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PubMedDate not supplied

Creatine kinase isoenzyme BB: a lung cancer associated marker.

We investigated the diagnostic role of creatine kinase isoenzyme BB (CK-BB) in lung cancer. CK-BB was assayed using a radioimmunological system by saturation with Mallinchrodt double antibody 125I labelled (RIA Quant-CPK-BB). Sensitivity was 97% and specificity 90% in 44 cancers (T2-T3), in 36 non-cancers (chronic bronchitis) and in 48 healthy controls. Mean serum CK-BB values for patients with chronic bronchitis (2.64 +/- 1.1 ng/ml) were virtually the same as in normal subjects. Patients with lung cancer had markedly higher serum CK-BB values (9.17 +/- 2.6 ng/ml) than either the control group (healthy subjects) or the chronic bronchitis patients (p less than 0.01). These results lead us to suggest that CK-BB serum determination might prove useful in screening pulmonary disorders. However, further studies are essential to establish: 1) the relationship between serum levels of the isoenzyme and the histology and stage of the neoplastic disease; 2) the relation between CK-BB and the aggressive potential of the neoplastic clone.

Adenocarcinoma↗
PubMed1999

[Crohn's disease: evaluation with computed tomography and magnetic resonance imaging].

Computed Tomography should increasingly be used as a minimally invasive alternative to small bowel enteroclysis. Firstly, CT-examination is less stressful to the patients. Secondly, information is not only provided about the bowel lumen but in addition the thickness and architecture of the small bowel wall as well as the adjacent structures can be evaluated. Extraintestinal lesions/complications are easily diagnosed. Moreover, CT can be used as primary screening method in the evaluation of abdominal complaints of unknown origin. Next to Crohn's disease, numerous other small bowel diseases can be excluded. Magnetic resonance imaging will become another alternative imaging technique in future. Major advantages are the lack of ionizing radiation, the multiplanar scanning technique and the possibility of extensive postprocessing by virtual endoscopy.

Adolescent↗
PubMed1964

PROGRESS IN CHEMOTHERAPY OF CANCER.

The chemotherapy of cancer, in relation to surgery and radiotherapy, is a new method of attack. Its development, which started virtually in the 1940's, was reviewed by the WHO Expert Committee on Chemotherapy of Cancer that met in September 1961. The report of the Committee dealt with experimental and clinical studies in this field critically, but also to a necessary degree, comprehensively. The design and mechanism of action of the drugs, their biological screening and subsequent clinical trials were discussed, and a review was presented of the clinically available drugs and the neoplasms for which they were indicated. In the two years that have elapsed since the report was drawn up many new compounds have been tested and some have had clinical trials. There have been developments, too, in methods of administration. All these new developments are discussed in the present paper.

Alkaloids↗
PubMed1993

Round and round it goes: the epidemiology of childhood lead poisoning, 1950-1990.

