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Virtual reality in surgery and medicine.

This report documents the state of development of enhanced and virtual reality-based systems in medicine. Virtual reality systems seek to simulate a surgical procedure in a computer-generated world in order to improve training. Enhanced reality systems seek to augment or enhance reality by providing improved imaging alternatives for specific patient data. Virtual reality represents a paradigm shift in the way we teach and evaluate the skills of medical personnel. Driving the development of virtual reality-based simulators is laparoscopic abdominal surgery, where there is a perceived need for better training techniques; within a year, systems will be fielded for second-year residency students. Further refinements over perhaps the next five years should allow surgeons to evaluate and practice new techniques in a simulator before using them on patients. Technical developments are rapidly improving the realism of these machines to an amazing degree, as well as bringing the price down to affordable levels. In the next five years, many new anatomical models, procedures, and skills are likely to become available on simulators. Enhanced reality systems are generally being developed to improve visualization of specific patient data. Three-dimensional (3-D) stereovision systems for endoscopic applications, head-mounted displays, and stereotactic image navigation systems are being fielded now, with neurosurgery and laparoscopic surgery being major driving influences. Over perhaps the next five years, enhanced and virtual reality systems are likely to merge. This will permit patient-specific images to be used on virtual reality simulators or computer-generated landscapes to be input into surgical visualization instruments. Percolating all around these activities are developments in robotics and telesurgery. An advanced information infrastructure eventually will permit remote physicians to share video, audio, medical records, and imaging data with local physicians in real time. Surgical robots are likely to be deployed for specific tasks in the operating room (OR) and to support telesurgery applications. Technical developments in robotics and motion control are key components of many virtual reality systems. Since almost all of the virtual reality and enhanced reality systems will be digitally based, they are also capable of being put "on-line" for tele-training, consulting, and even surgery. Advancements in virtual and enhanced reality systems will be driven in part by consumer applications of this technology. Many of the companies that will supply systems for medical applications are also working on commercial products. A big consumer hit can benefit the entire industry by increasing volumes and bringing down costs.(ABSTRACT TRUNCATED AT 400 WORDS)

Computer Simulation↗

2001 salary survey.

Boards are coming to respect how challenging it is to run a hospital, and increasingly view it as too big a job for one person. In our annual compensation survey report, Hay Group analysts assert that lower-level executives, senior managers and even middle managers have seen their stock rise in health care organizations, and that's reflected in the pay structure. Even so, CEOs aren't exactly struggling--but their total compensation still lags behind that of their counterparts in other industries.

Chief Executive Officers, Hospital↗

Disulfide bonds in native and recombinant fish growth hormones.

Disulfide linkages were characterized for the first time in a fish growth hormone. Trypsin digestion of chum salmon growth hormone, followed by mass spectrometry established that Cys-49 is linked to Cys-161, while Cys-178 is linked to Cys-186. This is analogous to the big loop, little loop pattern found in human growth hormone. Ninety-three percent of the primary structure of a recombinant rainbow trout growth hormone whose cDNA codes for the same amino acid sequence as chum salmon growth hormone was confirmed by mass spectrometric peptide mapping.

Amino Acid Sequence↗

[History of the Red Army pathoanatomical service in World War II 1941-1945].

History of the rise of the pathology service in the system of the military-medical service of the Red Army is described and the arguments in favour of its necessity in the fighting troops are presented. The characterization of the goals of such a service is given, notably: an evaluation of the work of the military-medical establishments on the basis of a summarized clinico-anatomical analysis of pathology data, this allowing the heads of the military-medical service a rapid elimination of organizational and therapeutic-diagnostic defects of various stages of medical evacuation and improvement of the activity of the therapeutic evacuation centres; establishing the causes of death of the persons wounded or struck in the battles and evaluating the significance of the type, time, volume and shortcomings of the treatment in the fatal issue; studying the pathology of the war trauma, regeneration, the pathogenesis of infectious complications and influence on their development and course of the treatment, etc. The organizational structure of the service, its branches (front and army laboratories of pathology, department of pathology of big hospitals) working under the guidance of the Central Laboratory of Pathology (CLP), is described. The documents which were the basis of the work of these laboratories are characterized. An important merit of M.F. Glazunov and N. A. Krayevsky--chiefs of the CLP--in the organization and guidance, both practical and scientific, is noted. The main results of the activity of the service are briefly characterized.

