Biomedical subjects
Publications and source records attributed to R Martinez.
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DR-nm23 cDNA was cloned recently by differential screening of a cDNA library derived from chronic myelogenous leukemia-blast crisis primary cells. It is highly homologous to the putative metastasis suppressor nm23-H1 gene and the closely related nm23-H2 gene. When overexpressed in the myeloid precursor 32Dcl3 cell line, it inhibited granulocyte colony-stimulating factor-stimulated granulocytic differentiation and induced apoptosis. We have now found that the expression of DR-nm23 is not restricted to hematopoietic cells but is also detected in an array of solid tumor cell lines, including carcinoma of the breast, colon, and prostate, as well as the glioblastoma cell line T98G. We have also isolated both the gene and its 5'-flanking region and found that DR-nm23 localizes on chromosome 16q13. The gene consists of six exons and five introns. When fused in-frame to the nucleotide sequence for the green fluorescent protein and transfected in SAOS-2 cells, it generates a protein of the predicted size that localizes to the cytoplasm. The 5'-flanking region of DR-nm23 does not contain a canonical TATA box or a CAAT box, but it is G+C rich and contains two binding sites for the developmentally regulated transcription factor activator protein 2 (AP-2). Transient expression assays of DR-nm23 promoter-chloramphenicol acetyltransferase constructs demonstrated that the segment from nucleotides -1028 to +123 has the highest activity in hematopoietic K562 cells and in TK-ts13 hamster fibroblasts. Moreover, AP-2 induced a 3-fold transactivation of the DR-nm23 5'-flanking segment from nucleotides -1676 to +123 and interacted specifically with oligomers containing putative AP-2 binding sites (-936 to -909, and -548 to -519) as indicated by electrophoretic mobility shift assay. Furthermore, nuclear run-on assays from high and low DR-nm23-expressing cells (K562 and CCRF-CEM, respectively) revealed similar transcription rates. Therefore, the regulation of the DR-nm23 gene expression might involve other mechanisms occurring at posttranscriptional and/or translational levels.
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Receptor protein tyrosine phosphatase beta (RPTPbeta) expressed on the surface of glial cells binds to the glycosylphosphatidylinositol (GPI)-anchored recognition molecule contactin on neuronal cells leading to neurite outgrowth. We describe the cloning of a novel contactin-associated transmembrane receptor (p190/Caspr) containing a mosaic of domains implicated in protein-protein interactions. The extracellular domain of Caspr contains a neurophilin/coagulation factor homology domain, a region related to fibrinogen beta/gamma, epidermal growth factor-like repeats, neurexin motifs as well as unique PGY repeats found in a molluscan adhesive protein. The cytoplasmic domain of Caspr contains a proline-rich sequence capable of binding to a subclass of SH3 domains of signaling molecules. Caspr and contactin exist as a complex in rat brain and are bound to each other by means of lateral (cis) interactions in the plasma membrane. We propose that Caspr may function as a signaling component of contactin, enabling recruitment and activation of intracellular signaling pathways in neurons. The binding of RPTPbeta to the contactin-Caspr complex could provide a mechanism for cell-cell communication between glial cells and neurons during development.
The central anticholinergic drug scopolamine has been used to model aspects of the memory impairment that occurs in Alzheimer's disease and in aging. To determine whether nonspecific stimulant effects can attenuate the cognitive impairment induced by scopolamine, we studied the effects of scopolamine and the stimulant dextroamphetamine in 17 young normal volunteers. After a baseline day of cognitive testing, subjects participated in two study days, in which they received dextroamphetamine (d-AMP) (0.25 mg/kg p.o.) + scopolamine (0.5 mg i.v.) and placebo + scopolamine, in randomized order under double-blind conditions. There were no statistically significant differences in cognitive test performance between the two drug conditions with the exception of one of the category retrieval tasks. Stimulant effects were documented to occur by other measures. We conclude that d-AMP at the dose used does not attenuate the memory impairment induced by scopolamine.
