[Functional capacity of patients over 65 according to the Katz index. Reliability of the method]. To find functional capacity of elderly patients by using the Katz Index, which measures the "Basic Activities of Daily Life". To examine how reliable the Katz Index is in the Primary Care field. Descriptive crossover study. Assessment of the measuring instrument's internal consistency and reliability, using a test-retest method. SITE. Otero Health Area, in Oviedo. This was a random sample, ordered by age and gender, of people over 65 who used the Otero Health centre. The elderly population made up 12.86% of our base Health Area. The Katz Index showed that 81.6% of the elderly in the sample were independent in all their functions. A significant age difference was found. Internal consistency was measured by Cronbach's Alpha and was 0.8612 for nurses and 0.8362 for doctors. The correlation coefficient within Sperman's estimated observer was r = 0.936074. Kappa was 0.8436 (p < 0.0000) for the different observers, i.e. nurses or doctors. Most of the elderly patients in our base Health area possess full functional capacity, at the level of the routine activities of their daily life. The Katz Index is a reliable method of evaluating elderly peoples' functional capacity, at the Primary Care level. It can be used by any professional in the health team.


[Calibration and safety of sphygmomanometers in health centers of Murcia]. To find the levels of calibration, safety and physical faults in the sphygmomanometers used in Health Centres. A multi-centre, observational, descriptive and crossover study. SITE. 7 Health Centres in the urban zone of Murcia and nearby towns. All the sphygmomanometers in the 7 Health Centres, that is 80 aneroid and 62 mercury ones. It needs high-lighting that 43.7% of the aneroid sphygmomanometers and 12.3% of the mercury ones were wrongly calibrated. We noted that 20% of the measurements made with wrongly calibrated aneroid sphygmomanometers had a margin of error above +/- 8 mmHg, with a tendency towards under-registering. We found very significant differences between the average arterial pressure measured by aneroid instruments as against mercury ones (p < 0.001). The number of sphygmomanometers which show a margin of error greater than +/- 3 mmHg at every level of pressure is significantly greater in aneroid instruments than in mercury ones (p < 0.001). We found physical faults in 23.9% of the instruments. We consider the number of wrongly calibrated aneroid sphygmomanometers to be excessively high. Therefore mercury ones should be used whenever possible and particularly during diagnosis and treatment. Both aneroid and mercury sphygmomanometers should be regularly checked, using a proper procedure. Mercury instruments set at zero are correctly calibrated and can be used as a model for checking aneroid ones.


[Oral-dental hygiene habits in 12-year-old schoolchildren of the city of Huesca]. To study dental hygiene habits and their relationship to dental caries. A descriptive epidemiological crossover study, based on observation. SITE. Schools in the city of Huesca. Every child in the 7th grade (i.e. 12 years old) of Basic General Education (EGB) in the city of Huesca. We found that only 43.83% of the children (689 in all: 340 male, 349 female) brushed their teeth every day. 49.20% had had a dental check-up during the previous year. We noted a significant link between cariogenic factors, especially those to do with tooth-brushing and the consumption of sweets, and the actual existence of caries. There was a notable lack of dental hygiene, both around the questions of using a tooth-brush and in eating habits. There was little primary (the use of fluorides or dental hygiene) or secondary prevention (programmes of odonto-stomatologic care).


[Postvaccinal reactions to simultaneous administration of the triple viral, oral polio and diphtheria-tetanus vaccines compared with their administration in sequence]. To compare the frequency and characteristics of post-vaccination reactions, between on the one hand the simultaneous administration of the Oral Antipolio (OP), the Triple Virus (TV) and the Anti-Diphtheria and Anti-Tetanus (DT) vaccines; and on the other hand, their administration in sequence. Prospective study with interventions, with a non-random, non-blind determination. SITE. Survey covering the mothers of infants vaccinated at 24 vaccination centres in Mála province. 490 infants vaccinated during their second year of life. 263 had the vaccines administered simultaneously and 227 in sequence. Simultaneous administration of the TV, OP and DT vaccines at 15 months; as against the administration of TV at 15 months, followed by OP and DT at 18 months. 78 infants (29.66%) suffered a reaction that could be attributed to the vaccination after the simultaneous administration of TV, OP and DT; and 86 infants (37.88%) after one of the two occasions of vaccination in the administration in sequence: 27.31% after the TV, 17.18% after the OP-DT and 6.62% after both. The safety of simultaneous administration, taken together with data coming from other studies on its immunogenic effectiveness, reaffirms the usefulness of simultaneous administration of TV, OP and DT vaccines at 15 months, as a strategy to improve vaccine coverage of infants in their second year of life.