In the 40 years from 1950 to 1990, lead epidemiology and public policy based on it made enormous strides. Exposure levels that caused concern in the medical and public health community fell from 80 to 10 micrograms/dL of blood. In the space of 20 years, beginning in 1970, first the surgeon general and then the CDC lowered the official "level of concern" from 50 or 60 to 10 micrograms/dL. The public health community has turned its attention from the prevention of poisoning that results in encephalopathy, mental retardation, and death to the reduction of exposure to avoid subtle neurobehavioral deficits that are detectable only in fairly large epidemiological studies. Numerous advances in technology and analysis have facilitated progress in lead epidemiology. In order to show that intellectual deficits were related to lead exposure rather than to such confounding variables as parental education, parental IQ, income, or parents' age at time of birth, researchers performed extensive regression analyses of fairly large sample populations, controlling for as many as 39 confounding variables. These analyses would have been virtually impossible but for the development of computer software programs that became available beginning in the late 1960s and early 1970s. Handling of large data bases, such as NHANES II, also required access to computer hardware and software not generally available earlier. The existence of the data depended on other technological innovations that made screening of large populations inexpensive and relatively simple. In 1973, erythrocyte protoporphyrin screening transformed testing for lead poisoning. With the advent of atomic absorption spectroscopy and rapid improvement in equipment for blood lead analysis, obtaining blood lead levels became less expensive and easier and produced more accurate results. Increasing attention both to preventing environmental contamination of samples and to controlling laboratory quality also improved the accuracy of data collected. Advances in screening and analytical technology made the mass screening of the 1970s possible--both the programs coordinated by the CDC and NHANES II. NHANES II showed the extent of the problem of lead exposure to be even greater than previously thought. It was estimated that in 1980 almost 2 percent of all children aged six months to five years had blood lead levels over the CDC level of concern of 30 micrograms/dL. More than 13 percent of black children had levels above 30 micrograms/dL. Lead was certainly the most widespread threat to child health in America. In 1985, when the CDC lowered the level of concern to 25 micrograms/dL, the population defined to be at risk tripled.(ABSTRACT TRUNCATED AT 400 WORDS)

Attitude to Health↗
PubMed1994

nmt2 of fission yeast: a second thiamine-repressible gene co-ordinately regulated with nmt1.

We previously described a screen for thiamine-repressible genes in Schizosaccharomyces pombe and reported on one such gene, nmt1, required for thiamine biosynthesis. Here we describe a second gene, nmt2, recovered in the same screen. Disruption of nmt2 also resulted in thiamine auxotrophy, indicating a role for the nmt2 gene product in thiamine biosynthesis. Both genes are highly transcribed in minimal medium and repressed in medium containing thiamine, and nuclear 'run-on' experiments confirm that expression in both cases is controlled by the rate of transcription initiation. The virtually identical kinetics of induction and repression suggest that the two genes are co-ordinately regulated. Sequence comparison of the two promoters reveals a canonical TATA box, downstream of which is a perfectly conserved 11 bp element. Transcript mapping experiments show that transcription initiation of both genes is centred on this element.

Amino Acid Sequence↗
PubMed2006

[The foundations of computer assisted surgery].

Using navigation systems in general orthopaedic surgery and, in particular, knee replacement is becoming more and more accepted. This paper describes the basic technological concepts of modern computer assisted surgical systems. It explains the variation in currently available systems and outlines research activities that will potentially influence future products. In general, each navigation system is defined by three components: (1) the therapeutic object is the anatomical structure that is operated on using the navigation system, (2) the virtual object represents an image of the therapeutic object, with radiological images or computer generated models potentially being used, and (3) last but not least, the navigator acquires the spatial position and orientation of instruments and anatomy thus providing the necessary data to replay surgical action in real-time on the navigation system's screen.

Computer Graphics↗
PubMedDate not supplied

Changes in antimicrobial agent usage resulting from interactions among clinical pharmacy, the infectious disease division, and the microbiology laboratory.

Rapid reporting of culture and susceptibility data is the first of several important steps in the successful management of infected patients. As has been said many times, rapidly reported data are of little value unless the patient directly benefits. Benefit requires better overall communication and an action plan linked to timely use of these results. In 1989 the Millard Fillmore Hospital Antibiotic Review Committee developed and implemented a prototype approach to hospital wide antimicrobial management. The formulary was revised and the drug use evaluation process modified to enhance effectiveness and to lower the cost of therapy and inventory. Clinical pharmacy antimicrobial agent management specialists were then recruited to individualize patient treatments to the isolated pathogens in conjunction with the Division of Infectious Diseases. To provide the clinical pharmacy specialists with rapid and clinically useful information, a real-time computer link was created between the pharmacy (antibiotic orders) and the microbiology laboratory (culture results). Customized software was implemented to screen all patients automatically for mismatches between pathogens and drugs, or to screen for doses inappropriate to minimum inhibitory concentration or renal function. Special attention was paid to identification of opportunities to target a more appropriate narrow-spectrum regimen after culture results became available. Changes in antimicrobial regimen or dosage were made by contacting the prescribing physician. Over 90% of the recommended changes were made, and virtually all changed regimens had satisfactory clinical outcome. Real dollar expenditures for antimicrobial agents declined by > $200,000 per year. Prior to the institution of this computerized clinical management strategy, antimicrobial purchases were rising yearly at the rate of 12%-15%. The combined efforts of clinical pharmacy, microbiology, and infectious disease personnel successfully optimized antimicrobial therapy on a hospital wide basis. Antimicrobial agent optimization improved patient outcome, and the cost savings more than covered the costs of the program personnel and software.