History, 20th Century↗

An experimental study of tumour size and radiosensitivity: analysis by regrowth delay.

When designing experimental studies of tumours, it is considered important to control all variables that might alter the radiosensitivity and hence influence the variability of the data. One such variable is tumour size. We have studied the regrowth delay of a mammary carcinoma treated at 2-10 mm mean diameter (a 125-fold change of volume) with X-rays alone or X-rays plus misonidazole (MISO). The data were analysed to give dose-response curves, using four endpoints. Regrowth to a fixed size (4.5 mm larger than treatment size), or by a fixed increment (4 times the original volume) was expressed either as absolute delay, or as specific growth delay to allow for the changes in volume doubling time as the tumour grows. The method of analysis made no difference to the measured sensitizer enhancement ratio (SER) for MISO. The SER was dose-dependent, being higher at higher doses, but was not different in tumours of 2 or 10 mm diameter. However, when comparing response to X-rays alone, the method of analysis made a very big difference to the conclusions. Regrowth to R + 4.5 mm showed no change in radiosensitivity with tumour size, but regrowth to 4 times the original volume (the most logical endpoint) indicated that large tumours were more sensitive than small. We conclude that regrowth delay may be an inappropriate method for comparing absolute sensitivities of tumours of different sizes. However, for studying the effectiveness of a radiomodifier the constraints of tumour size at irradiation seem to be less severe than previously believed.

Animals↗

The Big Blue(R) transgenic mouse mutation detection assay: the mutation pattern of sectored mutant plaques.

There are mutational artifacts in the Big Blue(R) assay and it is important to characterize the source and nature of these mutations. Differences were reported in the mutation patterns of a small sample of 23 sectored and 91 circular mutant plaques derived from skin using the Big Blue(R) transgenic mouse mutation detection system [G. R. Stuart, N.J. Gorelick, J.L. Andrews, J.G. de Boer, B.W. Glickman, The genetic analysis of lacI mutations in sectored plaques from Big Blue transgenic mice, Environ. Mol. Mutagen 28 (1996) 385-392.]. We have extended these observations by analyzing 46 sectored and 224 circular mutant plaques derived from seven tissues. The frequency of sectored mutant plaques is estimated to be 16% with no significant variation with tissue type. However, the patterns of mutation for sectored mutants and mouse-derived mutations differed significantly (p=0.04). Base substitutions in sectored mutant plaques do not show the asymmetries found in circular mutants consistent with integration of a GC rich transgene into the AT rich mammalian genome. Sectored mutants have mutation patterns consistent with a mixture of mouse, in vitro and Escherichia coli-derived mutations. Data on the relative frequencies of different mutant plaque morphologies suggests that overlapped plaques are substantially contaminated by sectored plaques at recommended plating densities.

Animals↗

Mutation frequency and specificity with age in liver, bladder and brain of lacI transgenic mice.

Mutation frequency and specificity were determined as a function of age in nuclear DNA from liver, bladder, and brain of Big Blue lacI transgenic mice aged 1.5-25 months. Mutations accumulated with age in liver and accumulated more rapidly in bladder. In the brain a small initial increase in mutation frequency was observed in young animals; however, no further increase was observed in adult mice. To investigate the origin of mutations, the mutational spectra for each tissue and age were determined. DNA sequence analysis of mutant lacI transgenes revealed no significant changes in mutational specificity in any tissue at any age. The spectra of mutations found in aging animals were identical to those in younger animals, suggesting that they originated from a common set of DNA lesions manifested during DNA replication. The data also indicated that there were no significant age-related mutational changes due to oxidative damage, or errors resulting from either changes in the fidelity of DNA polymerase or the efficiency of DNA repair. Hence, no evidence was found to support hypotheses that predict that oxidative damage or accumulation of errors in nuclear DNA contributes significantly to the aging process, at least in these three somatic tissues.