[Active pulmonary tuberculosis in the community. Current presentation]. To discover how patients in a provincial general hospital, diagnosed as having pulmonary tuberculosis had first clinically and radiologically presented. This was a retrospective observational study. SITE. The San Jorge de Huesca General Hospital. The period of study was between January, 1986, and December, 1989. Those studied were the 59 patients diagnosed as having active pulmonary tuberculosis during the study period. The average age of the patients was 45.6 +/- 19.25 SD. There was greater occurrence in males. The most common form in which the disease first appeared was thoracic symptomatology (59%), followed by constitutional syndrome (45.7%). 8 patients were addicted to drugs taken parenterally (ADVP), of whom 4 were HIV-positive (6.8%). The most common radiological pattern was ulcero-caseous. We underline the importance of diagnostical awareness at the Primary Care level in order to rapidly begin the correct treatment; and thus fight the adverse epidemiological situation caused by tuberculosis today.


[Smoking in primary schools].

[Smoking in primary schools]. To analyze policies related to tobacco use in primary schools. Cross-sectional study. SITE. Primary schools in the city of Barcelona, Spain. Schools principals of a representative sample of the 493 primary schools in the city; 98 of the 100 selected schools participated. Schools are aware of the existing regulations in Catalonia. Although there is no smoking in classrooms--which represents an improvement compared with previous years--, visible use of tobacco by adults is frequent. Usually there is no formal policy on smoking. No smoking signs are rare, and usually there is no designated person with responsibilities for the enforcement of smoking policies. Schools rarely address smoking outside school hours, and adults are often allowed to smoke in the court, the dining room or the aisles. There are no significant differences between public and private schools. Although an improvement can be seen compared to the previous situation, smoking is still visibly present in schools. There must be specific prevention projects if schools are to have a positive influence in the social perception of smoking by schoolchildren.


[Factors influencing neurological care]. To analyse certain factors which contribute to the existing backlog in specialised neurological care, such as: where the patient was referred from, the reason for the appointment, tests carried out and the final diagnosis. We used a random sample of patients. Retrospective study of patients referred from Primary Care, who were attended as out-patients in the Neurology clinic during 1991. SITE. Health Area 2 of the Autonomous Community of Madrid. The average number of patients per doctor sent from each one of the seven Centres studied was 7.69, with outliers of between 2 and 21, with a standard deviation of 3.95 and a rate of 51.31%. The proportion of new patients to patients having follow-up checks was 2 to 3, respectively. The differences between the number of patients sent from the different centres were found in the less serious pathologies. We suggest that the criteria used by Primary Care professionals and specialists should be strengthened and unified. This was one of the factors which weighed most on the quality and backlog of care.


[Evaluation of the quality of care at a nursing station in a health center]. To analyse the procedures in the care of patients who attend the nursing station (NS), identify possible faults and evaluate the effect of these procedures on the patients. Descriptive and retrospective study concerning the quality of the NS. SITE. Primary Care. At the Molino de la Vega Health Centre, Huelva. The 602 people who attended the NS: patients with Hypertension, Diabetic, Obesity and osteoarticular problems. 54.4% of the procedures show a high level of control: in the case of Hypertension, the percentage reaches 62.7% (C.I. 95%: 57.8-68%). 87.3% of diabetics treated with insulin managed to give themselves their injections. 45.4% of patients suffered more than one chronic illness. The analytical tests envisaged were carried out on 62% of those with light Hypertension and on 41.4% of those with severe Hypertension. 71.3% of patients with light Hypertension had a high rate of attendance at the station, which was correct in 93.8% of the severe cases. All categories of patients with diabetes attended with excessive frequency. The high level of control attained clearly shows the NS's usefulness. The high percentage of self-injection achieved means that the majority of our diabetics who are treated with insulin are responsible for their own health. A fair number of patients present varied pathologies. Over-use of the NS by the large proportion of those patients with light Hypertension and diabetes implies inadequate care for other groups of patients, for example those suffering severe Hypertension.