Anti-Bacterial Agents↗
PubMed1997

Discrete representations of the protein C alpha chain.

BACKGROUND: When a large number of protein conformations are generated and screened, as in protein structure prediction studies, it is often advantageous to change the conformation in units of four consecutive residues at a time. The internal geometry of a chain of four consecutive C alpha atoms is completely described by means of the three angles theta 1, tau, and theta 2, where tau is the virtual torsion angle defined by the four atoms and theta 1 and theta 2 are the virtual bond angles flanking the torsion angle on either side. In this paper, we examine the quality of the protein structures that can be obtained when they are represented by means of a set of discrete values for these angles (discrete states). RESULTS: Different models were produced by selecting various different discrete states. The performance of these models was tested by rebuilding the C alpha chains of 139 high-resolution nonhomologous protein structures using the build-up procedure of Park and Levitt. We find that the discrete state models introduce distortions at three levels, which can be measured by means of the 'context-free', 'in-context', and the overall root-mean-square deviation of the C alpha coordinates (crms), respectively, and we find that these different levels of distortions are interrelated. As found by Park and Levitt, the overall crms decreases smoothly for most models with the complexity of the model. However, the decrease is significantly faster with our models than observed by Park and Levitt with their models. We also find that it is possible to choose models that perform considerably worse than expected from this smooth dependence on complexity. CONCLUSIONS: Of our models, the most suitable for use in initial protein folding studies appears to be model S8, in which the effective number of states available for a given residue quartet is 6.5. This model builds helices, beta-strands, and coil/loop structures with approximately equal quality and gives the overall crms value of 1.9 A on average with relatively little variation among the different proteins tried.

Models, Chemical↗
PubMed1990

Elimination of z-ejection in Fourier transform ion cyclotron resonance mass spectrometry by radio frequency electric field shimming.

In Fourier transform ion cyclotron resonance (FT/ICR) mass spectrometry, coherent ion cyclotron orbital motion is produced by resonant radio frequency (rf) electric field excitation. However, because the excitation electrodes are of finite dimensions, the desired transverse (to the applied magnetic field) rf electric field is accompanied by an rf electric field component along the z- (magnetic field) direction, resulting in mass-dependent z-ejection and mass-dependent FT/ICR mass spectral peak relative magnitudes. Addition of several "guard wires" of voltage-divided rf amplitude allows the rf electric field to be "shimmed" to near-perfect uniformity. In this paper (see also the accompanying paper by Russell et al.), we introduce two types of rf-shimmed ion traps. In the first type, guard wires are placed only in front of the trapping electrodes. In the second type, guard wire rings are placed inside the detector and trapping electrodes. For either arrangement, simion simulations were used to adjust the rf voltages applied (by use of voltage dividers) to the guard wires or rings so as to produce an optimally uniform rf field within the trap. The virtual elimination of z-excitation is confirmed by plots of magnitude-mode relative peak height vs ICR orbital radius. Because the guard wires (or rings) tend to shield the ions from the trapping electrode potential, the shift in ICR frequency with trapping voltage is also reduced, but not as well as by a screened trap.(ABSTRACT TRUNCATED AT 250 WORDS)

Fourier Analysis↗
PubMed2006

Functional characterization of IRESes by an inhibitor of the RNA helicase eIF4A.

