increased. Firstly, a number of hypotheses have been put forward to explain this, including poor patient compliance and inactivation by beta-lactamase-producing oropharyngeal flora. Secondly, this has added to the demand for new agents to treat resistant streptococci. Cefixime, an orally active third-generation cephalosporin, has attracted considerable attention following the results of numerous clinical studies. Comparative studies between cefixime and conventional antibiotics for the treatment of upper respiratory tract infections and otitis media are summarized.
Treatment of Visceral Leishmaniasis with Amphotericin B Colloidal Dispersion
Authors: Berman J. , Dietze R.
Published: April 2003

Amphotericin B is an effective antileishmanial agent whose use is limited by drug toxicity. The development of less toxic, lipid encapsulated formulations of amphotericin B as antimycotic agents has made these formulations available for testing against visceral leishmaniasis, a disease ideally suited for ‘liposomal’ therapy since the parasites are only found within reticuloendothelial macrophages. In phase II experiments of Amphotericin B Colloidal Dispersion (ABCD) for Brazilian kala-azar, 10 of 10 patients were cured with 2 mg/kg/day for 10 days; 9 of 9 patients were cured with 2 mg/kg/day for 7 days; 9 of 10 patients were cured with 2 mg/kg/day for 5 days. The ability to cure 90% of kala-azar patients with a regimen of merely 5 days is remarkable considering that 20–40 days of treatment with pentavalent antimonials and a 28–40 day course of (every-other-day) amphotericin B desoxycholate therapy are otherwise needed. Although ABCD did frequently cause a syndrome of fever and respiratory distress during infusion for children less than 6 years of age, the virtual absence of kidney toxicity was striking.
Efficacy of Low-Dose Ofloxacin in the Treatment of Multidrug-Resistant Tuberculosis in Indonesia
Authors: Mangunnegoro Hadiarto , Hudoyo Achmad
Published: April 2003

There is growing concern, even among developed countries, about the increasing incidence of tuberculosis that is resistant to both isoniazid and rifampicin. Results are reported herein from a study investigating ofloxacin in the treatment of 58 patients with multidrug-resistant tuberculosis (MDR-TB). Patients received ofloxacin 400 mg/day accompanied by three other anti-TB drugs to which there was in vitro susceptibility. Treatment duration was nine months. Of 50 evaluable patients, our results showed that bacterial conversion as assessed by sputum microscopy occurred in 23 patients (46%) at three months of therapy, in 36 (72%) at six months, and in 39 (78%) at the end of nine months of therapy. Culture negativity was found in 36 patients (72%) at nine months of therapy. Relapses occurred in four of 36 patients (11%) who achieved culture negativity at the end of the treatment period. Ofloxacin 400 mg in combination with other active anti-TB medications shows promising results in the treatment of MDR-TB in Indonesian patients.
Treatment of Community-Acquired Pneumonia
Authors: Bartlett John
Published: April 2003

Lower respiratory tract infections are the major cause of death due to infectious disease in the developed and developing world. Despite substantial progress in defining pathogens and in therapeutic options, there continues to be major controversies in the clinical management of these infections. This report reviews the guidelines for community-acquired pneumonia from the Infectious Diseases Society of America (IDSA), updated from the initial publication. Diagnosis should include a chest X-ray to differentiate acute bronchitis from pneumonia. The decision for hospitalization should be based on social factors and evaluation of severity of illness. Identification of an etiological agent for inpatients should include two pretreatment cultures, one pretreatment sputum specimen, with seriously ill patients requiring studies for Legionella spp. Recommendations for empiric treatment of outpatients are doxycycline, a macrolide or a fluoroquinolone. Recommendations for empiric treatment of hospitalized patients are a cephalosporin plus a macrolide, or a fluoroquinolone alone. Recommendations for ICU patients are a β-lactam combined with either a macrolide or a fluoroquinolone. While concern has arisen about increasing resistance to fluoroquinolones, arguments in favor of these agents include the fact that they have good in vitro activity against nearly all treatable pathogens except some anaerobes. Clinical trials have shown equivalence or superiority compared to other standard agents. They are well tolerated, and can be administered intravenously or orally, once daily. A recent retrospective review has shown superior outcome with fluoroquinolone treatment compared to cephalosporins, including a 36% reduction in mortality.
Penetration of Minocycline Hydrochloride into Lung Tissue and Sputum
Authors: Watanabe Akira , Watanabe Akira , Anzai Yoshiyuki , Anzai Yoshiyuki , Niitsuma Katsunao , Niitsuma Katsunao , Saito Miwako , Saito Miwako , Yanase Kenji , Yanase Kenji , Nakamura Mikae , Nakamura Mikae
Published: April 2003