Aging↗

Drinking in France 1965-1979. An analysis of household consumption data.

Alcohol consumption has diminished in France for three decades. In this France is an exception to other industrialized countries. However, in one respect France conforms to a regularity found in longitudinal time-series studies comparing different countries: traditional beverages, in this case wine, have given place to new drinks--beer and imported spirits. In this sense, drinking patterns have become modernized and now resemble those found in other Western industrialized countries. The article, based on a series of household consumption surveys that include purchases of alcoholic beverages by households, studies in what way this modernization is taking place. A break-down of the data by socio-demographic groups shows that saturation as such does not explain the change. The groups that already have been at the lowest level of consumption--the middle classes--have diminished their consumption further and the other groups--the peasantry and the working class--have followed them. The same is true as regards drinking styles, as much as they are revealed by the beverage types. The already modern middle classes have continued to decrease their consumption of wine and the other groups have done likewise but later. In contrast, the rural-urban dimension is and has been weakly related to alcohol use. The development has been parallel both in big cities and rural areas. The analysis by region reveals that in France the use of alcohol and especially wine is no longer related to alcohol production, the way it is in international comparisons--producing countries being also the heaviest consumers. On the other hand, consumption patterns, as reflected in the beverage composition, have not levelled out between regions. One conclusion of the study is that the culturally dominating social dimension in France is that of class. In so far as the lower social groups continue to follow the dominating ones, the development can be expected to continue still for a long time.

Alcohol Drinking↗

[Personality and personality disorders I. Universality and sensitivity of dimensional personality models as diagnostic systems for personality disorders].

OBJECTIVE: A dimensional diagnostic system for personality disorders (PD) postulates continuous transitions from normal to disordered personalities (continuity hypothesis) and universal validity of basic personality dimensions (universal hypothesis). In the present study three dimensional personality models that claim to provide a systematic representation of the overall domain of personality disorders were compared: the Big-Five model proposed by Costa and McCrae, the psychobiological model proposed by Cloninger and colleagues, and the "Dimensional Assessment of Personal Pathology (DAPP)" model proposed by Livesley and colleagues. METHOD: The "Six Factor Test" (SFT) measuring the Big-Five factors of personality, the "Temperament and Character Inventory (TCI)" measuring 4 temperament and 3 character dimensions, and the DAPP measuring 18 basic traits and 4 second ordered factors were administered to general population subjects (n = 156), and a clinical sample (n = 220) including a subsample of 69 patients with at least one diagnosis of DSM-IV PD. Group comparisons, regression analyses, and facet theoretical analyses were conducted. RESULTS: The nonmetric similarity analyses of the three personality models show a nearly identical radex-representation of the second ordered factors in the non-clinical and clinical sample reflecting an universal validity of 4 basic personality dimensions and confirming the universal hypothesis. In comparison with the BIG-Five concept and the psychobiological model the DAPP model seems to be more sensitive to differentiate PD patients from controls with a reclassification rate of 94.5 %. CONCLUSIONS: The Big-Five model, the DAPP and the TCI represent a substantially similar domain despite their different conceptualization. However, the DAPP was more sensitive to differences between PD patients and controls, offered a more comprehensive account of PD, and could differentiate the two groups more effectively.

Character↗

cDNA cloning and sequence analysis of preproendothelin-1 (PPET-1) from salmon, Oncorhynchus keta.