[Aneurysm of the abdominal aorta].

[Aneurysm of the abdominal aorta]. Three clinical cases of Aneurysm in the abdominal Aorta are presented, in order to make a clinical review of aneurysms in the abdominal Aorta (AAA) and underline the importance of their early diagnosis in Primary Care, given the risk factors. A retrospective, descriptive analysis of three cases of AAA from 1991. SITE. The patients studied had attended the hospital emergency department in the Alcoy Health area. Case 1: A patient, who attended because of three days of bilateral lumbar pain of a colic type spreading to the mesogastrium, which did not respond to treatment for nephritic colic. The patient died in a few hours, with the diagnosis of hypovolaemic shock caused by a burst AAA. Case 2: A patient with generalised continuous abdominal pain, which over 12 hours had been located in the lower right hemiabdomen, who was admitted with the provisional diagnosis of acute pyelonephritis. Case 3: A patient who, after an emergency surgical intervention where the diagnosis of AAA was confirmed, presented after a month a clinical picture consistent with a cerebral vascular accident and died afterwards because of renal failure. Given the present increase of patients diagnosed in hospital as suffering AAA in our Health Area, we urge that special attention be paid to the early diagnosis of this pathology. It is important to look actively for this pathology in patients with chronic pathologies of high prevalence and include it in Primary Care preventive programmes.


Cloning and expression of midecamycin 4"-acylase gene in spiramycin producing strains. A recombinant plasmid p66B containing the midecamycin 4"-acylase gene was obtained by cloning this gene into plasmid vetor pIJ680 from the primary clone pCN6C5, presumably harboring the midecamycin biosynthetic gene. The expression of the midecamycin 4"-acylase gene (p66B) in spiramycin producing strains resulted mainly in the production of 4"-isovalerylspiramycin. Another positive clone pCN10F5 was discovered from the genomic library of S. mycarofacians 1748 by probing with p66B DNA BamHI-BamHI 2.3kb fragment. A BamHI-BamHI 8.0kb homologous region on pCN10F5 was determined by Southern hybridization and was subcloned into plasmids pWHM3 and pIJ680. Recombinant plasmids pWF5 and p6F5 with molecular size about 15.2kb and 13.3kb, respectively, were obtained. Transformation of spiramycin producing strains with these plasmids resulted in the production of two major components. Based on their physicochemical properties and spectral evidences, component I was identified as 4"-propionylspiramycin III, and component II as 4"-propionylspiramycin II. Southern hybridization confirmed that the BamHI-BamHI 8.0kb fragment was cloned in the spiramycin producing strain. Only pCN10F5 clone was identified from the genomic library of S. mycarofaciens 1748 when the 4"-isovaleryltransferase gene of carbomycin producing strain S. thermotolerans was used as a probe in colony hybridization. It suggests that there is a difference between the 4"-acyltransferase genes in the pCN6C5 and pCN10F5 clones.


Restriction mapping and localization of GL-7-ACA acylase gene. This paper presents the results about the restriction mapping of recombinant plasmids pMR5 and pMR6 containing GL-7-ACA acylase gene from Pseudomonas sp. 130, gene localization and its expression under the control of different promoters, tet, tac or lac/tac, in Escherichia coli. The analysis of gel electrophoresis of pMR5 cleaved with several kinds of restriction enzymes indicated that there is no sites of EcoRI, HindIII and ClaI but the presence of following sites: one HpaI, two XhoI, three EamHI and four PstI on the cloned gene fragment. The restriction maps of pMR5 and pMR6 were determined by comparative digestion of various endonucleases. The gene of GL-7-ACA acylase was localized on a 3.0kb fragment of B2-B3-HpaI from the studies on a serial subcloning. Expression of subclones pMR9, pMR10 and pMR11 in E. coli was compared. Higher yield of acylase was obtained when the gene fragment was placed downstream of the tac promoter. The expression of Pseudomonas gene in E. coli was also discussed.


