bluuebunny/crossref_metadata_2025 huggingface dataset:
Tele-education: The virtual medical laboratory
Authors: Alusi G H , Tan A C , Campos J C , Linney A , Wright A
Published: October 2002

The virtual medical laboratory (VML) was conceived to provide an Internet-accessible resource, offering access for clinicians and scientists to an invaluable data archive at the Institute of Laryngology and Otology, London. The Institute is home to the largest collection of temporal bone, laryngeal, skull and sinus sections in Europe. The skull and sinus collections include an extensive section consisting of animal material. These were contributions from zoos around the world. Over the last 50 years, samples have been carefully sectioned and stained by specialized technicians to produce histology slices of most regions of the head and neck. The aim of the project is to create a virtual medical laboratory, which will provide access to archived histological material as well as computerized tomography and magnetic resonance data. Central to this aim is the reconstruction of the internal anatomy of the temporal bone from two-dimensional histology slices, to create three-dimensional views that can be used for anatomical simulation and surgical training in otolaryngology. State-of-the-art three-dimensional reconstruction and rendering technology allows us to develop such a model. Computer-generated simulation could be made available to all hospitals in which otolaryngology is practised, via digital communication networks. We aim to develop core technology in our own specialty that is applicable to other fields of higher education, which have not been exposed to such modern teaching modalities. This has the potential to become an invaluable teaching resource for anatomists, surgeons and other scientists.
Is there a role for telemedicine in an urban environment?
Authors: Harrison R M , Clayton W , Wallace P
Published: October 2002

Semi-structured interviews were carried out to determine the expectations of potential participants in a feasibility study of teleconsulting. General practitioners produced high positive scores in all areas. Hospital consultants produced high scores but were more critical of technical performance and administrative arrangements. Patient satisfaction with teleconsulting was generally good. The results suggested that teleconsulting was both feasible and acceptable to the users.
A portable unit for remote monitoring of pacemaker patients
Authors: Barbaro V , Bartolini P , Bernarducci R
Published: October 2002

The number of people with pacemakers has been steadily increasing over the past 20 years. At present there are about 2,500,000 in the world. All these patients must have a checkup twice a year in hospital, which involves the allocation of significant resources by the national health systems, not to speak of the inconvenience it entails for elderly subjects. Telemedicine can provide a partial solution to these problems. The present work describes a prototype system that transmits the patient`s electrocardiograms and the main characteristics of the pacemaker to a monitoring centre. This remote monitoring system will be beneficial to patients and health-care organizations in terms of quality of life for the former, and costs and efficiency for the latter.
Teleradiology in rural imaging centres
Authors: Davis Mark C
Published: October 2002

An economic analysis of a private commercial magnetic resonance MR imaging service was carried out. At an expected case-load of 2000 per year, a mid-field MR unit was predicted to cost 470 per case using teleradiology and 544 per case using film and a courier service. Routine and emergency MR services were provided to two communities in Maryland. In a two-year study period, 8083 teleradiology examinations were performed. Digital images were acquired and transmitted without data compression via ISDN at 128kbit s to a central diagnostic workstation for interpretation by a team of radiologists. The average transmission time for a typical case of 50 images was 6-8min. Preliminary interpretations were normally available within 2h and the final transcribed reports were usually faxed to the physicians` offices within 24h. The results of a survey indicated that the system was well received by both referring physicians and patients. Costs per case in practice were similar to those predicted.
The development of a telemedicine laboratory as a medical faculty resource
Authors: Brebner Eileen , Brebner J A , Ruddick-Bracken H , Norman J N
Published: October 2002

A telemedicine facility was established for the Faculty of Medicine of the University of Aberdeen and developed as a laboratory to help ensure a scientific approach to the implementation of telemedicine. Once a service application has been positively evaluated and established then it should be funded and delivered outside the laboratory, thus freeing up time and resources for the evaluation of new areas. Since it would appear that the practice of telemedicine is here to stay, it would also seem reasonable to suggest that an introduction to telemedicine should be included in the medical undergraduate curriculum.
Teledermatology—high technology or not?
Authors: Harrison P V , Kirby B , Dickinson Y , Schofield R
Published: October 2002

As an alternative to attending a conventional dermatology clinic, patients had a high-resolution conventional photographic image taken by a professional medical photographer. The photographic images were viewed by a dermatologist together with referral details from the general practitioner and any other relevant information from the patient's notes. From the images, a dermatological diagnosis was derived and a management plan for each patient instituted. After treatment, histological assessment of the tumours allowed diagnostic accuracy to be determined. The preliminary diagnostic accuracy (71%) was greater than that of the referring general practitioners (49%). However, when the diagnostic ability of the method to detect the nature of malignant lesions was examined, telemedicine was able to detect malignancies in 94% of cases compared with only 70% detected by general practitioners. The results of the present study indicate that teledermatology is achievable using a low-technology, low-cost approach.
Psychotherapy supervision conducted by videoconferencing: a qualitative study of users’ experiences
Authors: Gammon Deede , Sørlie Tore , Bergvik Svein , Høifødt Tordis Sørensen
Published: October 2002