Sixty-one patients who had lumbar instability and chronic low back pain or deformity from nontraumatic lumbar pathologies were studied. In all of them a posterior lumbosacral fusion with CUN (Clinic of the University of Navarre) pedicle rod fixation was used. The mean follow-up period was 36 months (range 26-46 months). The consolidation rate was evaluated according to plain and functional radiographs, and a clinical evaluation was made using an analogue pain scale. The rate of fusion was 93.5%. Neurological complications occurred in 3.3%. The incidence of screw failure was 2.3% of all the screws. No other implant failure occurred. The patients rated their clinical results as 'excellent' in 33.8% of the cases, 'good' in 42.2%, 'fair' in 16.9% and 'poor' in 6.7%. CUN instrumentation is a versatile internal fixation system that has been shown to provide satisfactory stability. Furthermore, the clinical results are comparable to those reported in studies in which the most common hardwares were used.
Cerebrovascular disease exemplifies the poor regenerative capacity of the CNS. While there are methods to prevent cerebral infarction, there is no effective therapy available to ameliorate the anatomical, neurochemical and behavioral deficits which follow cerebral ischemia. Focal and transient occlusion of the middle cerebral artery (MCA) in rodents has been reported to result in neuropathology similar to that seen in clinical cerebral ischemia. Using specific techniques, this MCA occlusion can result in a well-localized infarct of the striatum. This review article will provide data accumulated from animal studies using the MCA occlusion technique in rodents to examine whether neural transplantation can ameliorate behavioral and morphological deficits associated with cerebral infarction. Recent advances in neural transplantation as a treatment modality for neurodegenerative disorders such as Parkinson's disease, have revealed that fetal tissue transplantation may produce neurobehavioral recovery. Accordingly, fetal tissue transplantation may provide a potential therapy for cerebral infarction. Preliminary findings in rodents subjected to unilateral MCA occlusion, and subsequently transplanted with fetal striatal tissue into the infarcted striatum have produced encouraging results. Transplanted fetal tissue, assessed immunohistochemically, has been demonstrated to survive and integrate with the host tissue, and, more importantly, ameliorate the ischemia-related behavioral deficits, at least in the short term. Although, this review will focus primarily on cerebral ischemia, characterized by a localized CNS lesion within the striatum, it is envisioned that this baseline data may be extrapolated and applied to cerebral infarction in other brain areas.
Static-image and dynamic- (real-time) image telepathology are competing technologies. Although some studies suggest that the diagnostic accuracy of the dynamic-image telepathology approaches the accuracy of light microscopy, few reports have documented the diagnostic accuracy of static-image telepathology as used in the setting of an actual surgical pathology consultation practice. We report the results of an analysis of 171 telepathology consultation cases submitted to the Arizona-International Telemedicine Network (AITN). Digital images were submitted by pathologists from six participating institutions in Arizona, Mexico, and China. Telepathologists could render a telepathology diagnosis (TP) or defer rendering a diagnosis to obtain additional video images, glass slides for detailed analysis, or to obtain tissue blocks for special studies such as immunohistochemistry. The telepathologists rendered diagnoses for 144 cases and deferred 27 cases. Two pathologists retrospectively evaluated-glass slides from each case and rendered a consensus glass slide (GS) "truth" diagnosis. There was 88.2% concordance between TP and GS diagnoses (127 of 144 diagnoses). Concordance of 96.5% was achieved for clinically important diagnoses (139 of 144 diagnoses). Telepathologists deferred making a diagnosis to obtain glass slides for conventional light microscopy in 14 cases (8.1%) and for results of immunohistochemistry studies in 13 cases (7.6%). Thus, correct diagnoses were rendered by static-image telepathology in 127 of 171 cases (74.3%) at the time of telepathology diagnostic sessions. Inappropriate field selection and sampling biases of referring pathologists, as well as a tendency of static-image telepathologists to underestimate the complexity of some cases, may reduce the value of consultations based on the viewing of static images.