Penetration of minocycline hydrochloride (MINO) into lung tissue and sputum was investigated. MINO (100 mg) was intravenously infused over 30 min to 14 patients before lung surgery: the concentration of MINO was determined in 16 lung tissue samples which were collected between 0.25 and 5.0 h after infusion. The mean concentration of MINO in lung tissue sample was 2.92 ± 1.43 µg/g, and the mean lung tissue/plasma ratio of MINO concentration was 3.71 ± 2.36. MINO was infused intravenously over 60 min twice daily to 5 patients with a chronic respiratory disease for 3–7 days. The concentration of MINO in sputum and in serum was determined on day 3. The mean maximum concentration of MINO in sputum sample was 2.12 ± 2.20 µg/g, and the mean sputum/serum ratio of MINO concentration was 0.56 ± 0.47. The concentration of MINO in sputum showed little time-related variation and remained as high as 0.74 µg/g until 10 h after infusion. The concentration of MINO in sputum and in serum after intravenous drip infusion was about twice as high as that after oral administration at the same dose. The breakpoint was 1.88 for MINO, as calculated by the formula established by the Japan Society of Chemotherapy.
In vitro Susceptibility to Everninomycin of Gram-Positive Nosocomial Pathogens Isolated from Intensive Care Units in Germany
Authors: Kropec Andrea , Kropec Andrea , Frank Uwe , Frank Uwe , Jonas Daniel , Jonas Daniel , Thriene Wolfgang , Thriene Wolfgang , Schmidt-Eisenlohr Elke , Schmidt-Eisenlohr Elke , Daschner Franz Dieter , Daschner Franz Dieter
Published: April 2003

Background: Gram-positive bacteria are increasingly found to be causative pathogens in nosocomial infections, and the occurrence of vancomycin resistance in enterococci as well as staphylococci has prompted the investigation of alternative antimicrobial agents active against these strains. Everninomycin, a new oligosaccharide antibiotic, has excellent in vitro activity against gram-positive bacteria, including those resistant to vancomycin. However, avilamycin, a related compound, has been used in Europe as a growth promoter in animal food for years and concern has been raised that cross-resistance in clinical isolates may arise. Methods: We studied a collection of 268 nosocomial gram-positive isolates from intensive care unit patients with nosocomial pneumonia, urinary tract infection and sepsis, using standard in vitro susceptibility testing. Results: It could be shown that all species tested were exquisitely sensitive to everninomycin (MIC90 of 0.38 µg/ml for Staphylococcus aureus, 0.5 µg/ml for enterococci and 0.75 µg/ml for coagulase-negative staphylococci). Furthermore, no difference could be observed between methicillin-resistant and methicillin-sensitive S. aureus or between Enterococcus faecium and Enterococcus faecalis. Conclusions: These results suggest that everninomycin is a promising antibiotic for the treatment of nosocomial infections in intensive care unit patients and that the use of a related substance as an additive in animal food has not yet promoted resistance in clinical isolates.
In vitro Development of Resistance to Three Quinolones inStreptococcus pneumoniae
Authors: Rodríguez J.C. , Rodríguez J.C. , Llinares F. , Llinares F. , Royo G. , Royo G.
Published: April 2003

We studied the in vitro development of resistance to ciprofloxacin, trovafloxacin and moxifloxacin in 5 strains of Streptococcus pneumoniae resistant to penicillin. We detected the great ease of in vitro development of resistance in the case of ciprofloxacin and the much reduced capacity of moxifloxacin to generate resistance (only 1 strain). Trovafloxacin generated resistance, but more slowly than ciprofloxacin. We consider that study of the capacity to generate resistance should be one of the points to consider when deciding on their large-scale use in respiratory infections, but comparative studies between in vitro and in vivo models should be carried out so as to determine the clinical repercussion of these phenomena.
Bacteroides fragilis-Induced Intra-Abdominal Abscess in an Experimental Model Treated with Telithromycin (HMR 3647)
Authors: Thadepalli Haragopal , Thadepalli Haragopal , Chuah See Kean , Chuah See Kean , Qazi Shugufta , Qazi Shugufta , Thadepalli Fernando , Thadepalli Fernando , Gollapudi Sastry V. , Gollapudi Sastry V.
Published: April 2003