Significance of the 56th tyrosine on cytotoxic activity of tumor necrosis factor. After using site-specific mutagenesis a conserved amino acid residue, the 56th tyrosine in human tumor necrosis was substituted by glutamine. The expression level of the mutant protein in E. coli did not changed significantly, however, its specific activity of the cytotoxicity on L929 cultural cells was decreased to 1/583 of that of the unmutant tumor necrosis factor. The results show that the 56th tyrosine residue or the region where tyrosine 56th located is important for the cytotoxic activity of tumor necrosis factor.


The reverse DNA sequencing using Bst DNA polymerase. The reverse DNA sequencing (RDS) [1] is a rapid method used to check the DNA sequences by sequencing them from the opposite orientation. Because the RDS is basically a double stranded sequencing, the quality of the sequence patterns so obtained generally is not as good as those obtained by the single stranded sequencing, and extra bands and higher background are produced more frequently. This paper shows that the RDS could now generate as good sequence patterns as those obtained by sequencing on the single stranded DNA template if Bst DNA polymerase instead of the conventional enzymes, such as the Klenow enzyme, was used in the RDS. Bst DNA polymerase is heat stable (optimum reaction temperature 65 degrees C) and has recently been successfully used in the conventional DNA sequencing. The RDS has recently been further simplified to meet the need of large DNA sequencing projects such as the human genome project. The combination of the simplified RDS and the use of Bst polymerase should be expected to facilitate greatly the work on sequence confirmation and correction.


Electrofusion of protoplasts from Porphyra haitanensis and P. yezoensis thalli (Rhodophyta). In this paper the electrofusion of protoplasts from P. haitanensis and P. yezoensis thalli by using an electrofusion instrument (Shimadzu Company, Japan) under different conditions of AC field, DC pulse, fusion buffer solutions and concentrations of protease are described. The results showed that the fusion rate could reach 21-31% by applying AC field of 30-35V for 25-30s and DC pulse of 300-350 V for 60 microseconds and in the presence of 3 mM Ca2+ and 3 mM Mg2+ in the fusion buffer. The pretreatment with protease had a positive effect on cell fusion. The fusion cells formed cell walls after 7 day's culture and grew into cell aggregates after 41 day's culture.


Production of monoclonal antibody in hollow fiber culture system with serum-free medium. Hybridoma cells 7E8, secreting mouse monoclonal antibody (McAb) IgG against potato virus X, were cultured in hollow fiber cell culture system (module VF-2) with serum-free medium 1640SFM. The maximum viable cell density was found to be 2.34 x 10(6) cells/ml that was 3.7 and 2.2 times as high as those achieved in spinner and static flask culture respectively. About 10,000ml of cell culture media had been collected in the cultural period of 42 days. The ELISA titer of the McAb in the media was about 1:20,000 that was 25 times as high as those attained from the cultures in either spinner or static flask. From 1,000ml of cell culture media, an amount of 51.2mg of 7E8 McAb IgG had been purified by 50% saturated ammonium sulfate precipitation and Sephadex G-200 chromatography. The average yield of McAb in the hollow fiber cell culture system was 12.3mg/day. The results of the study suggest that it is hopeful for hybridoma cell culture in the hollow fiber cell culture system with serum-free medium for McAb production on large-scale.


Selection of strains capable of utilizing D-xylose and cellobiose to produce ethanol by electric field-induced protoplast fusion. The protoplast fusion between Candida guilliermondii S208 (Arg-) and Saccharomyces cerevisiae 314 was induced by three pulses (18kV/cm, 10 microseconds duration) applied at an interval of 1 s with the model GH-401 Electric Induced Gene Transfer/Cell Fusion System. The frequency of appearance of prototrophic hybrids was 3.6 x 10(-3). Stable fusion products were obtained after continual subculture over 20 times on selected and unselected media. Comparative studies showed that the fusion products were real hybrids of both parents. Two fustants, F-106 and F-308, could ferment both D-xylose and cellobiose to ethanol. The ethanol production of F-106 in the media containing 2% D-xylose or 2% cellobiose were 3.1g/l and 1.05g/l, respectively. The ethanol production of F-308 in the above media were 0.2g/l and 2.8g/l, respectively.