The purpose of this study was to investigate the cognitive and behavioral effects of anticholinergic, antidopaminergic, and antiserotonergic agents given alone and in combination to normal volunteers. Twelve young male volunteers took part in this double-blind, randomized, placebo-controlled, crossover study of six drug conditions, each administered on separate days [haloperidol (2 mg p.o.) +/-scopolamine (0.5 mg i.v.), metergoline (4 mg p.o.) +/-scopolamine (0.5 mg i.v.), placebo, and scopolamine alone (0.5 mg i.v.)]. Scopolamine-induced sedation (p < .01), slowed information processing (p < .01) and impaired new learning and memory (p < .01), but did not affect attention or retrieval from semantic memory. Given alone, haloperidol selectively impaired the ability to rapidly switch cognitive sets (p < .05), and metergoline decreased pupil size (p < .01) but did not induce cognitive deficits. In combination with scopolamine, neither haloperidol nor metergoline produced a worsening of the subjects' cognitive performance above and beyond that seen with scopolamine alone. On the contrary, a trend (p < .10) for haloperidol to reverse some of the scopolamine-induced exacerbation of verbal short-term forgetting was observed. The data indicate that scopolamine and haloperidol can independently and selectively affect cognition and that at the doses tested in this study no synergistic exacerbation of cognitive functioning was found when cholinergic blockage was coupled with dopaminergic or serotonergic blockade.
This paper reports findings from a National Institute on Drug Abuse-funded study designed to test the hypothesis that environmental changes, such as the enactment of laws to increase the accessibility of sterile syringes, including syringe exchange and pharmacy sale of syringes without a prescription, will lower the frequency of HIV risk and the prevalence of HIV among street drug users. Project COPE, a study of AIDS risk and risk prevention, collected longitudinal data on drug use, HIV risk, serostatus, and source of syringes in a sample of 710 out-of-treatment injection drug users in Hartford, CT. Findings support the hypothesis and the growing research-based conclusion that syringe exchange is an effective AIDS risk reduction modality.
A multimedia telemedicine network is proposed for a VISN-19 test bed and it will include picture archiving and communication systems (PACS). Initial tests have been performed, and the technical feasibility of the basic plan has been demonstrated.
Navy fleets have a defined overall objective for mission readiness impacted by the health of personnel aboard the ships. Medical treatment facilities on the ships determines the degree of mission readiness. This paper describes the concepts and technologies necessary to establish a Naval telemedicine system, which can drastically improve health care delivery. It consists of various combinations of the following components: Fleet Naval Medical Consultation and Diagnostic Centers, Shipboard Naval Medical Consultation and Diagnostic Centers (hospital ship or combatant ships with medical specialists on board), and Remote Medical Referring Centers such as a ship, a small Naval station annex, or a field hospital. This Naval telemedicine architecture delivers clinical medicine and continuing medical education (CME) by means of computers, video-conferencing systems, or telephony to enhance the quality of care through improved access to research, medical and nonmedical imaging, remote consultations, patient clinical data, and multimedia medical education programs. It integrates the informatics infrastructure and provides a medical telepresence among participants.
Telemedicine remote consultation and diagnosis (RCD) software is a complex and distributed system. RCD allows physicians to collaborate on radiology or pathology cases from distributed geographic locations. It is very important to simplify design, construction, and maintenance of such a system. Currently, object-oriented design methodology is used to design and develop a software system in a modular fashion. Object-oriented software is made of various objects that work together. From the design of the software system, we get information about object methods and inheritance. We also get information about which objects are contained in a particular object and which objects are used by another object. One important element that the traditional object-oriented design misses is time. We propose the use of discrete event system specification (DEVS) in the design and analysis of a software system, such as RCD. With DEVS, coupling between objects can be specified explicitly and an object behavior can be shown in time. We introduce DEVS, show the time-line analysis of Remote Consultation and Diagnosis session playback using DEVS, and then describe its implementation.