Background: Telithromycin (HMR 3647), a novel ketolide, is known to have activity against Bacteroides fragilis in vitro. Methods: We tested this ketolide in an animal model of intra-abdominal abscess produced by intraperitoneal injection of B. fragilis with sterile feces and BaSO4 mixture. Telithromycin was tested at two doses, 1.25 and 2.0 mg/dose twice daily, and compared with clindamycin, cefotetan or metronidazole, all given at 2.0 mg/dose twice daily for 10 days. Absence of bacteria at the infected site was considered a cure and a positive culture considered a failure. Results: The cure rate was 18% (5/28) on saline therapy, 74% (20/27) on telithromycin and 82% (23/28) on clindamycin, whereas it was 61% (17/28) on metronidazole and 59% (16/27) on cefotetan therapy. A high tissue antibiotic concentration (3–5 times the MIC) of telithromycin was found and this is presumably related to its superior efficacy. Delayed therapy initiated 7 days after infection instead of immediate therapy cured only 32% of the animals treated. The lower dose of telithromycin (1.25 mg/dose twice daily) was as effective as the higher dose (2 mg/dose twice daily). Conclusions: We found that telithromycin is as effective as clindamycin and more effective than metronidazole and cefotetan in this experimental model. These results suggest that telithromycin may be tested in future for the treatment of B. fragilis infections in humans.
Efficacy of a Benzalkonium Chloride-Impregnated Central Venous Catheter to Prevent Catheter-Associated Infection in Cancer Patients
Authors: Jaeger K. , Jaeger K. , Osthaus A. , Osthaus A. , Heine J. , Heine J. , Ruschulte H. , Ruschulte H. , Kuhlmann C. , Kuhlmann C. , Weissbrodt H. , Weissbrodt H. , Ganser A. , Ganser A. , Karthaus M. , Karthaus M.
Published: April 2003

Background: This study was performed to determine the efficacy of a benzalkonium chloride-impregnated central venous catheter (CVC) in preventing catheter-related infection in patients suffering from malignant diseases and undergoing chemotherapy. Methods: A randomized, prospective clinical trial was carried out to compare the incidence of catheter-related colonization and catheter-related bacteremia using an antiseptic-impregnated CVC (n = 25) with that using a standard triple-lumen CVC (n = 25). Results: All patients were treated with intensive chemotherapy for acute leukemia (n = 28), lymphoma (n = 17) or solid tumors (n = 5). Both study groups presented with similar data in regards to age, insertion site, duration of catheterization and neutropenia period during catheterization, demonstrating a comparable risk for catheter-related colonization. Suspicion of infection led to explantation in 14 versus 15 cases. Catheter-related colonization was proven in 4 cases (16%) and catheter-related bacteremia was observed only once (4%) in both groups. Statistical testing showed no significant differences between the study and control group. Conclusions: The rate of catheter-related colonization was lower than suspected in this high-risk patient group. The use of benzalkonium chloride-impregnated CVC failed to decrease the incidence of catheter-related colonization and bacteremia in patients with a high risk of infectious complications.
Experimental in vitro Efficacy Study on the Interaction of Epiroprim plus Isoniazid against Mycobacterium tuberculosis
Authors: Dosso Mireille , Ouattara Lassina , Cherif Abdou Magid , Bouzid Samir Amor , Haller Louis , Fernex Michel
Published: April 2003