Psychiatry residents in Norway have 70 hours of mandatory psychotherapy supervision to develop insights into the therapeutic relationship. Six supervision pairs (six candidates and two supervisors) conducted five videoconferencing-based supervision sessions (384kbit/s) and five face-to-face sessions alternating weekly for 10 sessions. Following completion of the 10 sessions for candidates and supervisor B, and the 50 sessions for supervisor A, all subjects completed a semi-structured interview within two weeks. The eight subjects reported a wide range of experiences and attitudes. The results suggested that the quality of supervision can be satisfactorily maintained by using videoconferencing for up to half of the 70 hours required. The precondition for this estimate is that the pair in question have met face to face and established a relationship characterized by mutual trust and respect. Further studies, which include supervision pairs not having previously established relationships, are needed in order to indicate the generality of this precondition. The most obvious implication of this study is the potential for implementing decentralized models for recruiting and educating psychiatrists.
An Internet station for telemedicine in the Azerbaijan Republic
Authors: Samedov R N
Published: October 2002

We have established the first medical Internet and telemedicine station in the Azerbaijan Republic. The station began work on 16 June 1997. In the next three months a list of local and international medical electronic resources was drawn up and contacts made with medical informatics organizations and medical libraries. Five telemedicine consultations were carried out with Moscow clinics in specialties such as cardiology, ophthalmology, endocrinology and surgery. The quickest and most cost-effective way of improving medical care in Azerbaijan is to provide medical information support using modern telecommunications.
Value of a low-cost telemedicine link in the remote echocardiographic diagnosis of congenital heart defects
Authors: Casey F , Brown D , Corrigan N , Craig B G , Quinn M , Mccord B , Rogers J , Mulholland H C
Published: October 2002

We established a low-cost telemedicine link from a district general hospital to the regional paediatric cardiology department about 120km away. The link was used to transmit echocardiographic images of newborn infants suspected of having congenital heart disease (CHD) to the referral centre, with simultaneous video and audio contact for consultation. Echocardiograms were transmitted for 61 patients suspected of having CHD, aged from 1 to 42 days. The transmitted images were of adequate quality for the paediatric cardiologist to make a diagnosis in 59 (97%). Congenital heart abnormalities were diagnosed in 38 (64%). Twelve patients (20%) had major CHD diagnosed on the transmitted scan and required transfer to the regional cardiology unit either urgently or electively after initial measures to stabilize the patient. Our findings suggest that, for babies suspected of having CHD, ultrasound images of diagnostic quality can be obtained and transmitted using a low-cost telemedicine system.
Hospice care using home-based telemedicine systems
Authors: Doolittle G C , Yaezel A , Otto F , Clemens C
Published: October 2002

A pilot study of telenursing for terminally ill patients at home was launched as a collaborative effort between KUMC and the Kendallwood Hospice. The service used the public telephone network. Interactive video equipment was installed in the homes of three nurses who received after-hours calls and in the homes of six hospice patients living in either Kansas or Missouri. Data concerning the utilization patterns were gathered for two separate three-month periods. Patients and caregivers reported general satisfaction with the telehospice system. Both the nurses and social worker providers became comfortable about video-calls. Nurses conducted video-assessments to determine whether an ‘in person’ visit was necessary. This was particularly helpful for rural patients who were living a long way from the base station. In addition, Kendallwood serves an urban population and, in certain areas, night-time nursing visits raise safety concerns.
The use of telemedicine to treat ophthalmological emergencies in rural Australia
Authors: Rosengren D , Blackwell N , Kelly G , Lenton L , Glastonbury J
Published: October 2002

A retrospective analysis was made of a cohort of patients who presented sequentially with acute ophthalmological conditions which were managed by telemedicine consultation. Twenty-four patients presented with acute problems requiring specialist ophthalmological advice to the emergency department of a remote hospital in Mt Isa, Queensland, between December 1996 and February 1997. Tele-ophthalmology consultations were carried out with three ophthalmologists working in a specialist eye clinic in Townsville, 900 km away. Patients and doctors were extremely positive about the telemedicine facility. Tele-ophthalmology was an effective means of providing acute specialist consultation in a remote emergency department. By reducing the need for acute transfers to the tertiary hospital in Townsville, significant benefits can be anticipated—both financial and in terms of convenience for the patient. Benefits for medical staff in skills acquisition and education were also evident.
Diagnostic accuracy and clinical management by realtime teledermatology. Results from the Northern Ireland arms of the UK Multicentre Teledermatology Trial
Authors: Loane M A , Corbett R , Bloomer S E , Eedy D J , Gore H E , Mathews C , Steele K , Wootton R
Published: October 2002