RNA helicases are molecular motors that are involved in virtually all aspects of RNA metabolism. Eukaryotic initiation factor (eIF) 4A is the prototypical member of the DEAD-box family of RNA helicases. It is thought to use energy from ATP hydrolysis to unwind mRNA structure and, in conjunction with other translation factors, it prepares mRNA templates for ribosome recruitment during translation initiation. In screening marine extracts for new eukaryotic translation initiation inhibitors, we identified the natural product hippuristanol. We show here that this compound is a selective and potent inhibitor of eIF4A RNA-binding activity that can be used to distinguish between eIF4A-dependent and -independent modes of translation initiation in vitro and in vivo. We also show that poliovirus replication is delayed when infected cells are exposed to hippuristanol. Our study demonstrates the feasibility of selectively targeting members of the DEAD-box helicase family with small-molecule inhibitors.

Adenosine Triphosphate↗
PubMed2000

[Use of virtual endoscopy with computerized tomography in the identification of colorectal neoplasms. Prospective study with symptomatic patients].

INTRODUCTION: Aim of this study was to evaluate the sensitivity of virtual colonoscopy (CT colonography) in the identification of colorectal cancer and to define the limitations and the advantages of this imaging modality, as well as indications to the examination. MATERIAL AND METHODS: We examined prospectively 62 symptomatic patients aged 36 to 82 years (28 women and 34 men). All patients underwent both conventional and virtual colonoscopy on the same day; the conventional examination allowed exploration of the entire colon. RESULTS: Conventional colonoscopy identified 89 lesions 3-50 mm in diameter, namely 84 benign and 5 malignant lesions. No lesions were identified in 12 patients. CT colonography identified 52 of the 89 lesions, with 57.1% diagnostic accuracy. There were 11 false positives (82.5% positive predictive value and 52.2% specificity) and 37 false negatives (24.5% negative predictive value and 58.4% sensitivity). Sensitivity was significantly higher (85.7%) for polyps > or = 1 cm. CONCLUSIONS: Virtual colonoscopy is an imaging modality with good diagnostic yield, well tolerated by patients and with great potentials for further development. We suggest that the examination be performed in symptomatic patients who cannot undergo total colonoscopy or refuse the other imaging modalities. Further studies are warranted in larger series of patients, possibly introducing it in screening programs.

Adult↗
PubMed2001

Development of an experimental paradigm in which to examine human learning using two computer-based formats.

Computer-based self-instructional programs are frequently promoted as means to augment or replace the traditional anatomy curricula taught in medical schools. These programs may range from static slide shows to fully immersive virtual environments. However, the impact of these learning technologies on knowledge acquisition, and their comparative cost/benefit to education remain unclear. As a consequence, we are embarking on a series of experiments to compare knowledge acquisition and the meaningful use of information among students who are learning anatomy using one of two different computer-based self-instructional formats. These studies will be based on a specially developed learning module on basic lung anatomy; they will utilize a variety of assessment tools to measure factual knowledge, conceptual understanding of spatial-anatomic relationships, and the ability to apply newly acquired knowledge of anatomy to clinical problem-solving scenarios. The primary object of this paper is to describe the design and development of the underlying test module and to outline the two computer-based formats that will be evaluated. The virtual reality (VR) environment, UCSD's Anatomic VisualizeR, provides dynamic access to 3-dimensional polygonal models of the lesson content and supports student-centered exploration and learning. The multimedia environment, Microsoft PowerPoint, provides a structured presentation of the lesson content and illustrates important anatomic structures through the use of 2-dimensional images derived by screen captures of models available in the VR learning module. This paper also provides an overview of the first experiment in the series, a pilot study using first-year medical students without previous participation in a medical school anatomy curriculum. For this study, students will be prospectively randomized into two groups, each group learning the lung anatomy lesson using one of the computer-based formats described. Immediate knowledge retention will be measured by asking students to complete the assessment instrument immediately after completing their learning module. The results of the pilot study will be used to refine and improve the design of the remainder of studies planned in this experimental series.