Thirty Mycobacterium tuberculosis strains (8: INHR/INHR, 12: INHR/RIFS, 10: INHS/RIFS) were examined against MICs of epiroprim (EPM) and isoniazid (INH) separately or in association. EPM alone proved to be insufficiently active against the various mycobacterial isolates (MIC ≧256 µg/ml). The observed average sensitivity to the association of EPM plus INH was, in contrast, considerably increased, as reflected by reduced MICs and lower percentages of resistant strains. MICs ranged between 16 and 32 µg/ml EPM and 2 and 4 µg/ml INH for INHR strains. All INHS isolates were inhibited by a concentration of 0.125 µg/ml EPM and 0.06 µg/ml INH. The fractional inhibitory concentration indices indicated an additive activity on INHR/RIFR strains and a synergistic activity on INHR/RIFS and INHS/RIFS strains. The synergistic activity of this drug association needs to be confirmed in an animal model.
Inhibition of Telomerase Activity as a Measure of Tumor Cell Killing by Cisplatin in Squamous Cell Carcinoma Cell Line
Authors: Mese Hiroshi , Ueyama Yoshiya , Suzuki Atsushi , Nakayama Shuko , Sasaki Akira , Hamakawa Hiroyuki , Matsumura Tomohiro
Published: April 2003

Background: Telomerase is a ribonucleoprotein enzyme which is involved in the maintenance of chromosome ends. Telomerase activity is frequently associated with malignant phenotypes, and it can be considered a ubiquitous tumor marker. In this study we describe an approach for developing in vitro chemosensitivity assays based on the assessment of telomerase activity in squamous cell carcinoma to treatment with anticancer drugs. Methods: We used A431/CDDP1 and A431/CDDP2, two previously established cisplatin (CDDP)-resistant A431 sublines. These cell lines were not multidrug resistant but specifically resistant to the CDDP drug family. The telomeric repeat amplification protocol (TRAP assay) was used to measure telomerase activity in CDDP-resistant cell lines and to examine the effect of CDDP and other anticancer drugs on enzyme levels. We next analyzed the relations between telomerase activity and cytotoxic effects of CDDP in human squamous cell carcinoma (HSC2, HSC3, HSC4 and KB cell lines). Results: The telomerase activity of A431/CDDP1 and A431/CDDP2 was significantly higher than that of the parent A431 cell (A431/P) treated with CDDP and carboplatin at IC50. On the other hand, telomerase activity in these cell lines was not influenced by treatment with 5-fluorouracil, bleomycin, Adriamycin or taxol. The regression line derived from the quantitative analysis of the telomeric ladder versus IC50 of CDDP concentrations was analyzed. Telomerase activity was found to be positively correlated with the IC50 values for CDDP. Conclusions: The results of the present studies on in vitro squamous cell carcinoma cell lines indicate that telomerase activity inhibition can be used as a marker of tumor cell killing by CDDP. Therefore, the present investigation provides a rational basis for an in vitro chemosensitivity assay based on telomerase activity evaluation.
In vitro Effect of Amikacin, Imipenem, Cefodizime, IFNα-2a Alone and Combinations of Antibiotics with IFNα-2a on Polymorphonuclear Leukocyte Function in Chronic Hepatitis Patients
Authors: Adalati Rıza , Gürer Ümran Soyoğul , Çevikbaş Adile , Johansson Candan
Published: April 2003

The in vitro effect of amikacin (8 µg/ml), imipenem (30 µg/ml), cefodizime (10 µg/ml), interferon α-2a (IFNα-2a) (10 IU/ml) and antibiotic combinations with IFNα-2a on polymorphonuclear leukocyte (PMN) functions (phagocytosis and intracellular killing of Candida albicans blastospores) was investigated in chronic hepatitis B patients. Phagocytosis and candidacidal activity was not affected after pretreatment of PMNs with amikacin and imipenem (p > 0.05). Phagocytic activity was enhanced after pretreatment of PMNs with cefodizime and IFNα-2a compared with that of control PMNs (p < 0.05), but candidacidal activity was not affected by the same drugs (p > 0.05). Phagocytic and intracellular activity of PMNs were not affected by combinations of IFNα-2a and antibiotics (p > 0.05).
Pharmacokinetic Profile of the Anti-Sickling Hydroxyurea in Wild-Type and Transgenic Sickle Cell Mice
Authors: Iyamu W.E. , Lian L. , Asakura T.
Published: April 2003

