bluuebunny/crossref_metadata_2025 huggingface dataset:
A portable digital imaging system in dermatology: Diagnostic and educational applications
Authors: Lyon C C , Harrison P V
Published: October 2002

Digital photographs were taken by a trainee dermatologist of the presenting lesions of 100 unselected, consecutive new patients. For the 38 patients presenting with rashes there was clinical disagreement in only four cases (10%). For the 62 patients with tumours there was clinical disagreement in three cases (3.8%). In a further three cases both clinicians agreed on a differential diagnosis which was subsequently disproved by histological findings and clinical progress. The study demonstrated that an affordable, low-resolution, fixed-focus digital camera with close-up lenses could provide diagnostically useful images suitable for telediagnosis in dermatology.
Practising oncology via telemedicine
Authors: Doolittle Gary C , Allen Ace
Published: October 2002

Although there are increasing numbers of telemedicine programmes in the USA, few have offered teleoncology services, so that the role of telemedicine in the practice of clinical oncology has yet to be fully defined. Telemedicine has been used successfully for direct patient care in Kansas. It is also a method of providing supportive care for the cancer patient, including assessments of pain and nutrition. In addition, televised tumour conferences and nursing education courses can help smaller communities develop a level of expertise that allows patients to be treated locally. Telemedicine may well be used in future for access to national and international cancer experts, and for participation in new cancer treatment protocols through cooperative group trials. When practising oncology via telemedicine, there are unique problems, including issues regarding technology interactive video and radiograph review and practice patient oncologist preferences and doctor-patient communication . Very little has been published in the area of tele-oncology so far, and studies concerning its efficacy, cost-effectiveness and the best organizational structure are still in progress. However, telemedicine appears to be a useful technique in the practice of oncology.
Teleradiology: a review
Authors: Ruggiero C
Published: October 2002

Teleradiology, like telemedicine generally, has arisen because of the shift to digital communication and the demand for equal access to medical care. Unlike much of telemedicine, teleradiology can be shown to be cost effective in many situations, particularly if the alternatives are to transport the X-ray film to a radiologist or to use the services of a visiting radiologist circuit riding'. A teleradiology system consists of an image acquisition section and an image-display section, connected by a communications network. Considerable technical and clinical standardization work has been carried out e.g. by the American College of Radiology and commercial teleradiology systems are now available from a number of manufacturers. Up to 1994, more than 7000 teleradiology systems had been sold by the two largest manufacturers. Technology trends suggest that it will soon be common for clinicians to view digital radiographs from outside radiology departments and probably from outside a hospital environment as well.
Portable satellite telemedicine in practice
Authors: Navein J , Fisher A , Geiling J , Richards D , Roller J , Hagmann J
Published: October 2002

The US army's first portable telemedicine unit was built in 1993 and comprised a ‘ruggedized’ videoconferencing unit. The unit was initially used in the United Nations’ operations in Macedonia in February 1994 and subsequently in support of the Mobile Army Surgical Hospitals in Haiti, but its dimensions made it suitable only for locations where a move at short notice was unlikely. The second portable telemedicine unit comprised a PC linked to an Inmarsat B earth station through a modem. The unit allowed videoconferencing at 64 kbit/s. Three and a half years of clinical experience with both units has shown this to be quite adequate for the majority of clinical telemedicine. Portable telemedicine units have been a major benefit to medical commanders in the field.
Teleradiology: results of a questionnaire of German radiologists
Authors: Bolte R , Walz M , Lehmann K J , Hothorn T , Brill C , Hothorn L , Georgi M
Published: October 2002

A questionnaire was sent by mail to 4400 radiologists (i.e. to at least 1000 radiological institutions). The response rate was about 5%. The results showed that 47% of respondents felt well informed about teleradiology, 49% not enough and 3% not at all. Image and report transfer as well as interfaces to reference databases, educational applications, technical quality surveillance and product support (maintenance) were considered to be increasingly important areas. Smaller institutions (1–3 doctors) judged expert consultation as more important than bigger institutions. Standardization, system stability and data security were demanded as well as guidelines, for example concerning the linking of report and image, correct documentation and required image quality. Technically most demands can be fulfilled today but this technology is not yet commonly included in teleradiology systems.
A joint US–UK study of home telenursing
Authors: Wootton R , Loane M , Mair F , Allen A , Doolittle G , Begley M , Mcleman A , Moutray M , Harrisson S
Published: October 2002

Nursing notes for patients nursed at home in the USA and the UK were reviewed using an abstraction instrument developed and tested in the US. More than 1700 episodes of patient care at home were reviewed: 906 in the US and 839 in the UK. Preliminary data suggest that in the US approximately 45% of home nursing visits could be done via telemedicine, while the figure is lower in the UK, less than 15%. Pilot trials of ananalogue video-telephone in Kansas City and Belfast suggest that even relatively low-quality compressed video may be useful for home nursing. Clearly, there are differences between the two countries which merit further study, but there is evidence to suggest that telemedicine may have a role in the delivery of home health care.
A pilot trial of digital imaging in skin cancer
Authors: Whited J D , Mills B J , Hall R P , Drugge R J , Grichnik J M , Simel D L
Published: October 2002

We have used inexpensive off-the-shelf equipment for store-and-forward teledermatology and compared the precision and accuracy of digital image consultations with conventional, clinic-based consultations. Thirteen lesions were studied on 12 patients referred to a dermatology clinic for a suspected skin cancer. Patients were examined by two dermatologists. Subsequently, digital images were examined by two different dermatologists. There was almost complete agreement, both among and between the clinical and digital examiners, on differential diagnosis and biopsy recommendations. Agreement on the single most likely diagnosis was also good. Digital imaging shows promise in teledermatology.
The Mobile Hospital- an experimental telemedicine system for the early detection of disease
Authors: Shusuke Masaomi Takizawa , Takashima Sone Shodayu , Yuichiro Li Feng , Minoru Maruyama , Kazuhisa Hasegawa , Asakura Hanamura Kazuhiro
Published: October 2002