Diagnostic accuracy and management recommendations of realtime teledermatology consultations using low-cost telemedicine equipment were evaluated. Patients were seen by a dermatologist over a video-link and a diagnosis and treatment plan were recorded. This was followed by a face-to-face consultation on the same day to confirm the earlier diagnosis and management plan. A total of 351 patients with 427 diagnoses participated. Sixty-seven per cent of the diagnoses made over the video-link agreed with the face-to-face diagnosis. Clinical management plans were recorded for 214 patients with 252 diagnoses. For this cohort, 44 of the patients were seen by the same dermatologist at both consultations, while 56 were seen by a different dermatologist. In 64 of cases the same management plan was recommended at both consultations; a sub-optimum treatment plan was recommended in 8 of cases; and in 9 of cases the video-link management plans were judged to be inappropriate. In 20 of cases the dermatologist was unable to recommend a suitable management plan by video-link. There were significant differences in the ability to recommend an optimum management plan by video-link when a different dermatologist made the reference management plan. The results indicate that a high proportion of dermatological conditions can be successfully managed by realtime teledermatology.
Telemedicine and the organization of the health sector
Authors: Aas I H Monrad
Published: October 2002

The widespread introduction of telemedicine would have organizational consequences for the health sector. However, the problem of health-sector organization is complex. A general frame work for analysis of organizational consequences has been developed and consists of eight points. These are: (1) the starting point; (2) mapping of applications of telemedicine where organizational consequences are possible; (3) characterizing the nature of larger organizational consequences; (4) the consequences for the health sector in the chosen area; (5) possible consequences for the number and placement of geographical subunits of the health sector; (6) possible consequences for health sector organizational types; (7) the consequences for the tools of health policy; and (8) design of the change process towards a new organization.
The North Norwegian Health Net
Authors: Pettersen Sture , Uldal Siri Birgitte , Baardsgard Anders , Amundsen Morten , Myrvang Robert , Nordvåg Dag , Stenmarkl Håvar
Published: October 2002

The North Norwegian Health Net is a comprehensive scheme to connect all health-care institutions in the area to a national computer network. Services available include telemedicine, email and Web access. A general practitioner has responsibility for ensuring that the clinical information is correct. Medical departments are responsible for the content of their own Web pages. All institutions require authorization before connection to ensure data protection and security. Changes in communication between primary- and secondary-care sectors are being monitored. To date the implementation of the network programme has gone smoothly.
Low-cost ISDN videoconferencing equipment for orthopaedic second opinions
Authors: Baruffaldi F , Mattioli P , Toni A , Klutke P J , Englmeier K H
Published: October 2002

We validated the application of low-cost ISDN videoconferencing equipment for telemedicine. A telemedicine benchmark was designed and four different office video conferencing systems were evaluated, all using basic-rate ISDN connections (128 kbit/s). All the low-cost systems showed generally good or acceptable performance for clinical use. We also investigated the feasibility of videoconferencing for an orthopaedic second-opinion service. Eight point-to-point conferences were conducted to discuss real clinical cases by use of interactive sharing of medical images. The average duration of each session was 35 min. Encouraging results were obtained.
Sigmoidoscopy in a nurse-practitioner community clinic using telemedicine
Authors: Wan A C T , Taylor P , Gul Y , Taffinder N J , Gould S W T , Darzi A
Published: October 2002

We evaluated the feasibility of remote endoscopy in a community setting Realtime teleconsultation and telesigmoidoscopy were carried out by a nurse practitioner at a community clinic while a colorectal specialist was present at the main hospital. Rigid video-sigmoidoscopes were used and the images were transmitted via ISDN lines at 384 kbit/s. Over three months, 32 patients (mean age 35 years; 19 men and 13 women) with bleeding per rectum took part in the study. Evaluation was carried out using satisfaction questionnaires for the patients, the nurse practitioner and the clinicians. The mean grade for clarity of intraluminal views was 3.5 (1 poor, 4 excellent). Only two cases had views graded less than 3, due to the presence of excessive faecal residue. All the patients were satisfied with the teleconsultation and video-endoscopy and would return for a similar visit. User satisfaction was also high on the part of the nurse practitioner and the clinician.
Low-bandwidth tele-ultrasound
Authors: Brebner John A , Ruddick-Bracken H , Brebner Eileen M , Gilbert Fiona J , Maclean J R , Ritchie L D R , Smith P , Thompson A
Published: October 2002

We examined the acceptability and diagnostic accuracy of dynamic ultrasound images transmitted at 128 kbit/s and 384 kbit/s. The gold standard was the direct recording of 200 ultrasound examinations on video-tape. The taped images were later transmitted at both 128 kbit/s and 384 kbit/s and recorded, resulting in three tapes for each case. Four observers viewed each tape individually. Ninety per cent of images transmitted at 384 kbit/s were rated as diagnostically acceptable compared with 32% of images transmitted at 128 kbit/s. Diagnostic agreement between tapes transmitted at 384 kbit/s and the gold standard was 85%, compared with 78% for 128 kbit/s transmissions. Observers were not satisfied with low-bandwidth transmission of ultrasound images despite adequate diagnostic accuracy. Dynamic ultrasound images transmitted at 384 kbit/s were viewed as both diagnostically acceptable and accurate.
The legal implications of veterinary telemedicine and telecare
Authors: Jack Douglas C
Published: October 2002