The presence of endothelin (ET)-like immunoreactivity and the cardiovascular effects of mammalian ET-1 in fish have been reported. To identify ET-related peptides in fish, we screened the cDNA library of the salmon (Oncorhynchus keta) stomach by means of rapid amplification of cDNA ends, and we cloned cDNAs encoding an ET-related peptide. The salmon ET-related sequence of 21 amino acids is identical to the trout ET-1 peptide recently purified from kidney specimens of Oncorhynchus mykiss. The deduced amino acid sequence of salmon pre-proET-1 (PPET-1) comprises 244 amino acids, including a putative signal sequence and mature ET-1, as well as big ET-1 and ET-1-like sequences. This precursor, the first reported PPET-1 sequence for Salmoniformes, Teleostei, has low homology with the sequences of human, mouse, frog (Xenopus laevis), and zebrafish (Danio rerio) PPET-1 (26%, 29%, 24%, and 39%, respectively).

Amino Acid Sequence↗

Assessment of atmospheric mercury emissions in Finland

This paper is part of the study of atmospheric emissions of heavy metals conducted by the Finnish Environment Institute in collaboration with the Technical Research Centre of Finland (VTT) under the umbrella of the Finnish Ministry of the Environment. The scope of our study is limited solely to anthropogenic mercury that is emitted directly to the atmosphere. This article addresses emission factors and trends of atmospheric mercury emissions during the 1990s and is based mainly on the database of the Finnish Environmental Administration. In addition, data based on the measurements taken by the VTT regarding emission factors have been used to estimate emissions of mercury from the incineration of waste. The study indicates that the total emission of mercury has decreased from 1140 kg in 1990 to 620 kg in 1997, while industrial and energy production have been on the increase simultaneously. The 45% emission reduction is due to improved gas cleaning equipment, process changes, automation, the installation of flue gas desulfurization process in coal-fired power plants and strict pollution control laws. In the past, some authors have estimated a higher mercury emission in Finland. In this study, it is also observed that there are no big changes in the quality of raw materials. Estimated emission factors can be of great help to management for estimating mercury emissions and also its risk assessment.

Journal Article↗

[Subacute sclerosing panencephalitis (SSPE) in Poland in the years 1993-1995. The sixth stage of epidemiological research].

Data was collected about 49 newly diagnosed cases of SSPE in the years 1993-1995 in Poland. In the analyzed period of time a falling of tendency the incidence of SSPE was maintained. Overall incidence--0.42 per million population, was lower than the incidence in years 1990-1992, when it was 0.72. The tendency of a shift towards older age group was maintained--the peak incidence was observed among 19 year olds, as opposed to 15 year olds in the previous analyzed time period. The authors explain the dropping SSPE incidence in Poland with a drop in measales incidence, which is a consequence of growing measles vaccine coverage rates. The influence of a big measles epidemic which occurred in 1989-1990 on a potential rise in number of SSPE cases has not been noted, but further observations are needed.

Adolescent↗

p53 wild-type and p53 nullizygous Big Blue transgenic mice have similar frequencies and patterns of observed mutation in liver, spleen and brain.

Transgenic mouse mutation detection systems offer a powerful tool for analysis of spontaneous and induced mutations in vivo. Mice doubly transgenic for a null mutation of the p53 tumor suppressor gene and a lambda shuttle vector harboring the lacI gene were utilized to examine the rate and pattern of spontaneous somatic mutation of the lacI transgene in vivo. Three somatic tissues were examined: liver, spleen and brain. At 6 weeks of age, three p53 wild type (+/+) and three p53 nullizygous (-/-), lacI (+/-) male mice were analysed. The mutation frequencies in the two genotypes were similar. The mutant frequencies for wild type (+/+) and nullizygous (-/-) p53 genotypes were, respectively, 4.2 x 10(-5) and 3.6 x 10(-5) in the liver, 4.3 x 10(-5) and 3.4 x 10(-5) in the spleen and 2.8 x 10(-5-) and 3.0 x 10(-5) in the brain. When the data from the three tissues were combined, the mutant frequency was 3.7 x 10(-5) for the (+/+) genotype and 3.3 x 10(-5) for the (-/-) genotype. By sequencing both strands in the DNA-binding region of the lacI gene, 91 mutations were found. When recurrent mutations in the same mouse were excluded, a total of 67 definitely independent mutations were found. No statistically significant differences were found in the mutational spectra between the two genotypes when the three tissues were analysed individually or combined (P = 0.58). These findings suggest a need to reconsider the general form of hypothesis that the p53 gene serves as the 'guardian of the genome'.