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The US health care industry is in the midst of revolutionary changes. Under tremendous pressures from third-party payers and managed care programs to control costs while providing high quality medical services, health care entities are now looking at information technologies to help them achieve their goals. These goals typically include improved productivity, efficiency and decision-making capabilities among staff members. Moreover, hospitals and other health care facilities that provide a broad and integrated range of inpatient and outpatient care, wellness and home care services are in the best position to offer comprehensive packages to managed care and private insurers. Many health care providers and administrators are considered mobile employees. This mobility can range from intra-building and intra-campus to multi-site and metropolitan areas. This group often relies on a variety of information technologies such as personal computers, communicating laptops, pagers, cellular phones, wireline phones, cordless phones and fax machines to stay in touch and handle information needs. These health care professionals require mobile information access and messaging tools to improve communications, control accessibility and enhance decision-making capabilities. AirBoss mobile messaging services could address the health care industry's need for improved messaging capabilities for its mobile employees. The AirBoss family of services supports integrated voice services, data messaging, mobile facsimile and customized information delivery. This paper describes overview of the current mobile data networking capability, the AirBoss architecture, the health care-related applications it addresses and long-term benefits. In addition, a prototype application for mobile home health care workers is illustrated. This prototype application provides integrated e-mail, information services, web access, real-time access and update of patient records from wireline or wireless networks, and cross media delivery and notification. It provides seamless wide area access to patient data in a secure environment, thus providing a continuity of care from the hospital to home.
We report the long-term results of abdominal aortic stenting in 24 patients who underwent stenting for atherosclerotic occlusive disease (16 stenoses, 6 occlusions, and 2 ulcerative plaques). The occlusions were treated initially with thrombolytic therapy, and all lesions were balloon dilated. Indications for stenting were: residual gradient (n = 10); recoil (n = 7); dissection (n = 2); and atherosclerotic debris (n = 5). Thirty-eight Palmaz stents were implanted in the aorta, and 21 were implanted in the common iliac (n = 19) and external iliac (n = 2) arteries. Technical and clinical success was 100%. Over a mean follow-up period of 48 months (range, 1 to 67 months), 2 patients died and 2 were lost to follow-up. Two patients developed symptoms referable to the aorta (at 43 and 67 months), and each was managed successfully via an endovascular approach. There was no in-stent restenosis. Life-table analysis showed a 100% cumulative primary patency at 5 years. We conclude that stenting for abdominal aortic occlusive disease appears to offer long-term patency slightly superior to that of classical surgical intervention. Aortic stents also do not appear to be subject to restenosis. Follow-up in a larger patient cohort is needed to confirm these observations.
We report the results of stenting in 17 patients who underwent treatment for total occlusions in the subclavian arteries between July 1991 and December 1995. Fourteen of the lesions were located in the left side; 15 patients had a subclavian steal syndrome. The indications for treatment were vertebrobasilar insufficiency (n = 7); arm claudication (n = 5); vertebrobasilar insufficiency and upper-limb ischemia (n = 3); protection of a left internal mammary artery coronary bypass (n = 1); and an isolated subclavian steal syndrome (n = 1). A total of 23 stents were implanted in 17 patients; in 1 patient, 2 stents migrated during deployment, resulting in a 94% procedural success rate. One case of axillary thrombosis was successfully treated with local thrombolysis and balloon angioplasty. There were no postprocedural neurologic complications or deaths. Follow-up over a mean duration of 19.4 months (range, 4 to 56 months) revealed 1 asymptomatic restenosis at 5 months in a patient with 3 stents. Life-table analysis showed an 81% cumulative patency rate at 6 months. We conclude that stenting for occlusion of the subclavian arteries appears feasible and safe; however, further evaluation in a larger group of patients is needed to confirm these results.