This paper presents an overview of some legal implications of the application of telemedicine to veterinary medicine. As in other areas of medicine, veterinary practitioners need to be aware that remote practice or consultation requires adherence to the same professional standards as in normal clinical veterinary practice. Licensing, confidentiality and malpractice are discussed.
An assessment framework for telemedicine applications
Authors: Hailey D , Jacobs P , Simpson J , Doze S
Published: October 2002

Pressures for the adoption of telemedicine place increased demands on purchasers to assess applications of the technique. Assessment principles are helpful in defining an evaluation framework for use at the local level. We suggest an assessment approach that includes five specific elements: specification; performance measures; outcomes; summary measures; and operational and other considerations. The approach described here was developed to assist with the needs of individual health authorities and institutions within the health-care system of Alberta. Aspects of the approach are illustrated using a telepsychiatry example under the assumptions made. Conventional psychiatry (where the patient visited the psychiatrist) was most expensive for the patient. The alternatives, telepsychiatry and outreach psychiatry (where the psychiatrist travelled to the patient), cost about the same from the service provider's perspective (and from that of society as a whole); they were both much cheaper for the patient. At higher volumes, telepsychiatry would be cheaper than outreach.
Minimum requirements for remote realtime fetal tele-ultrasound consultation
Authors: Chan F Y , Whitehall J , Hayes L , Taylor A , Soong B , Lessing K , Cincotta R , Cooper D , Stone M , Lee-Tannock A , Baker S , Smith M , Green E , Whiting R
Published: October 2002

We studied the transmission bandwidth required for accurate diagnoses when performing realtime fetal tele-ultrasound consultations. The study was divided into three phases. In phase I, three experienced clinicians evaluated the quality of ultrasound images transmitted at various bandwidths (internally looped back within Brisbane) using eight commercially available codecs at random. The two codecs that performed best proceeded to phase 2, in which a realtime video-link of up to 2Mbit/s was set up between Brisbane and Townsville (1500 km apart). Testing with a standard video-tape was performed at seven different bandwidths selected at random, with four clinicians (who were blinded to the equipment and bandwidths used). The optimum line rates for transmission were determined, and testing was then performed using these line rates for fetuses with various anomalies (phase 3). The results showed significant differences in performance according to bandwidths used, but not according to observers. Bandwidths were grouped into three levels. At level I (256 kbit/s) the performance was significantly worse than at level II (384, 512 or 768 kbit/s), which was in turn worse than that at level III (1, 1.5 or 2Mbit/s). However, within each level, performance at one bandwidth was not significantly different from that at the others. The most cost-effective transmission rates therefore appeared to be 384kbit/s and 1Mbit/s. Further testing with fetuses affected by various anomalies confirmed that the majority could be diagnosed using a 384 kbit/s link, with slight improvement in evaluation when the bandwidth was increased to 1 Mbit/s.
Equipment for minor injuries telemedicine
Authors: Wootton Richard
Published: October 2002

A telemedicine system for minor injuries work comprises two main components: (1) a face-to-face videoconferencing system, often including a second camera at the patient end for close-up pictures; and (2)a system for the transmission and display of radiographic images (i.e. teleradiology). There is a wide variety of equipment being used for minor injuries telemedicine in the UK. For videoconferencing, low-cost systems—including those based on PCs—and medium-cost systems are in use. For teleradiology, high-resolution systems (i.e. those complying with the standard set by the American College of Radiology) and low-resolution systems (i.e. those which do not) are in use. The quality of the telemedicine interaction for minor injuries work therefore appears to be less dependent on the sophistication of the equipment used than on other factors, including human ones. Equipment choice has implications for costs.
Use of telemedicine in undergraduate teaching of surgery
Authors: Gul Y A , Wan A C T , Darzi A
Published: October 2002

Telemedicine as an undergraduate teaching method was evaluated by exposing medical students to outpatient videoconferencing. Forty clinical students on a 10-week surgical rotation participated in the study. Telemedicine sessions involved videoconferencing from the general surgical outpatient department located in a sister hospital 8 km away, using a roll-about system connected by ISDN at 384 kbit/s. A questionnaire was used to assess the quality of time spent and educational information obtained by the students. On a scale of 0-10, the students gave an overall rating of 9.7 for outpatient teaching using telemedicine. All 40 students indicated a willingness to return for similar teaching sessions. Even though the results were encouraging, an objective assessment of the knowledge gained by the students is required before the inclusion of this teaching technique in an existing medical curriculum can be recommended unequivocally.
Application of inter–simple sequence repeat PCR to mouse models: Assessment of genetic alterations in carcinogenesis
Authors: Benavides Fernando , Zamisch Mónica , Flores Mónica , Campbell Marcia R. , Andrew Susan E. , Angel Joe M. , Licchesi Julien , Sternik Gabriel , Richie Ellen R. , Conti Claudio J.
Published: October 2002