The pharmacokinetic profile of hydroxyurea (HU) was investigated by measuring the rate of drug disappearance from the plasma in wild-type and transgenic (Tg) sickle cell mice. The absorption and elimination processes of HU exhibited first-order kinetics after intraperitoneal administration of HU at 10, 50, 100 or 200 mg/kg body weight (BW). The dosage had a marked effect on the pharmacokinetics of HU in the Tg sickle cell mice. Although the area under the plasma concentration curve (AUC) increased in direct proportion with the HU dose in the wild-type mice, the AUC increased to a much greater extent at higher doses in the Tg sickle cell mice. In the Tg sickle cell mice, there was a considerable increase in the mean residence time (MRT) and a significant reduction in the apparent clearance (CL/F) at HU dose ≧100 mg/kg BW, when compared to the lower doses. At an HU dose of 200 mg/kg BW, the CL/F in the Tg sickle cell mice was reduced by about 50% of the value obtained at a dose of 10 mg/kg BW. This phenomenon was not noticeable in the wild-type mice. The MRT value in the wild-type mice at all doses was relatively constant. The steady-state distribution volume of HU in both the wild-type and Tg sickle cell mice was relatively constant at all doses of the drug. The AUC, CL/F, MRT, and terminal half-life values at any given HU dose showed significant differences between the wild-type and Tg sickle cell mice. Following intraperitoneal administration of HU at a dose of 10, 50, 100, or 200 mg/kg BW, the mean percentage of HU excreted in the urine of the wild-type and Tg sickle cell mice over 120 min was 84 ± 6.4% and 50 ± 8.2%, respectively, indicating a significant difference in the amount of HU excreted in urine in the two kinds of mice. The results obtained in this study may be useful in establishing an optimal dose of HU in the treatment and management of patients with sickle cell disease and other hemoglobinopathies.
Evaluation of Polyene-Azole Antagonism in Liquid Cultures of Candida albicans Using an Automated Turbidometric Method
Authors: Samaranayake Y.H. , Samaranayake L.P. , Yeung K.W.S.
Published: April 2003

Background: A computerized machine, SPECTRAmax 340, was used to evaluate the recently reported phenomenon of antagonism of the polyene amphotericin B (AMB) in Candida albicans pre-exposed to the triazole fluconazole (FLZ). Methods: We investigated growth inhibition by varying concentrations of AMB in seven isolates of C. albicans pre-exposed to FLZ (50 µg/ml) for 18 h. All isolates were obtained on sequential visits from human immunodeficiency virus-infected patients not treated with FLZ. Results: Antagonism of AMB activity was observed in 5, 4, 2 and a single isolate for 0.5, 1, 2 and 3 µg/ml of the antifungal, respectively. In the majority of Candida isolates, antagonism was seen within a concentration range of 0.5–1.0 µg/ml AMB; 1 Candida strain (HK1-Sa) was resistant to 3 µg/ml AMB. Higher concentrations of AMB (>3 µg/ml) killed both the controls and FLZ-pre-exposed Candida cells. No significant differences were observed between the periods of antagonism observed for any of the sequential isolates or for any of the AMB concentrations or in the maxima of the growth curves obtained for all Candida isolates. Conclusion: We conclude that the SPECTRAmax system is a useful tool to evaluate in vitro pharmacodynamic interactions between antifungal regimens within a fluid culture system, and provides information that cannot be obtained using traditional plate assay systems.
Effects of Cefepime and Meropenem on the Gastrointestinal Colonization ofSurgical Patients by Candida albicans
Authors: Samonis G. , Thomakos N. , Liakakos T. , Macheras A. , Mandrekas D. , Kanavaki S. , Bafaloukos D. , Maraki S.
Published: April 2003

Background: The study evaluated the effects of cefepime and meropenem on the gastrointestinal (GI) colonization of surgical patients by Candida albicans. Patients and Methods: Twenty adult surgical patients who received intravenously either of these antibiotics as monotherapy for the treatment of an existing infection were studied prospectively. Ten patients received cefepime (2.0 g twice a day), and another ten meropenem (1.0 g every 8 h) for 7 days. Quantitative stool cultures for C. albicans were performed immediately before, at the end, and 1 week after the end of antibiotic treatment. Results: Both antibiotics increased the GI colonization of patients by Candida. Meropenem caused a higher increase (2.0 log10 CFU/g of stool) as compared to cefepime (1.7 log10 CFU/g of stool). However, these increases were statistically not significant. Conclusion: Cefepime and meropenem when given to sensitive patients do not increase significantly the risk of Candida infection originating in the GI tract.
Comparative Pharmacokinetics of Three Preparations of the New Antifungal SPK-843
Authors: Bruzzese T. , Galmozzi M.R. , Ferrari V.M. , Sala P. , Bonabello A.
Published: April 2003