To detect early disease, especially lung disease, we created a new telemedicine system, called the Mobile Hospital. It consists of a satellite or ground communication system using a large vehicle in which is installed a whole-body spiral computerized tomography scanner and a multimedia telecommunications system. The Mobile Hospital goes to small villages and carries out mass screening for early lung disease, especially lung cancer. It travelled over 8000 km from May 1996 to March 1997. In this period 6358 persons aged 50-85 years and younger heavy smokers were screened in the Matsumoto area. As a result, 37.7 of the subjects were suspected of having various latent lung diseases. The cost of medical treatment for the lung cancers detected by the Mobile Hospital was 44 of that for a conventional medical care group, and the length of hospital treatment with surgical operation was 30 of that of the conventional group.
A pilot study of low-cost dynamic telepathology using the public telephone network
Authors: Vazir M. H. , Loane M. A. , Wootton R.
Published: October 2002

A pilot trial of a low-cost telepathology system was conducted. Avideo-codec operating to the CIF standard was used to transmit pictures over the public telephone network. Twenty-seven specimens from the routine pathology workload of a district hospital were examined. The average length of time spent examining each specimen was 14 min range 2-40 . The telepathology diagnoses were judged by conventional light microscopy of the specimens, performed by the same observer at a later date, and by a different observer. For the same observer, 23 diagnoses were correct 85 by telepathology, three were acceptable 11 and one was incorrect 4 . The results were slightly worse for a different observer: 21 diagnoses were correct 78 by telepathology, five diagnoses were acceptable 19 and one diagnosis was incorrect 4 . The technique was slower than conventional dynamic telepathology such as that based on communication by ISDN or leased circuits and picture quality was poor by comparison. However, these are not necessarily disadvantages in the context of the developing world, and since only a telephone connection is required, the technique could become an important method of improving the distribution of scarce resources, such as pathology expertise.
A prospective study of teleconferencing for orthopaedic consultations
Authors: Aarnio Pertti , Lamminen Heikki , Lepisto Jyri , Alho Antti
Published: October 2002

We carried out a prospective study of teleconsulting in orthopaedics. A commercial videoconferencing system was connected by three ISDN lines between the Satakunta Central Hospital in Pori and the Orton Orthopaedic Hospital in Helsinki, 240 km away. A document camera was used to transfer radiographic images and paper documents. Twenty-nine patients who needed an orthopaedic consultation were studied over three months. They were examined by a surgeon in Pori with the aid of teleconferencing and again later in a traditional, face to-face appointment in Helsinki. Patients and doctors completed questionnaires after the consultations. Technically, the videoconferencing system functioned reliably and the quality of the video was judged to be good. Twenty patients 69 would not have needed to travel for a face-to-face appointment, because the teleconsultation afforded a definite treatment decision. The orthopaedic surgeons considered all the treatment decisions arising from the teleconsultation good, except in one case which was considered satisfactory. The quality of the radiographic images transferred with the document camera was good or very good in 17 cases and satisfactory in three cases. None of the patients had experienced videoconferencing before; 87 of them thought that teleconsultation was a good or very good method and the rest felt that it was satisfactory. All patients wanted to participate in teleconsultations again and most would have recommended it to other patients.
Digital teledermatology for skin tumours: A preliminary assessment using a receiver operating characteristics (ROC) analysis
Authors: Lewis K , Gilmour E , Harrison P V , Patefield S , Dickinson Y , Manning D , Griffiths C
Published: October 2002

A low-cost store- and-forward teledermatology system using digital images for the remote diagnosis and management of skin tumours was evaluated Two hospitals participated in the trial. Patients were seen face to face at one hospital, and had their images and clinical history viewed remotely by a different dermatologist at a second hospital. A preliminary receiver operating characteristics (ROC) analysis revealed clinical agreement between the teledermatologist and face-to-face dermatologist in 93% of cases in terms of their assessment of the benign/malignant nature of the lesions. Sensitivity of the judgements was 88% and specificity was 80%. These preliminary findings indicate the potential for remote management of skin tumours using a low-cost system in the National Health Service.
A programme management model for the Nova Scotia telemedicine network
Authors: Campbell T , Martel R F
Published: October 2002

Sustainable telemedicine networks are not the norm but rather the exception. Unless a formal programme management model is in place, telemedicine can not be integrated successfully into the mainstream of modern healthcare. Critical factors in achieving sustainable telemedicine have been identified. The programme management model developed for the Nova Scotia Telemedicine Network incorporated the following tools: a telemedicine self-assessment indicator, service modelling, technical design and integration, application development and validation, scheduling, ongoing network management and evaluation.
Project RATEMA—one year's experience
Authors: Pieper B , Grossmann H P , Weiss M , Fliedner T M , Akleyev A V ,   RATEMA team, Wedel R , Schrezenmaier H , Duncker C , Bunjes D , Raghavachar A , Bergmann L , Gottlöber P , Peter R U , Schick R , Zhudinova N , Fomin V , Degteryova R G , Shalaginov S , Gudkova N , Zhidkova C , Klopotiuk V , Varfolomeyeva T
Published: October 2002