Genomic instability is believed to play a significant role in cancer development by facilitating tumor progression and tumor heterogeneity. Inter–simple sequence repeat (inter‐SSR) PCR has been proved to be a fast and reproducible technique for quantitation of genomic instability (amplifications, deletions, translocations, and insertions) in human sporadic tumors. However, the use of inter‐SSR PCR in animal models of cancer has never been described. This new technique has been adapted in our laboratory for the analysis of spontaneous and induced mouse tumors. We established the best PCR conditions for each microsatellite‐anchored primer and critically evaluated the reproducibility of the band patterns. We also studied the variation of the fingerprints between and within various inbred mouse strains, including wild‐derived lines. Tumor‐specific alterations were detected as gains, losses, or intensity changes in bands when compared with matched normal DNA. We quantitated the extent of alterations by dividing the number of altered bands in the tumor by the total number of bands in normal DNA (instability index). By means of inter‐SSR PCR, we successfully analyzed genomic alterations in various mouse tumors, including spontaneous thymic lymphomas developed in Msh2 knockout mice as well as chemically induced squamous cell carcinomas and thymic lymphomas. Instability index values ranged between 0 and 9%, the highest levels observed in N‐methyl‐N‐nitrosourea–induced thymic lymphomas generated in Trp53 (p53) nullizygote (−/−) mice. We report here, for the first time, the use of inter‐SSR PCR to detect somatic mutations in mouse tumoral DNA, including laser‐capture microdissected, methanol‐fixed tissues. These PCR‐based fingerprints provide a novel approach to assessing the number and onset of mutational events in mouse tumors and will help to understand better the mechanisms of carcinogenesis in mouse models. © 2002 Wiley‐Liss, Inc.
Terminal α‐linked galactose rather than N‐acetyl lactosamine is ligand for bovine heart galectin‐1 in N‐linked oligosaccharides of glycoproteins
Authors: Appukuttan P. S.
Published: October 2002

Preference for the β‐anomer of galactose attributed to the bovine heart 14 kDa galectin‐1 (BHL‐14) was re‐examined using natural glycoproteins and artificially glycosylated proteins as ligands. Endogenous glycoproteins co‐purified with BHL‐14 during its affinity chromatographic isolation contained oligosaccharides bearing terminal α‐linked galactose (TAG) moieties and were superior even to laminin as ligands for homogeneous BHL‐14 obtained by high pressure liquid chromatography. Artificially glycosylated proteins prepared by covalent attachment of melibiose to proteins and containing TAG moieties were ligands for BHL‐14, unlike their lactose counterparts which contained β‐linked galactose. Enzymatic removal of TAG moieties from the following glycoproteins abolished their recognition by BHL‐14: (i) endogenous glycoproteins co‐purified with BHL‐14; (ii) mouse laminin; and (iii) bovine heart glycoproteins recognized by peanut agglutinin. Modification of TAG in laminin using galactose oxidase also rendered the glycoprotein inert towards BHL‐14. Desialylation of human IgG, bovine thyroglobulin or laminin failed to increase the affinity of BHL‐14 for these glycoproteins. Since removal of TAG or of sialic acid moiety exposed LacNAc (Gal β1→4 GlcNAc) in these glycoproteins, these results indicated that TAG, rather than LacNAc, is a ligand for BHL‐14 on N‐linked oligosaccharide chains of glycoproteins. Ready recognition of human IgA and jacalin‐binding human plasma glycoproteins and non‐recognition of human IgG suggested that T antigen (Galβ1→3 GalNAc) may also be ligand for galectin‐1. Copyright © 2002 John Wiley & Sons, Ltd.
Computerised morphometric study of the paraurethral tissue in young and elderly women
Authors: Verelst M. , Maltau J.M. , Ørbo A.
Published: October 2002

Aim.

Changes in structural support of the urethra and bladder neck have been proposed to be among the most important factors in the pathogenesis of stress urinary incontinence. In this context, we histologically investigated the paraurethral area in continent women to quantify the relative distribution of connective tissue, smooth muscle, vessels, nerves, and striated muscle. Previously published literature gives only descriptive evaluations of the relative distribution of these tissue components.

Methods.

We used a computerised morphometric method, which allowed us to estimate the paraurethral tissue distribution in a more objective way. The material was obtained by dissection during autopsy in five premenopausal and five postmenopausal women.

Results.

Paraurethral tissue consisted of 56% connective tissue (SD, 5%), 30% smooth muscle (SD, 5%), 11% blood vessel (SD, 6%), 2% striated muscle (SD, 3%), and 1% nerves (SD, 1%). We also found that the distribution of different tissue components along the length of the urethra did not differ at a statistically significant level. Furthermore, there was a statistically significant difference in the amount of connective tissue and blood vessels in the postmenopausal women compared with the premenopausal women.

Conclusions.