The suspension culture of Tripterygium wilfordii. In suspension culturing of Tripterygium wilfordii, 18.4 mg/l of dry cells and 9.184 mg/l of diterpene-lactone compounds were obtained from 6,7-V liquid medium containing 1 mg/l NAA. Besides those within the cells, diterpene-lactone compounds were also found in the cultured liquid and the yield reached 30.16-43.14% of the total yield. The total yield of diterpene-lactone compounds in suspension culture (6,7-V medium containing 1 mg/l NAA) was 12.19 times as much as that in the roots of the original plant. In addition, 3 samples of diterpene-lactone extracts from the suspension culture were found toxic to KB cells. Compared with those in solid culture, less incubation time was needed and more diterpene-lactone compounds were produced in suspension culture.


Analysis of the effectiveness of proline substitutions and glycine replacements in increasing the stability of phage T4 lysozyme. It was previously shown that the two replacements Gly 77-->Ala (G77A) and Ala 82-->Pro (A82P) increase the thermostability of phage T4 lysozyme at pH 6.5. Such replacements are presumed to restrict the degrees of freedom of the unfolded protein and so decrease the entropy of unfolding [B. W. Matthews, H. Nicholson, and W. J. Becktel (1987) Proceedings of the National Academy of Science USA Vol. 84, pp. 6663-6667]. To further test this approach, three additional replacements--G113A, K60P and A93P--have been constructed. On the basis of model building, each of these three replacements was judged to be less than optimal because it would tend to introduce unfavorable van der Waals contacts with neighboring parts of the protein. The presence of such contacts was verified for G113A and K60P by conformational adjustments seen in the crystal structures of these mutant proteins. In the case of G113A there are backbone conformational changes of 0.5-1.0 A in the short alpha-helix, 108-113, that includes the site of substitution. In the case of K60P the pyrrolidine ring shows evidence of strain. The thermal stability of each of the three variants at both pH 2.0 and pH 6.5 was found to be very close to that of wild-type lysozyme. The results suggest that the procedure used to predict sites for both Xaa-->Pro and Gly-->Ala is, in principle, correct. At the same time, the increase in stability expected from substitutions of this type is modest, and can easily be offset by strain associated with introduction of the alanine or proline. This means that the criteria used to select substitutions that will increase thermostability have to be stringent at least. In the case of T4 lysozyme this severely limits the number of sites. The analysis reveals a significant discrepancy between the conformational energy surface predicted for the residue preceding a proline and the conformations observed in crystal structures.


Flexible-geometry conformational energy maps for the amino acid residue preceding a proline. Previously calculated conformational energy maps suggest that the alpha-helical conformation for the residue preceding a proline is disfavored relative to the extended conformation by more than 7 kcal/mol. In known protein structures this conformation is observed, however, to occur for about 9% of all prolines. In addition, introduction or removal of prolines at theoretically unfavorable positions in proteins and peptides can have modest effects on stability and structure. To investigate the discrepancy between calculation and experiment, we have determined how the conformation of the proline affects the calculated energy. We have also explored the effect of bond length and bond angle relaxation on the conformational energy map. The conformational energy of the preceding residue is found to be unaffected by the conformation of the proline, but the effect of allowing covalent bond relaxation is dramatic. If bond lengths and angles, and dihedral angles within the pyrrolidine ring, are allowed to relax, a calculated energy difference between the alpha and beta conformations of 1.1 kcal/mol is obtained, in reasonable agreement with experiment. The detailed shape of the calculated energy surface is also in excellent agreement with the observed conformational distributions in known protein structures.


DNA torsional dynamics by multifrequency phase fluorometry. The time decay of the fluorescence polarization anisotropy of calf thymus DNA-ethidium complexes is obtained from measurements with sine-modulated excitation employing the so-called multifrequency phase fluorometry. A torsional dynamics model developed by J. M. Schurr [(1984) Chemical Physics, Vol. 84, pp. 71-96] and translated into the frequency domain is found here to describe accurately DNA-ethidium fluorescence data collected under modulated excitation. At a low dye/DNA ratio (1:400) the value of the DNA torsional constant (alpha = 4.63 +/- 0.2 10(-12) dyne cm) fitting the data agrees very well with the known values of alpha. When the measurements are extended to a higher ethidium/DNA ratio, energy transfer effects between intercalated dyes are observed. A theoretical prediction of the donor and acceptor dye contributions to the fluorescence polarization anisotropy is made here, taking into account also dye-dye distance distributions.