Anatomy↗
PubMed1995

New nucleoside analogues for chronic hepatitis B.

In recent years, an in vitro system for screening nucleoside analogues against hepatitis B virus has yielded several compounds with a high therapeutic index. Phase I and II studies have also shown a potent in vivo antiviral effect of fialuridine and lamivudine in patients with chronic hepatitis B. The use of fialuridine was associated with unexpectedly severe mitochondrial dysfunction; in contrast, lamivudine had virtually no side-effects. Experience in liver transplant patients with recurrent hepatitis B shows that famciclovir may be another effective antivirotic drug with good tolerance.

2-Aminopurine↗
PubMed2005

Combinatorial chemistry and fragment screening--two unlike siblings?

Efficiently scouting the chemical space is one of the major challenges for lead discovery for drug development. In recent times some shifts have been made away from HTS and combinatorial chemistry to more focused approaches. Combinatorial chemistry was the starting point for the development of synthesis concepts that were intended to cover and explore the chemical space without having to prepare every individual compound. In this review, these lead finding approaches will be discussed comparing virtual and synthesized libraries. In addition we discuss the concepts and relationships of evolutionary libraries using genetic algorithms and dynamic combinatorial chemistries, as well as templated fragment ligation concepts. Taking a more abstract view of all approaches, the concepts may loop back into Combinatorial Chemistry allowing a more educated choice of building blocks and chemistries.

Combinatorial Chemistry Techniques↗
PubMedDate not supplied

Intracavernous injection during diagnostic screening for erectile dysfunction; five-year experience with over 600 patients.

Psychophysiological diagnostic screening (PDS) was carried out on just over 1000 consecutive patients with erectile dysfunction (ED) during 1995 through 1999. Roughly one-third did not require an intracavernous injection (ICI) because of optimal penile response during visual and tactile penile sexual stimulation. The present article deals with those other patients (n = 609) who required an ICI and completed a 24-hour-postinvestigation questionnaire (PIQ). The two ICI preparations used, prostaglandin and papaverine + fentolamine, were virtually equally effective in the doses applied, with very low and similar percentages of unwanted side effects, for example, prolonged erection. Somatic ED patients displayed the lowest penile responses to ICI, whereas psychogenic ED patients had the highest penile responses. ED patients who also suffered from premature ejaculation (PE) ejaculated significantly more readily during PDS that those without PE. An ICI following an ejaculation/orgasm could lead to an erection presumably sufficient for intromission, which indicates ICI as a therapeutic option for rapid ejaculators. Our elaborate and lengthy PDS procedure, particularly the use of penile vibration as an addition to the visual sexual stimulation, obviates the diagnostic use of the PIQ.

Adjuvants, Immunologic↗
PubMed2006

Single-assay combination of Epstein-Barr Virus (EBV) EBNA1- and viral capsid antigen-p18-derived synthetic peptides for measuring anti-EBV immunoglobulin G (IgG) and IgA antibody levels in sera from nasopharyngeal carcinoma patients: options for field screening.