Animals↗

Effects of polyhalogenated aromatic hydrocarbons and related contaminants on common tern reproduction: integration of biological, biochemical, and chemical data.

In eight Dutch or Belgian common tern (Sterna hirundo) colonies, breeding biology and food choice were determined, and 15 second eggs were collected from three-egg clutches for artificial incubation, biochemical analysis and analysis of yolk-sac polyhalogenated hydrocarbon (PHAH) levels. Results from these analyses were combined with biological data from the eggs remaining in each clutch. In some breeding colonies severe flooding, rainy and cold weather, and extreme predation caused extensive losses of eggs and chicks. A relationship was found between yolksac mono-ortho polychlorinated biphenyl (mo-PCB) levels and main food species (fish or insects) of the adult terns before egg-laying. Colony average breeding data differed only slightly, and were difficult to relate to PHAH-levels. When the colonies were grouped after yolksac PHAH-patterns and main food species, significant differences in average egg laying date, incubation period, egg volume and chick weight could be related to differences in yolksac PHAH and retinoid levels, and hepatic ethoxyresorufin-O-deethylase (EROD) activity. The data from all colonies also were combined into one data-set and correlated with the biochemical parameters and PHAH levels. In summary higher yolksac PHAH levels or hepatic EROD-activity correlated with and later egg laying, prolonged incubation period and smaller eggs and chicks. Lower yolksac retinoid- and plasma thyroid hormone levels, and a higher ratio of plasma retinol over yolksac retinoids correlated with later egg laying, prolonged incubation periods and smaller chicks and eggs. The dynamic environment of the terns had more obvious detrimental effects on breeding success than PHAHs. However, the more subtle effects observed for PHAHs could still be of importance during specific stress circumstances. To monitor site-specific reproduction effects, tree-nesting birds feeding on relatively big and non-migrating fishes would be most suitable. The use of specific biomarkers for exposure and effect is recommended to establish a causal relationship between a certain class of pollutants and an adverse biological effect.

Animals↗

Human endothelin-converting enzyme (ECE-1): three isoforms with distinct subcellular localizations.

Endothelin-converting enzyme 1 (ECE-1) is a membrane-bound metalloprotease that catalyses the conversion of inactive big endothelins into active endothelins. Two different isoforms (ECE-1a and ECE-1b) have previously been identified for human ECE-1. In the present study we have cloned a novel human ECE-1 isoform, termed ECE-1c, and have thus shown for the first time the existence of three distinct ECE-1 isoforms. The three isoforms differ only in their N-terminal regions and are derived from a single gene through the use of alternative promoters. Ribonuclease protection experiments revealed that, although the relative levels of the three isoform mRNA species vary between human tissues, ECE-1c mRNA is generally the predominant isoform messenger. Immunofluorescence microscopy analysis showed distinct subcellular localizations for the three isoforms: whereas ECE-1a and ECE-1c are localized at the cell surface, ECE-1b was found to be intracellular and showed significant co-localization with a marker protein for the trans-Golgi network. We determined that the three isoforms have similar kinetic rate constants (Km, kcat and Vmax) for the processing of big endothelin 1 and that the big endothelin isoforms 1, 2 and 3 are cleaved with similar relative velocities of 1.0:0.1:0.1 by the three isoenzymes.