The RATEMA project is an international cooperation between the University of Ulm in Germany and the Urals Research Centre for Radiation Medicine in Chelyabinsk, Russia. For one year we conducted weekly conferences between the two sites, based on a satellite link with a 384 kbit/s connection. During the videoconferences the physicians on both sides—experts in radiation medicine—discussed the health status of Russian patients who had been chronically exposed to ionizing radiation in the South Urals region. The German partners presented patients with comparable haematological and oncological diseases. The project has shown the advantages and difficulties of working in an international and interdisciplinary environment. The experience gained has been very valuable for planning new projects with similar tasks. The results and the contents of the RATEMA database are the basis for education and research for physicians involved in the management of radiation victims.
Telemedicine and isolated communities: A UK perspective
Authors: Wootton Richard
Published: October 2002

There are still considerable inequalities in the provision of primary care in the UK in relation to need. Recruitment and retention of general practitioners (GPs) is a problem, although this is worse in inner-city than in rural areas. The main problem in rural areas of the UK is the accessibility of health services. GP consultation rates, hospital outpatient attendance rates and inpatient admissions all decline with distance both to the doctors’ surgeries and to hospitals. There is evidence that health services can be successfully and effectively delivered to isolated communities by telemedicine, but almost all of it relates to work done outside the UK. The experience has been generally good and should certainly be taken into account when planning future physician requirements and distribution.
Effects of metallic mercury on the perimenstrual symptoms and menstrual outcomes of exposed workers
Authors: Yang Jian‐Ming , Chen Qiong‐Yu , Jiang Xue‐Zhi
Published: October 2002

Background

Mercury is an important environmental and industrial pollutant and its effect on perimenstrual symptoms and menstrual outcomes is unclear.

Methods

A retrospective epidemiological investigation was conducted on 296 female workers exposed to mercury vapor and 394 female workers from food processing plants. Both groups included women of 18–44 years of age currently working since last at least 1 year when studied. Women who were currently pregnant, using oral contraceptives (Ocs), an intrauterine device (IUD), and steroid hormones were excluded.

Results

The air concentration of mercury in the workplace ranged from 0.001–0.200 mg/m3. The prevalence of abdominal pain in the exposed group was significantly higher than that in the control group (odds ratio (OR) = 1.47, 95% CI is 1.03–2.11). The prevalence of dysmenorrhea in the exposed group was significantly higher than that in the control group (OR = 1.66, 95% CI is 1.07–2.59).

Conclusions

An increased prevalence of abnormal menstruation was found in mercury‐exposed workers in China. Dysmenorrhea may be a useful biomarker for assessing female exposure to mercury occupationally. These observations suggest that further studies and preventive measures are warranted. Am. J. Ind. Med. 42:403–409, 2002. © 2002 Wiley‐Liss, Inc.
Comparison of clinical and patient‐based measures to assess medium‐term outcomes following shoulder surgery for disorders of the rotator cuff
Authors: Dawson Jill , Hill Graham , Fitzpatrick Ray , Carr Andrew
Published: October 2002

Objective

To compare different assessments following shoulder surgery for impingement syndrome with or without rotator cuff tear or repair.

Methods

A prospective study of 93 patients was conducted. Standard assessments were performed before, at 6 months, and at 4 years following shoulder surgery using the patient‐based Oxford Shoulder Score (OSS), the Medical Outcomes Study Short Form‐36 (SF‐36) questionnaire, and a surgeon‐assessed Constant Shoulder Score. Patients were categorized according to the surgery received in relation to the presence of cuff tears: full repair, partial repair, cuff tear/no repair, no tear/no repair.

Results

Most patients (57%) received subacromial decompression for impingement with no cuff tear. This group had the fewest pre‐ and postoperative symptoms. The category of patients who received only partial repair of a cuff tear had worse scores on all outcome assessments compared with other groups. Patient‐based measures were more stable over time than the Constant.

Conclusion

The shoulder‐specific measures had greater sensitivity than the SF‐36 in registering significant differences in outcomes between comparison groups at 6 months and 4 years.
Kinesthesia at the knee: The effect of osteoarthritis and bandage application
Authors: Hewitt Bronwen A. , Refshauge Kathryn M. , Kilbreath Sharon L.
Published: October 2002

Objective

To investigate whether osteoarthritis (OA) of the knee or bandaging of the knee affects movement detection.

Methods

Movement detection levels were determined in 10 women aged > 65 years with moderate to severe knee OA and 10 healthy women matched for age, body mass index, and activity levels. Movements were imposed at 0.5°/second, 1.0°/second, and 2.5°/second. Additionally, detection levels were compared with and without the knee bandaged at a single velocity, (0.5°/second).

Results

Controls perceived significantly smaller movements than OA subjects at all test velocities (P < 0.01). However, the bandage did not affect movement detection (P > 0.05).

Conclusions

Detection of movement at the knee was impaired in subjects with severe knee OA, and a bandage did not improve detection. Thus, considering previous findings that position sense is impaired, a generalized proprioceptive deficit appears to be associated with OA. This deficit could result from loss of receptors, altered muscle function, or the consequent joint instability.
Visual subdivisions of the dorsal ventricular ridge of the iguana (Iguana iguana) as determined by electrophysiologic mapping
Authors: Manger Paul R. , Slutsky Daniel A. , Molnár Zoltán
Published: October 2002