The present study shows that the paraurethral area is built of heterogeneous tissue with small changes in its composition along the course of urethra. Increase in connective tissue was found to be the dominating change in the process of ageing. Neurourol. Urodynam. 21:529–533, 2002. © 2002 Wiley‐Liss, Inc.
Molecular screens for inner ear genes
Authors: Heller Stefan
Published: October 2002

Identification of the genes that encode proteins that are important for proper function of specific inner ear cell types is central to our understanding of the molecular basis of hearing and balance. Whereas the combination of electrophysiology and biophysics has resulted in an exquisite understanding of inner ear function, little is known about the proteins that confer these properties at the cellular level. Furthermore, the genes that control inner ear development, susceptibility to wear and tear, regeneration from damage, and age‐related degeneration, are largely unknown. This review discusses tools that have been developed during the past few years to address this imbalance between a thorough physiologic characterization of inner ear function and a detailed understanding at a molecular level of the proteins involved in these functions. Creation of inner ear cDNA libraries has laid the foundation for the discovery of genes that are specifically expressed by cell types of the inner ear and that encode proteins that are important for molecular processes in these cells. In conjunction with expressed sequence tag database analysis, cDNA subtraction, and DNA arrays, functionally important genes, whose specific expression patterns are usually verified by gene expression analysis, can be identified. Discussion of these techniques takes into account the specific characteristics of the inner ear in relation to its study using molecular biological approaches. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 265–275, 2002
Melanization ofCryptococcus neoformansandHistoplasma capsulatumReduces Their Susceptibilities to Amphotericin B and Caspofungin
Authors: van Duin David , Casadevall Arturo , Nosanchuk Joshua D.
Published: October 2002

The fungal pathogensCryptococcus neoformansandHistoplasma capsulatumproduce melanin-like pigments in the presence ofl-dopa in vitro and during mammalian infection. We investigated whether melanization affected the susceptibilities of the fungi to amphotericin B, caspofungin, fluconazole, itraconazole, or flucytosine (5FC). Using the standard macrodilution MIC protocol (the M27A protocol) of the National Committee for Clinical Laboratory Standards for yeast, we found no difference in the susceptibilities of melanized and nonmelanizedC. neoformansandH. capsulatumisolates. Killing assays demonstrated that melanization reduced the susceptibilities of both fungi to amphotericin B and caspofungin. Laccase-deficientC. neoformanscells grown withl-dopa were significantly more susceptible than congenic melanin-producing yeast to killing by amphotericin B or caspofungin. Preincubation of amphotericin B or caspofungin with melanins decreased their antifungal activities. Elemental analysis of melanins incubated with amphotericin B or caspofungin revealed an alteration in the C:N ratios of the melanins, which indicated binding of these drugs by the melanins. In contrast, incubation of fluconazole, itraconazole, or 5FC with melanins did not significantly affect the antifungal efficacies of the drugs or the chemical composition of the melanins. The results suggest a potential explanation for the inefficacy of caspofungin againstC. neoformansin vivo, despite activity in vitro. Furthermore, the results indicate that fungal melanins protectC. neoformansandH. capsulatumfrom the activities of amphotericin B and caspofungin and that this protection is not demonstrable by standard broth macrodilution assays.
Evaluation of Differential Gene Expression in Fluconazole-Susceptible and -Resistant Isolates of
Candida albicans
by cDNA Microarray Analysis
Authors: Rogers P. David , Barker Katherine S.
Published: October 2002

The opportunistic fungal pathogen
Candida albicans
is the major causative agent of oropharyngeal candidiasis (OPC) in AIDS. The development of azoles, such as fluconazole, for the treatment of OPC has proven effective except in cases where
C. albicans
develops resistance to fluconazole during the course of treatment. In the present study, we used microarray technology to examine differences in gene expression from a fluconazole-susceptible and a fluconazole-resistant well-characterized, clinically obtained matched set of
C. albicans
isolates to identify genes which are differentially expressed in association with azole resistance. Among genes found to be differentially expressed were those involved in amino acid and carbohydrate metabolism; cell stress, cell wall maintenance; lipid, fatty acid, and sterol metabolism; and small molecule transport. In addition to
CDR1
, which has previously been demonstrated to be associated with azole resistance, the drug resistance gene
RTA3
, the ergosterol biosynthesis gene
ERG2
, and the cell stress genes
CRD2
,
GPX1
, and
IFD5
were found to be upregulated. Several genes, such as the mitochondrial aldehyde dehydrogenase gene
ALD5
, the glycosylphosphatidylinositol synthesis gene
GPI1
, and the iron transport genes
FET34
and
FTR2
were found to be downregulated. Further study of these differentially regulated genes is warranted to evaluate how they may be involved in azole resistance. In addition to these novel findings, we demonstrate the utility of microarray analysis for studying the molecular mechanisms of drug resistance in pathogenic organisms.
In Vivo Toxicity, Pharmacokinetics, and Anti-Human Immunodeficiency Virus Activity of Stavudine-5′-(p-Bromophenyl Methoxyalaninyl Phosphate) (Stampidine) in Mice
Authors: Uckun Fatih M. , Qazi Sanjive , Pendergrass Sharon , Lisowski Elizabeth , Waurzyniak Barbara , Chen Chun-Lin , Venkatachalam T. K.
Published: October 2002