Amino Acid Sequence↗

Effect of phosphoramidon (endothelin converting enzyme inhibitor) and BQ-123 (endothelin receptor subtype A antagonist) on blood pressure in hypertensive rats.

We reported previously that the endothelin converting enzyme (ECE) inhibitor phosphoramidon lowers mean arterial pressure (MAP) when infused in conscious, spontaneously hypertensive rats (SHRs). In this study we determined the dose-response relationship for this action in SHRs and in a high-renin hypertensive model, the renal artery-ligated rat. We also determined whether the ETA receptor antagonist BQ-123 (cyclo [D-Trp-D-Asp-Pro-D-Val-Leu]) might lower MAP in hypertensive rats. Phosphoramidon lowered MAP by 9 +/- 4, 31 +/- 4, and 40 +/- 4 mm Hg after 5 h when infused in SHRs at 10, 20, and 40 mg/kg/h. This lowering of MAP was associated with dose-related inhibition of the pressor response to a bolus intravenous injection of big ET (1-39) at 1 nmol/kg. BQ-123 also lowered MAP in SHRs (by 25 +/- 3 mm Hg), but only at a very high dose (50 mg/kg/h for 5 h). At this dose, BQ-123 blocked the pressor response to a bolus intravenous injection of ET-1 (1 nmol/kg), but the blockade was incomplete. Phosphoramidon infused in conscious, renal hypertensive rats lowered MAP by 31 +/- 9, 46 +/- 8, and 54 +/- 1 mm Hg after 5 h at 10, 20, and 40 mg/kg/h, respectively. This lowering of MAP was associated with blockade of the pressor response to big ET (1-39). BQ-123 did not lower MAP in renal hypertensive rats when infused at 30 mg/kg/h for 5 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

LacI mutation spectra following benzo[a]pyrene treatment of Big Blue mice.

The mutation spectrum of the lacI gene from the liver of C57Bl6 Big Blue transgenic mice treated with benzo[a]pyrene (B[a]P) has been compared with the spectrum of spontaneous mutations observed in the liver of untreated Big Blue mice. Mice were treated with B[a]P for 3 days followed by a partial hepatectomy one day after the last injection. Liver tissue was removed for analysis at hepatectomy and, again, 3 days later at the time of sacrifice. Earlier, we reported that the lacI mutant frequency in these B[a]P-treated mice was elevated in the liver both at the time of hepatectomy and at sacrifice; however, a statistically significant increase in the mutant frequency was observed only at sacrifice. In this study, the DNA sequence spectra of lacI mutations observed in the liver of B[a]P-treated Big Blue mice at hepatectomy and at time of sacrifice were compared with each other and with the spectrum of spontaneous liver mutations. No differences were observed between the two B[a]P-treatment spectra. However, mutation frequencies of both GC-->TA and GC-->CG at the time of hepatectomy and at sacrifice were significantly elevated compared with the spontaneous frequency of these same transversions. Also, the frequency of AT-->TA transversions was significantly higher than the spontaneous frequency at the time of hepatectomy but not at sacrifice. The frequency of all other classes of mutations scored was not significantly different from the frequency of these same events in the spontaneous spectra. These data support the view that B[a]P treatment results in the induction of GC-->TA and GC-->CG transversions within 1 day of the last injection and they provide insights regarding the relative roles of benzo[a]pyrene-7,8-diol-9, 10-epoxide and radical cations of B[a]P in B[a]P-induced mutagenesis in vivo. Finally, these data provide evidence for B[a]P-induced mutagenesis under conditions where no statistical increase in mutant frequency could be shown.

Animals↗

How big is the universe of exons?

If genes have been assembled from exon subunits, the frequency with which exons are reused leads to an estimate of the size of the underlying exon universe. An exon database was constructed from available protein sequences, and homologous exons were identified on the basis of amino acid identity; statistically significant matches were determined by Monte Carlo methods. It is estimated that only 1000 to 7000 exons were needed to construct all proteins.

Amino Acid Sequence↗