The dorsal ventricular ridge (DVR) of reptiles is one of two regions of the reptilian telencephalon that receives input from the dorsal thalamus. Although studies demonstrate that two visual thalamic nuclei, the dorsal lateral geniculate and rotundus, send afferents to the dorsal cortex and DVR, respectively, relatively little is known about physiologic representations. The present study determined the organization of the visual recipient region of the iguana DVR. Microelectrode mapping techniques were used to determine the extent, number of subdivisions, and retinotopy within the visually responsive region of the anterior DVR (ADVR). Visually responsive neurons were restricted to the anterior two thirds of the ADVR. Within this region, two topographically organized subdivisions were determined. Each subdivision contained a full representation of the visual field and could be distinguished from the other by differences in receptive field properties and reversals in receptive field progressions across their mutual border. A third subdivision of the ADVR, in which neurons are responsive to visual stimulation is also described; however, a distinct visuotopic representation could not be determined for this region. This third region forms a shell surrounding the lateral, dorsal, and medial aspects of the topographically organized subdivisions. These results demonstrate that there are multiple physiologic subdivisions in the thalamic recipient zone of the ADVR of the iguana. Comparisons to the ADVR of other reptiles are made, homologies to ectostriatial regions of the bird are proposed, and the findings are discussed in relation to telencephalic organization of other vertebrates. J. Comp. Neurol. 453:226–246, 2002. © 2002 Wiley‐Liss, Inc.
Developmental anomalies and neoplasia in animals and cells deficient in the large zinc finger protein KRC
Authors: Allen Carl E. , Muthusamy Natarajan , Weisbrode Steven E. , Hong Joung Woo , Wu Lai‐Chu
Published: October 2002

The large zinc finger protein KRC binds to the signal sequences of V(D)J recombination and the κB motif. Disruption of KRC expression in cell lines resulted in increased cell proliferation, anchorage independence of growth, and uncoupling of nuclear division and cell division. In this report, the function of KRC was studied in a RAG2‐deficient blastocyst complementation animal model. KRC‐deficient embryonic stem cells were generated by homologous recombination and were introduced into RAG2−/− blastocysts to generate KRC−/−;RAG2−/− chimeric mice. The lymphoid compartments of chimeras examined at 5 weeks of age were developed, suggesting that KRC is not essential for V(D)J recombination development. However, by 6 months of age, there was a marked deficit in CD4+CD8+ thymocytes in the chimeras, suggesting that KRC may be involved in T‐lymphocyte survival. Additionally, one chimera developed anomalies, including postaxial polydactyly, hydronephrosis, and an extragonadal malignant teratoma. DNA analysis showed that the teratoma was derived from KRC−/− embryonic stem cells. The teratoma had compound tissue organization and was infiltrated with B lymphocytes. Subsequently, several immortalized KRC‐deficient cell lines were established from the teratoma. In this study, growth anomalies and neoplasia were observed in animals and cells deficient in KRC, and other studies have shown allelic loss occurring at the chromosomal region of the human KRC counterpart in various tumors. We propose that KRC may be a previously unidentified tumor‐suppresser gene. © 2002 Wiley‐Liss, Inc.
Identification of the breakpoints at 1p36.2 and 3p21.3 in an AML(M3) patient who had t(1;3)(p36.2;p21.3) at the third relapse
Authors: Tri Nguyen Khanh , Xinh Phan Thi , Nagao Hiromasa , Izumi Tohru , Ozawa Keiya , Toyoda Atsushi , Hattori Masahira , Sakaki Yoshiyuki , Tokunaga Katsushi , Sato Yuko
Published: October 2002

Recently, we reported that a recurrent translocation, t(1;3)(p36;p21) is closely associated with prior chemotherapy including alkylating agents, assessing eight patients with various hematologic malignancies (Genes, Chromosomes and Cancer 34:186–192), 2002). Furthermore, we delineated the 1p36 breakpoint in two patients lying between RP11‐BAC47P3 and RP5‐PAC963K15 at 1p36.3 with a small deletion near the breakpoint. In one of them, we also found deletion at 3p21.3 with cosNRL9 probe, which is included in a 370‐kb lung cancer homologous deletion region. However, due to scantiness of the patient materials at that time, we could not determine the precise breakpoint at 1p36 or 3p21 in any of the patients. In this report, we identified the 1p36 and 3p21 breakpoints of an AML (M3) patient who is included in the previous patient series. The patient showed t(1;3)(p36;p21) together with t(15;17) at the third relapse. With FISH using BAC/PAC probes, we determined the 1p36 breakpoint within RP11‐295B1 at 1p36.2 and the 3p21 breakpoint between RP11‐3B7 and RP11‐901L6 at 3p21.3. There was no deletion around the two breakpoints in this patient. To the best of our knowledge, this is the first report that has identified the precise breakpoint of t(1;3)(p36;p21) translocation. It is obvious that the 1p36.2 and 3p21.3 breakpoints of this patient are different from those of the previous patients, suggesting that the genes and the molecular event is different from those of the previous patients. The patients with t(1;3)(p36;p21) should be subclassified according to the precise breakpoints or the genes involved. © 2002 Wiley‐Liss, Inc.
Transient leukopenia and anaphylatoxin production during granulocyte apheresis as treatment for ulcerative colitis
Authors: Yonemura Katsuhiko , Ohashi Naro , Kajimura Masayoshi , Hishida Akira
Published: October 2002