We have evaluated the clinical potential of stavudine-5′-(p-bromophenyl methoxyalaninyl phosphate(stampidine [STAMP]), a novel aryl phosphate derivative of stavudine, as a new anti-human immunodeficiency virus (anti-HIV) agent, by examining its acute, subacute, and chronic toxicity profile in mice as well as by testing its antiviral activity in a surrogate human peripheral blood lymphocyte (Hu-PBL)-SCID mouse model of human AIDS. STAMP was very well tolerated in BALB/c and CD-1 mice, without any detectable acute or subacute toxicity at single intraperitoneal or oral bolus doses as high as 500 mg/kg of body weight. Notably, daily administration of STAMP intraperitoneally or orally for up to 8 consecutive weeks was not associated with any detectable toxicity at cumulative dose levels as high as 6.4 g/kg. Micromolar concentrations of the active STAMP metabolite in plasma were rapidly achieved and maintained for more than 4 h after parenteral as well as oral administration of a nontoxic 100-mg/kg bolus dose of STAMP. In accordance with its favorable pharmacokinetic profile and in vitro potency, STAMP exhibited dose-dependent and potent in vivo anti-HIV activity in Hu-PBL-SCID mice against a genotypically and phenotypically nucleoside analog reverse transcriptase inhibitor (NRTI)-resistant clinical HIV type 1 (HIV-1) isolate (BR/92/019; D67N, L214F, T215D, K219Q) at nontoxic dose levels. The remarkable in vivo safety and potency of STAMP warrants the further development of this promising new antiretroviral agent for possible clinical use in patients harboring NRTI-resistant HIV-1.
Antimicrobial Therapy forBacillus anthracis-Induced Polymicrobial Infection in60Co γ-Irradiated Mice
Authors: Elliott Thomas B. , Brook Itzhak , Harding Rita A. , Bouhaouala S. Samy , Shoemaker Michael O. , Knudson Gregory B.
Published: October 2002

Challenge with both nonlethal ionizing radiation and toxigenicBacillus anthracisspores increases the rate of mortality from a mixed bacterial infection. If biological weapons, such asB. anthracisspores, and nuclear weapons were used together, casualties could be more severe than they would be from the use of either weapon alone. We previously discovered that a polymicrobial infection developed in B6D2F1/J mice after nonlethal (7-Gy)60Co γ irradiation and intratracheal challenge withB. anthracisSterne spores 4 days after irradiation. In this present study, we investigated the survival of mice and the response of the polymicrobial infection during the course of antimicrobial therapy with penicillin G procaine, ofloxacin, trovafloxacin, or gatifloxacin. Survival was prolonged, but not ensured, when the mice were treated with either broad-spectrum ofloxacin or narrow-spectrum penicillin G for 7 days beginning 6 or 24 h after challenge. Survival was not prolonged when therapy was delayed more than 24 h after challenge. When these two antimicrobial agents were given for 21 days, the survival rate was increased from 0% for the controls to 38 to 63% after therapy. Therapy with trovafloxacin or gatifloxacin reduced the incidence of mixed infection and improved the rate of survival to 95% (trovafloxacin) or 79% (gatifloxacin), whereas the rate of survival for the controls was 5%. We conclude that the mixed infection induced byB. anthracisin irradiated mice complicates effective therapy with a single antimicrobial agent. To limit mortality following nonlethal irradiation and challenge withB. anthracisspores, antimicrobial therapy needs to be initiated within a few hours after challenge and continued for up to 21 days.
Chromosome-Encoded β-Lactamases TUS-1 and MUS-1 from
Myroides odoratus
and
Myroides odoratimimus
(Formerly
Flavobacterium odoratum
), New Members of the Lineage of Molecular Subclass B1 Metalloenzymes
Authors: Mammeri Hedi , Bellais Samuel , Nordmann Patrice
Published: October 2002

Myroides odoratus
and
Myroides odoratimimus
(formerly designated in a single species as
Flavobacterium odoratum
) are gram-negative aerobes and sources of nosocomial infections in humans. They have variable susceptibility to β-lactams and a decreased susceptibility to carbapenems. Using genomic DNAs of
M. odoratus
CIP 103105 and
M. odoratimimus
CIP 103073 reference strains, shotgun cloning of β-lactamase genes was performed, followed by protein expression in
Escherichia coli
. The deduced amino acid sequences of these β-lactamase genes revealed that TUS-1 and MUS-1 from
M. odoratus
CIP 103105 and
M. odoratimimus
CIP 103073, respectively, shared 73% amino acid identity. Mature proteins TUS-1 and MUS-1, with pI values of 7.8 and 5.2, respectively, had relative molecular masses of ca. 26 kDa. These β-lactamases are members of the subclass B1 of metallo-β-lactamases and are distantly related to other metalloenzymes, being most closely related to IND-1 from
Chryseobacterium indologenes
(42% amino acid identity). However, phylogenic analysis showed that TUS-1 and MUS-1 belong to the same phylogenic lineage of subclass B1 enzymes that groups the subclass B1 β-lactamases of
Flavobacterium
species. Kinetic parameters of purified β-lactamases TUS-1 and MUS-1 detailed their hydrolysis spectra, which encompass most β-lactams except aztreonam. β-Lactamases TUS-1 and MUS-1 were classified in functional subgroup 3a of metalloenzymes. This work further characterizes chromosome-encoded metalloenzymes from
Flavobacteriaceae
species that explain at least part of their intrinsic resistance to β-lactams.
Feasibility modeling of passive soil vapor extraction
Authors: Jennings A A , Patil P
Published: October 2002