The pharmacokinetics and tissue distribution of three preparations of SPK-843 (N-dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide diascorbate), a new polyene antibiotic with a heptaene structure, were compared in rats after a single 1.25 mg/kg intravenous administration. Blood and tissue samples were obtained at 0.25–96 h after injection. The serum pharmacokinetics of the three dosage forms of the antibiotic, A (5% glucose solution), B (10% lipid emulsion at pH 5.3) and C (10% lipid emulsion at pH 7.5), did not show large differences, the half-lives being 22.2, 26.5 and 23.2 h and the AUC0–∞ 35.5, 40 and 44.8 µg·h·ml–1 for preparations A, B and C, respectively. The tissue uptake of the two lipid-based preparations, particularly the spleen uptake, was greater than that of the glucose preparation, suggesting an active role of the lipid vehicle in tissue distribution.
Effects of Parenterally Administered Ciprofloxacin in a Murine Model of Pulmonary Pseudomonas aeruginosa Infection Mimicking Ventilator-Associated Pneumonia
Authors: Kaneko Yukihiro , Yanagihara Katsunori , Kuroki Misuzu , Ohi Hideo , Kakeya Hiroshi , Miyazaki Yoshitsugu , Higashiyama Yasuhito , Hirakata Yoichi , Tomono Kazunori , Kadota Jun-ichi , Kohno Shigeru
Published: April 2003

Background and Methods: We compared the bacteriological, pharmacological and histopathological effects of parenterally administered ciprofloxacin (CPFX) to those of imipenem/cilastatin (IMP/CS) and cefozopran (CZOP) in a murine model of mucoid Pseudomonas aeruginosa pneumonia mimicking ventilator-associated pneumonia. Results: The minimum inhibitory concentrations (MICs) of CPFX, IMP and CZOP were 1.0, 1.0 and 4.0 mg/l, respectively. Treatment with CPFX resulted in a significant decrease in the number of viable bacteria [control, IMP/CS, CZOP and CPFX (mean ± SEM): 5.02 ± 0.20, 4.96 ± 0.38, 5.44 ± 0.13 and 3.27 ± 0.02 log10 colony-forming units lung, respectively]. Histopathological examination revealed that inflammatory changes in the CPFX-treated group were less marked than in other groups. Of the drugs analyzed, the pharmacokinetic parameters of area under the time-concentration curve (AUC)/MIC, AUC exceeding MIC and the time that lung concentrations of drug remained above the MIC were highest for CPFX. Conclusion: Our results suggest that parenterally administered ciprofloxacin is effective in ventilator-associated P. aeruginosa pneumonia.
The Use of Outpatient Parenteral Antimicrobial Therapy in the Management of Osteomyelitis: Data from the Outpatient Parenteral Antimicrobial Therapy Outcomes Registries
Authors: Tice Alan
Published: April 2003

Because osteomyelitis requires lengthy parenteral antibiotic treatment in patients who are often otherwise healthy, it lends itself well to outpatient parenteral antibiotic therapy (OPAT). Four delivery models for OPAT are (1) self-administration at home, (2) administration by a visiting nurse in the home, (3) infusion center and (4) nursing home. Patient selection is critical to the success of any OPAT program. Clinical and microbiologic data were compiled for more than 500 osteomyelitis patients reported in a registry of OPAT cases in the United States. The most commonly isolated pathogen was Staphylococcus aureus. The antibiotics used most frequently were vancomycin and ceftriaxone. Of 255 patients assessed for bacteriologic outcome, 2 patients developed infection with a new organism and 2 failed to eliminate the causative organism by the end of OPAT therapy. Of 266 patients who were assessed for clinical outcome, 259 improved and 7 failed. Data collected by the OPAT Outcomes Registry confirms that osteomyelitis can be safely and effectively treated with intravenous antibiotics outside the hospital.