It is well known that transient leukopenia due to activation of the alternative pathway of the complement system accompanies hemodialysis when cellulose acetate dialyzers are used. However, it has not been evaluated whether leukopenia also occurs during granulocyte apheresis (GCAP) as treatment for ulcerative colitis, in which an extracorporeal column is filled with cellulose acetate beads in order to remove circulating leukocytes. The aim of the present study was to evaluate whether transient leukopenia and activation of the alternative pathway of the complement system were observed during GCAP. In 8 patients undergoing GCAP weekly for 10 weeks, circulating leukocyte counts and plasma concentrations of C3a, a product of the activated alternative pathway of the complement system, were determined. GCAP elicited a rapid decline in the number of circulating leukocytes to 61.8 ± 13.8% of the baseline value after 15 minutes of GCAP (P < 0.02). Thereafter, the number of circulating leukocytes returned to approximately baseline after 60 minutes. The baseline plasma C3a concentration was 123 ± 61 ng/mL, and a significant increase to 425 ± 123 ng/mL was observed after 15 minutes of GCAP (P < 0.02). The plasma C3a concentration reached 417 ± 96 ng/mL after 60 minutes (P < 0.02). It thus follows that GCAP activates the alternative pathway of the complement system, resulting in anaphylatoxin production. J. Clin. Apheresis 17:107–110, 2002. © 2002 Wiley‐Liss, Inc.
Depression in Alzheimer’s disease: is there a temporal relationship between the onset of depression and the onset of dementia?
Authors: Heun Reinhard , Kockler Martin , Ptok Ursula
Published: October 2002

Alzheimer’s disease (AD) patients often present with concurrent major depression (MD). To investigate the reasons for this comorbidity, e.g. MD being a risk factor for AD, or both diagnoses having a common neurobiology, the temporal relationship between the first onset of AD and of MD during lifetime was investigated—57 out of 146 AD patients had a lifetime diagnosis of MD. The correlation between the ages at onset of MD and dementia was calculated. The incidence of MD in AD patients in several 5-year-intervals before and after the onset of AD was compared with the average incidence of MD in the present AD sample and with the expected incidence of MD in the general population. No significant correlation between the onset of AD and of MD could be found after controlling for age, gender and the Mini-Mental-State. However, the incidence of MD 5 years before and after the onset of AD significantly exceeded the expected incidences—MD is only partially related to AD. However, the increased incidence of MD within 5 years before and after the onset of dementia may indicate that a common neurobiological process causes cognitive decline and depression in a subsample of AD patients.
Antivaccinia Activities of Acyclic Nucleoside Phosphonate Derivatives in Epithelial Cells and Organotypic Cultures
Authors: Snoeck R. , Holý A. , Dewolf-Peeters C. , Van Den Oord J. , De Clercq E. , Andrei G.
Published: October 2002

Organotypic “raft” cultures of epithelial cells allow the reconstitution of a skin equivalent that is easily infectible with different viruses with cutaneous tropism. Among these, poxvirus and particularly vaccinia virus (VV) are good candidates for use in antiviral tests, giving histological pictures comparable to those observed in humans infected with smallpox. Therefore, we decided to evaluate a series of phosphonate derivatives for their ability to inhibit VV growth in epithelial cell monolayers, and the most powerful derivatives were tested in the organotypic cultures. The most active compound was 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine [(S)-HPMPA], followed by 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine, cyclic (S)-HPMPA, 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine [(S)-HPMPC; cidofovir, Vistide], and cyclic (S)-HPMPC. Cidofovir, which is on the market for the treatment of human cytomegalovirus retinitis in immunocompromised patients, is potentially a good candidate for the treatment of a poxvirus outbreak, in the absence of any vaccination.
Dual Targeting of DNA Gyrase and Topoisomerase IV: Target Interactions of Garenoxacin (BMS-284756, T-3811ME), a New Desfluoroquinolone
Authors: Ince Dilek , Zhang Xiamei , Silver L. Christine , Hooper David C.
Published: October 2002

We determined the target enzyme interactions of garenoxacin (BMS-284756, T-3811ME), a novel desfluoroquinolone, in
Staphylococcus aureus
by genetic and biochemical studies. We found garenoxacin to be four- to eightfold more active than ciprofloxacin against wild-type
S. aureus.
A single topoisomerase IV or gyrase mutation caused only a 2- to 4-fold increase in the MIC of garenoxacin, whereas a combination of mutations in both loci caused a substantial increase (128-fold). Overexpression of the NorA efflux pump had minimal effect on resistance to garenoxacin. With garenoxacin at twice the MIC, selection of resistant mutants (<7.4 × 10
−12
to 4.0 × 10
−11
) was 5 to 6 log units less than that with ciprofloxacin. Mutations inside or outside the quinolone resistance-determining regions (QRDR) of either topoisomerase IV, or gyrase, or both were selected in single-step mutants, suggesting dual targeting of topoisomerase IV and gyrase. Three of the novel mutations were shown by genetic experiments to be responsible for resistance. Studies with purified topoisomerase IV and gyrase from
S. aureus
also showed that garenoxacin had similar activity against topoisomerase IV and gyrase (50% inhibitory concentration, 1.25 to 2.5 and 1.25 μg/ml, respectively), and although its activity against topoisomerase IV was 2-fold greater than that of ciprofloxacin, its activity against gyrase was 10-fold greater. This study provides the first genetic and biochemical data supporting the dual targeting of topoisomerase IV and gyrase in
S. aureus
by a quinolone as well as providing genetic proof for the expansion of the QRDRs to include the 5′ terminus of
grlB
and the 3′ terminus of
gyrA.
Identification of a Chromosome-Borne Expanded-Spectrum Class A β-Lactamase from
Erwinia persicina
Authors: Vimont Sophie , Poirel Laurent , Naas Thierry , Nordmann Patrice
Published: October 2002