Assessment of immunoglobulin A (IgA) antibody responses to various Epstein-Barr virus (EBV) antigen complexes, usually involving multiple serological assays, is important for the early diagnosis of nasopharyngeal carcinoma (NPC). Through combination of two synthetic peptides representing immunodominant epitopes of EBNA1 and viral capsid antigen (VCA)-p18 we developed a one-step sandwich enzyme-linked immunosorbent assay (ELISA) for the specific detection of EBV reactive IgG and IgA antibodies in NPC patients (EBV IgG/IgA ELISA). Sera were obtained from healthy donors (n = 367), non-NPC head and neck cancer patients (n = 43), and biopsy-proven NPC patients (n = 296) of Indonesian and Chinese origin. Higher values of optical density at 450 nm for EBV IgG were observed in NPC patients compared to the healthy EBV carriers, but the large overlap limits its use for NPC diagnosis. Using either EBNA1 or VCA-p18 peptides alone IgA ELISA correctly identified 88.5% and 79.8% of Indonesian NPC patients, with specificities of 80.1% and 70.9%, whereas combined single-well coating with both peptides yielded sensitivity and specificity values of 90.1 and 85.4%, respectively. The positive and negative predictive values (PPV and NPV, respectively) for the combined EBNA1 plus VCA EBV IgA ELISA were 78.7% and 93.9%, respectively. In the Indonesia panel, the level of EBV IgA reactivity was not associated with NPC tumor size, lymph node involvement, and metastasis stage, sex, and age group. In the China panel the sensitivity/specificity values were 86.2/92.0% (EBNA1 IgA) and 84.1/90.3% (VCA-p18 IgA) for single-peptide assays and 95.1/90.6% for the combined VCA plus EBNA1 IgA ELISA, with a PPV and an NPV for the combined EBV IgA ELISA of 95.6 and 89.3%, respectively. Virtually all NPC patients had abnormal anti-EBV IgG diversity patterns as determined by immunoblot analysis. On the other hand, healthy EBV carriers with positive EBV IgA ELISA result showed normal IgG diversity patterns. By using EBV IgG immunoblot diversity as confirmation assay for EBV IgA ELISA-positive samples, the sensitivity and specificity for NPC diagnosis increased to 98% and 99.2%, respectively, in the Indonesian NPC samples. The use of these combined methods for seroepidemiological screening studies is proposed.

Antigens, Viral↗
PubMed2003

Male sexual dysfunctions and multimedia immersion therapy (follow-up).

The aim of the study was to evaluate the efficiency, after 1 year, of combined use of psychodynamic psychotherapy integrating virtual reality (VR) for the treatment of erectile dysfunction (ED) and premature ejaculation (PE) in 160 heterosexual males who had neither any prior sexual therapy nor had made use (either before, during or after therapy) of any specific pharmaceuticals for the treatment of primary sexual dysfunction. All subjects had given their informed consent. After a clinical diagnosis in an andrologic center, 50 presumably psychological ED (average age 43.7 years), 60 mixed ED (53.9 years) and 50 primary PE (39 years) who suffered these problems over 6 months were undergoing a cycle of 12 sessions, over a 25-week period, of psychotherapy, integrating an audio CD and helmet with miniature television screens that projected specially designed CD-ROM program on the ontogenetic development of male sexual identity. The clinical follow up was done after 6 and 12 months after the cycle. After one year, the overall partial (two times out of three) and complete positive response rate for psychological ED was 75%, for mixed ED was 47% and for PE was 54%. We considered drop-out cases as only before the 7th session of the treatment cycle, the drop-outs after session 7 and the patients that did not show up for follow-up are counted as negative results. Two patients reported nausea and one, vertigo during the first 15-min virtual reality experience. Considering the particular way that full-immersion virtual reality involves the subject who experiences it, we hypothesized that this methodological approach could speed up the therapeutic process. The evidence that positive results persist over time allows us to hypothesize that certain changes in cerebral function can be possible and that these changes are correlated to favorable sexual performance in the male.

Adult↗
PubMed1988

Incidence of ras gene mutations in neuroblastoma.

Using a rapid dot-blot screening procedure based on DNA amplification and hybridization to synthetic oligonucleotide probes, we investigated 18 neuroblastomas in various clinical stages for the presence of ras mutations. In none of the samples was a mutation in the relevant codons 12, 13 or 61 of Ha-ras, Ki-ras or N-ras found. These data virtually exclude the participation of mutated ras genes in the genesis of neuroblastoma.

DNA Mutational Analysis↗