Passive soil vapor extraction (PSVE) is a soil remediation process that uses ambient meteorological conditions to accomplish gas well pumping. Passive soil vapor extraction wells use simple unpowered wellheads in place of vacuum pumps or blowers. They can be used for extraction or injection pumping and can reduce the complexity and cost of either. The innate "pulse-pumping" pattern of PSVE may also help overcome mass transfer resistances within the soil. However, the meteorological conditions that drive PSVE are strongly random in magnitude and duration and produce flows that are lower than pumped soil vapor extraction (SVE). Although PSVE had been successfully field demonstrated, uncertainty about well yields and design procedures has hindered application. This manuscript presents the results of PSVE feasibility modeling. Analysis is presented to illustrate that, under appropriate conditions, PSVE can yield useful well flows. Transient gas flow analysis is required to account for meteorological boundary conditions that impact the domain on relatively fine time scales. Analysis is also presented to illustrate the impacts that non-steady flow conditions can have on contaminant mass transport. Results show that under appropriate conditions PSVE could be competitive with conventional pumped vapor extraction. Extraction rates will be lower, but may be achieved at significantly lower cost. Key words: vapor extraction, remediation, passive pumping, mass transport modeling, transient boundary conditions, feasibility analysis.
A body-condition index for ursids
Authors: Cattet Marc R.L , Caulkett Nigel A , Obbard Martyn E , Stenhouse Gordon B
Published: October 2002

In this investigation a body-condition index (BCI) was developed for polar bears (Ursus maritimus), black bears (Ursus americanus), and grizzly bears (Ursus arctos), based on residuals from the regression of total body mass against a linear measure of size, straight-line body length (SLBL). Transformation of masslength data from 1198 polar bears, 595 black bears, and 126 grizzly bears to natural logarithms resulted in a linear relationship between mass and length. However, the relationship in polar bears differed from that in black and grizzly bears. SLBL had a close positive relationship with skeletal (bone) mass in polar bears (n = 31) and black bears (n = 33), validating the use of SLBL as an accurate index of body size. There was no correlation between SLBL and BCI for polar bears (r = 0.005, p = 0.87, n = 1198) or for black bears and grizzly bears (r = 0.04, p = 0.30, n = 721), indicating that the BCI was independent of body size. The BCI had a close positive relationship with true body condition, measured as the standardized residual of the combined mass of fat and skeletal muscle against SLBL, in polar and black bears that were dissected to determine individual tissue masses. The BCI also had a close positive relationship with the standardized residual of fat mass against SLBL. Estimation of BCI values for polar bears, or for black bears and grizzly bears, is facilitated by prediction equations that require measurement of total body mass and SLBL for individual animals.
COMPLEXITY OF SCENARIO-BASED PORTFOLIO OPTIMIZATION PROBLEM WITH VaR OBJECTIVE
Authors: YANG XIAOGUANG , TAO SHUO , LIU RONGJUN , CAI MAOCHENG
Published: October 2002

In this paper we discuss the VaR-related portfolio optimization problems. We give a scenario-based formulation of the portfolio optimization problem with VaR objective and show that the problem is NP-hard.
APPROXIMATION ALGORITHMS FOR LOCAL ALIGNMENT WITH LENGTH CONSTRAINTS
Authors: Arslan Abdullah N. , Eğecioğlu Ömer
Published: October 2002

The local sequence alignment problem is the detection of similar subsequences in two given sequences of lengths n ≥ m. Unfortunately the common notion of local alignment suffers from some well-known anomalies which result from not taking into account the lengths of the aligned subsequences. We introduce the length restricted local alignment problem which includes as a constraint an upper limit T on the length of one of the subsequences to be aligned. Obvious extensions of dynamic programming formulations for the solution of the length restricted local alignment problem result in expensive computations: O(Tnm) time and O(Tm) space. We propose an efficient approximation algorithm using which we can find a solution satisfying the length bound, and whose score is within difference Δ of the optimum score for any given positive integer Δ in time O(nmT/Δ) using O(mT/Δ) space. We also introduce the cyclic local alignment problem and show how our idea can be applied to this case as well. This is a dual approach to the well-known cyclic edit distance problem. These results generalize directly to the case of affine gap penalties.
Fixed point theorems for densifying mappings and compact mappings
Authors: Liu Zeqing , Wang Li , Kang Shin Min , Kim Yong Soo
Published: October 2002

The purpose of this note is to establish fixed point theorems for densifying mappings and compact mappings which are contractive in metric spaces and to investigate the existence of fixed points for a family of mappings in bounded metric spaces. The results of this note generalize the results of Bailey (1966) and Liu (1994).