From whole-cell DNA of an enterobacterial
Erwinia persicina
reference strain that displayed a penicillinase-related antibiotic-resistant phenotype, a β-lactamase gene was cloned and expressed in
Escherichia coli.
It encoded a clavulanic-acid-inhibited Ambler class A β-lactamase, ERP-1, with a pI value of 8.1 and a relative molecular mass of ca. 28 kDa. ERP-1 shared 45 to 50% amino acid identity with the most closely related enzymes, the chromosomally encoded enzymes from
Citrobacter koseri
,
Kluyvera ascorbata
,
Kluyvera cryocrescens
,
Klebsiella oxytoca
,
Proteus vulgaris
,
Proteus penneri
,
Rahnella aquatilis
,
Serratia fonticola
,
Yersinia enterocolitica
, and the plasmid-mediated enzymes CTX-M-8 and CTX-M-9. The substrate profile of the noninducible ERP-1 was similar to that of these β-lactamases. ERP-1 is the first extended-spectrum β-lactamase from an enterobacterial species that is plant associated and plant pathogenic.
Complete Nucleotide Sequence of
Klebsiella pneumoniae
Multiresistance Plasmid pJHCMW1
Authors: Sarno Renee , McGillivary Glen , Sherratt David J. , Actis Luis A. , Tolmasky Marcelo E.
Published: October 2002

The multiresistance plasmid pJHCMW1, harbored by a clinical
Klebsiella pneumoniae
strain isolated from a neonate with meningitis, was sequenced. A circular sequence of 11,354 bp was generated, of which 7,993 bp make up Tn
1331
, a transposon including the antibiotic resistance genes
aac
(
6
′)
-Ib
,
aadA1
,
bla
OXA-9
, and
bla
TEM-1
. The gene
aac
(
6
′)
-Ib
is included in a gene cassette, and both
aadA1
and
bla
OXA-9
are included in a single-gene cassette that may have arisen as a consequence of a recombination event involving two integrons. The pJHCMW1 plasmid replicates through a ColE1-like RNA-regulated mechanism, includes a functional
oriT
, and two loci with similarity to XerCD site-specific recombination target sites involved in plasmid stabilization by the resolution of multimers. One of these two loci,
mwr
, is active and has been the subject of previous studies, and the other,
dxs
, is not functional but binds the recombinase XerD with low affinity. Two additional open reading frames were identified, one with low similarity to two hypothetical membrane proteins from
Mycobacterium tuberculosis
and
Mycobacterium leprae
and the other with low similarity to
psiB
, a gene encoding a function that facilitates the establishment of the transferring plasmid in the recipient bacterial cell during the process of conjugation.
In Vivo Pharmacodynamics of a New Oxazolidinone (Linezolid)
Authors: Andes D. , van Ogtrop M. L. , Peng J. , Craig W. A.
Published: October 2002

Linezolid is a new oxazolidinone with activity against gram-positive cocci. We determined the in vivo activity of linezolid against four strains of
Staphylococcus aureus
(two methicillin-susceptible
S. aureus
[MSSA] strains and two methicillin-resistant
S. aureus
strains) and one penicillin-susceptible
Streptococcus pneumoniae
(PSSP) strain, two penicillin-intermediate
S. pneumoniae
strains, and five penicillin-resistant
S. pneumoniae
strains. The mice had 10
6.3
to 10
7.7
CFU/thigh before therapy and were then treated for 24 h with 5 to 1,280 mg of linezolid/kg divided into 1, 2, 4, 8, or 16 doses. The killing activities after 4 h of therapy ranged from 2.4 to 5.0 log
10
CFU/thigh against
S. pneumoniae
and 1.35 to 2.2 log
10
CFU/thigh against
S. aureus
. Increasing doses produced minimal concentration-dependent killing; doses of 20 and 80 mg/kg produced no in vivo postantibiotic effects (PAEs) with PSSP and modest PAEs (3.4 and 3.2 h) with MSSA. Pharmacokinetic studies at doses of 20 and 80 mg/kg by high-pressure liquid chromatography analysis exhibited peak dose values of 0.68 and 0.71 and elimination half-lives of 1.02 and 1.00 h. Linezolid MICs ranged from 0.5 to 1.0 μg/ml for
S. pneumoniae
and from 1.0 to 4.0 μg/ml for
S. aureus
. A sigmoid dose-response model was used to estimate the dose required to achieve a net bacteriostatic effect over 24 h. Static doses against
S. pneumoniae
ranged from 22.2 to 97.1 mg/kg/24 h and from 133 to 167 mg/kg/24 h for
S. aureus
. The 24-h area under the concentration-time curve (AUC)/MIC ratio was the major parameter determining the efficacy of linezolid against PSSP (
R
2
= 82% for AUC/MIC versus 57% for T>MIC and 59% for the peak level in serum/MIC [peak/MIC]). It was difficult to determine the most relevant pharmacokinetic/pharmacodynamic parameter with
S. aureus
, although the outcomes correlated slightly better with the 24-h AUC/MIC ratio (
R
2
= 75%) than with the other parameters (T>MIC
R
2
= 75% and peak/MIC
R
2
= 65%). The 24-h AUC/MIC ratio required for a bacteriostatic effect with linezolid varied from 22 to 97 (mean = 48) for pneumococci and from 39 to 167 (mean = 83) for staphylococci. Based upon a pharmacokinetic goal of a 24-h AUC/MIC of 50 to 100, a dosage regimen of 600 mg given either intravenously or orally twice daily would achieve success against organisms with MICs as high as 2 to 4 μg/ml.
Antifungal Activity of Amphotericin B, Fluconazole, and Voriconazole in an In Vitro Model of
Candida
Catheter-Related Bloodstream Infection
Authors: Lewis Russell E. , Kontoyiannis Dimitrios P. , Darouiche Rabih O. , Raad Issam I. , Prince Randall A.
Published: October 2002

The activity of five simulated antifungal regimens for eradication of catheter-related bloodstream
Candida
infection was evaluated with an in vitro pharmacodynamic model. Single-lumen central venous catheters were colonized with
Candida
species by sequentially incubating central venous catheters in plasma and then in growth medium (RPMI plus morpholinepropanesulfonic acid) containing a standardized suspension (10
5
CFU/ml) of
Candida albicans
,
Candida glabrata
, or slime-producing
Candida parapsilosis
. Colonized central venous catheters were then placed in a one-compartment pharmacodynamic model where five antifungal regimens (plus control) were simulated: amphotericin B, 1.0 mg/kg every 24 h; amphotericin B, 0.5 mg/kg every 24 h; fluconazole, 400 mg every 24 h; fluconazole, 800 mg every 24 h; and voriconazole, 4 mg/kg every 12 h. During exposure to the simulated clinical regimens, samples were serially removed from the model over 48 h for quantitation of viable organisms. All antifungal regimens suppressed fungal counts by both peripheral and catheter sampling versus control (
P
= 0.001). Overall, antifungal activity ranked amphotericin B (1 mg/kg) > amphotericin B (0.5 mg/kg) ≥ voriconazole > fluconazole (800 mg) ≥ fluconazole (400 mg). No regimen, however, completely eradicated (by culture and electron microscopy) central venous catheter colonization. Regrowth was noted in the model during therapy against
C. glabrata
and
C. parapsilosis
but was not associated with an increase in the MICs for the isolates. Lack of in vitro antifungal activity against biofilm-encased organisms appeared to be the primary reason for mycological failure of antifungal regimens in the model.
Pharmacokinetics of Ertapenem in Healthy Young Volunteers
Authors: Majumdar A. K. , Musson D. G. , Birk K. L. , Kitchen C. J. , Holland S. , McCrea J. , Mistry G. , Hesney M. , Xi L. , Li S. X. , Haesen R. , Blum R. A. , Lins R. L. , Greenberg H. , Waldman S. , Deutsch P. , Rogers J. D.
Published: October 2002

Ertapenem (INVANZ) is a new once-a-day parenteral β-lactam antimicrobial shown to be effective as a single agent for treatment of various community-acquired and mixed infections. The single- and multiple-dose pharmacokinetics of ertapenem at doses up to 3 g were examined in healthy young men and women volunteers. Plasma and urine samples collected were analyzed using reversed-phase high-performance liquid chromatography with UV detection. Ertapenem is highly bound to plasma protein. The protein binding changes from ∼95% bound at concentrations of <50 μg/ml to ∼92% bound at concentrations of 150 μg/ml (concentration at the end of a 30-min infusion following the 1-g dose). The nonlinear protein binding of ertapenem resulted in a slightly less than dose proportional increase in the area under the curve from 0 h to infinity (AUC
0-∞
) of total ertapenem. The single-dose AUC
0-∞
of unbound ertapenem was nearly dose proportional over the dose range of 0.5 to 2 g. The mean concentration of ertapenem in plasma ranged from ∼145 to 175 μg/ml at the end of a 30-min infusion, from ∼30 to 34 μg/ml at 6 h, and from ∼9 to 11 μg/ml at 12 h. The mean plasma
t
1/2
ranged from 3.8 to 4.4 h. About 45% of the plasma clearance (CL
P
) was via renal clearance. The remainder of the CL
P
was primarily via the formation of the β-lactam ring-opened metabolite that was excreted in urine. There were no clinically significant differences between the pharmacokinetics of ertapenem in men and women. Ertapenem does not accumulate after multiple once-daily dosing.
Emergence in Vietnam of
Streptococcus pneumoniae
Resistant to Multiple Antimicrobial Agents as a Result of Dissemination of the Multiresistant Spain
23F
-1 Clone
Authors: Parry Christopher M. , Duong Nguyen Minh , Zhou Jiaji , Mai Nguyen Thi Hoang , Diep To Song , Thinh Le Quoc , Wain John , Van Vinh Chau Nguyen , Griffiths David , Day Nicholas P. J. , White Nicholas J. , Hien Tran Tinh , Spratt Brian G. , Farrar Jeremy J.
Published: October 2002

Surveillance for
Streptococcus pneumoniae
resistant to penicillin and other antimicrobial agents is necessary to define the optimal empirical antibiotic therapy for meningitis in resource-poor countries such as Vietnam. The clinical and microbiological features of 100 patients admitted to the Centre for Tropical Diseases in Ho Chi Minh City, Vietnam, between 1993 and 2002 with invasive pneumococcal disease were studied. A penicillin-nonsusceptible pneumococcus (MIC, ≥0.1 μg/ml) was isolated from the blood or cerebrospinal fluid of 8% of patients (2 of 24) between 1993 and 1995 but 56% (20 of 36) during 1999 to 2002 (
P
< 0.0001). Pneumococcal isolates resistant to penicillin (MIC, ≥2.0 μg/ml) increased from 0% (0 of 24) to 28% (10 of 36) (
P
= 0.002). Only one isolate was ceftriaxone resistant (MIC, 2.0 μg/ml). Penicillin-nonsusceptible pneumococci were isolated from 78% of children younger than 15 years (28 of 36) compared with 25% of adults (16 of 64) (
P
= 0.0001). Isolation of a penicillin-nonsusceptible pneumococcus in adults with meningitis was independently associated with referral from another hospital (
P
= 0.005) and previous antibiotic therapy (
P
= 0.025). Multilocus sequence typing showed that 86% of the invasive penicillin-resistant pneumococcus isolates tested (12 of 14) were of the Spain
23F
-1 clone. The serotypes of >95% of the penicillin-nonsusceptible pneumococci were included in the currently available pneumococcal vaccines. Our findings point to the recent introduction and spread of the Spain
23F
-1 clone of penicillin-resistant pneumococci in Vietnam. Simple clinical predictors can be used to guide empirical antibiotic therapy of meningitis. Pneumococcal vaccination may help to control this problem.
In Vitro and In Vivo Activities of Newer Fluoroquinolones against
Vibrio vulnificus
Authors: Tang Hung-Jen , Chang Ming-Chung , Ko Wen-Chien , Huang Kun-Yen , Lee Chih-Lung , Chuang Yin-Ching
Published: October 2002

The MICs of six fluoroquinolones as well as minocycline and cefotaxime for 46 clinical isolates of
Vibrio vulnificus
were determined by the agar dilution method. All the drugs tested had good activities against all isolates, with the MICs at which 90% of the isolates tested were inhibited (MIC
90
s) by five of the fluoroquinolones ranging between 0.03 and 0.06 μg/ml. The MIC
90
of lomefloxacin, on the other hand, was 0.12 μg/ml. Time-kill studies were conducted with these agents and a clinical strain of
V. vulnificus
, VV5823. When approximately 5 × 10
5
CFU of
V. vulnificus
/ml was incubated with any one of the above-mentioned six fluoroquinolones at concentrations of two times the MIC, there was an inhibitory effect on
V. vulnificus
that persisted for more than 48 h with no noted regrowth. The efficacies of the fluoroquinolones were further evaluated in vivo in the mouse model of experimental
V. vulnificus
infection and compared to the efficacy of a combination therapy using cefotaxime plus minocycline. With an inoculum of 1.5 × 10
7
CFU, 28 (87.5%) of 32 mice in the cefotaxime-minocycline-treated group survived and 29 (91%) of the 32 mice in the moxifloxacin-treated group survived while none of the 32 mice in the control group did. With an inoculum of 3.5 × 10
7
CFU, the difference in survival rates among groups of 15 mice treated with levofloxacin (13 of 15), moxifloxacin (10 of 15), gatifloxacin (10 of 15), sparfloxacin (11 of 15), ciprofloxacin (12 of 15), or lomefloxacin (10 of 15) was not statistically significant while none of the 15 mice treated with saline survived. We concluded that the newer fluoroquinolones as single agents are as effective as the cefotaxime-minocycline combination in inhibiting
V. vulnificus
both in vitro and in vivo.
In Vitro Antibacterial Activities of Phloxine B and Other Halogenated Fluoresceins against Methicillin-Resistant
Staphylococcus aureus
Authors: Rasooly Avraham , Weisz Adrian
Published: October 2002

Fluorescein dyes in which the benzoic acid moiety has been tetrachlorinated (50 to 100 μg/ml) inhibit in vitro
Staphylococcus aureus
growth (MIC, 25 μg/ml). Specifically, under standard room illumination, phloxine B at a concentration of 100 μg/ml killed 99% of the cultures (mid-log phase). It also reduced
S. aureus
CFU by 10
4
. Structure-activity analysis revealed that the activity against
S. aureus
increases with the increase in the number of the substituting halogens in the hydroxyxanthene moiety.
Decolorization and destruction of metallophthalocyanines in aqueous medium by ultrasound: a feasibility study
Authors: Tu Shih Pin , Kim Daeik , Yen Teh Fu
Published: October 2002

Most currently available treatment methods for the phthalocyanine type of pigments have shortcomings and problems. An alternative approach using chemical-assisted ultrasound was conducted and the feasibility for the decolorization and destruction of the metallophthalocyanines has been demonstrated. Both copper and nickel phathlocyanine, with water and organic solvents at ambient temperature and atmospheric pressure in the presence of catalytic amount of oxidant under 20 kHz of frequency at a power level of 3759 W/cm2, can reach a destructive level of 9295% within 50 min. Preliminary kinetic studies found that the process belongs to the Langmuir-Hinshelwood type. The reaction mechanism is similar to that of metalloporphyrins, and the intermediate is an unstable ion radical that can release metal. Key words: metallophthalocyanines, ultrasound, decolorization, destruction, demetallation, dyebath wastes.
Implications of movement patterns for gene flow in black rat snakes (Elaphe obsoleta)
Authors: Blouin-Demers Gabriel , Weatherhead Patrick J
Published: October 2002

Gene flow is fundamental to evolutionary processes but knowledge about movements of individuals and their offspring necessary for gene flow is scant. We investigated potential ecological components of genetic connectivity within a population of black rat snakes (Elaphe obsoleta) by radio-tracking 82 individuals. Because adult black rat snakes are highly faithful to their hibernaculum, gene flow between hibernaculum populations has to occur through mating between members of different hibernacula or through juvenile dispersal. The present study was the first to assess the spatial dispersion of a complete network of hibernacula. The mean distance between the nearest-neighbour hibernacula was 811 m, which was less than the mean distances that reproductive males and females were found from their hibernacula during the mating season. Estimates of maximum distances individuals were from their hibernacula during the mating season indicated that, on average, a female was likely to mate with males that came from two hibernacula away from the female's own hibernaculum. Both males and females appeared to contribute actively to gene flow by moving more and increasing their distance from their hibernacula during the mating season. In addition, on average, females nested closer to a hibernaculum other than the one they attended, thereby potentially increasing the likelihood that their offspring would join hibernacula other than their mothers'. Thus, spatial and movement patterns of male and female black rat snakes are consistent with genetic evidence of extensive out-breeding among local hibernaculum populations.