Facilitated synthesis of peptaibols: alamethicin via enzymatic segment condensation. We have used a combined chemical-enzymatic approach to facilitate the total synthesis of the 20-residue peptaibol, alamethicin. The 1-11 segment of alamethicin, having a C-terminal Gly, and the 12-20 segment, having an N-terminal Leu, were prepared by well-established chemical methods, and then coupled using papain to afford a 54% yield of alamethicin in straightforward fashion. In contrast to the reported chemical syntheses of alamethicin requiring side-chain protection at Glu,18 the papain-catalyzed coupling proceeded readily and selectively using a C-terminal segment having a free gamma-carboxyl group at this position. Several alamethicin partial sequences were obtained via enzymatic formation of the Gly11-Leu12 bond. The high efficiency of this route is illustrated by the enzymatic assembly of the 1-17 alamethicin fragment on a 400-mg scale in 62% yield. An alternative route to alamethicin through enzymatic formation of the Ala6-Gln7 bond was less successful because of a low yield in the final coupling.


Quasielastic light scattering study of thermal excitations of F-actin solutions and of growth kinetics of actin filaments. In the first part of this work we report quasielastic light scattering (QELS) studies of the internal dynamics of transient actin networks over a time range of 10(-6)-10(-2) s, scattering angles between zeta = 20 degrees and 150 degrees, and a concentration range of 0.015 (0.3) to 0.7 mg/mL (15 microM). We confirm our previous result that (1) the dynamic structure factor g(q,t) is determined by the thermally excited undulations of the actin filaments and (2) that the initial decay of g(q, t) scales as g(q, t) varies; is directly proportional to exp(-q alpha t) while the long time decay scales as g(q, t) varies; is directly proportional to exp [-(Aq alpha t) 2/3] with alpha = 2.75. The deviation of alpha from the theoretical value of alpha = 3 predicted for Rouse-Zimm chains is similar to that found for high molecular weight macromolecular solutions by QELS. A refined analysis of the dynamic structure factor showed that it can be interpreted in terms of three relaxation processes (besides the contribution of the residual monomer diffusion): (1) the dominant Rouse-Zimm dynamics, which comprises between 65 (at high concentrations) and 85% of the signal; (2) a fast relaxation process with a decay constant of gamma = 9 x 10(3) s-1, which contributes at all concentrations with the same amplitude; and (3) a nonexponential ultraslow contribution of the form g(us) varies; is directly proportional to exp [(-gamma ust)]1/4. The third contribution appears only at high concentrations and increases strongly with decreasing scattering angles. It is thus attributed to fluctuations of the mesh size of the transient actin network. In the second part we show that high sensitivity QELS may be applied to follow the actin polymerization process at low temperatures (10 degrees C). The apparent diffusion coefficient and the static scattering intensity of the actin filaments were determined as functions of polymerization time tpol. We show that the process consists of the rapid growth of a few filaments that become very long (approximately 10 microns; even at actin concentrations of 0.04 micrograms/mL) near the critical growth concentration of 0.012 micrograms/mL, as is expected for a growth process determined by nucleation. Finally, we studied actin networks polymerized in the presence of complexes of gelsolin with actin. By application of the CONTIN program we could determine the length distribution of the filaments.(ABSTRACT TRUNCATED AT 400 WORDS)


Monte Carlo calculations of ion distributions surrounding the oligonucleotide d(ATATATATAT)2 in the B, A, and wrinkled D conformations. We calculated the uni-univalent ion distributions around the oligonucleotide d(AT)5.d(AT)5 in the A, B and wrinkled D conformation using the Metropolis Monte Carlo method. All atoms were included in the oligonucleotide model with partial charges and hard sphere radii assigned to each atom. The univalent counter- and coions were modeled as hard spheres with radius 0.3 nm. The solvent was assigned a dielectric constant of 80, corresponding to a temperature of 298K. The counterion distribution surrounding each of the conformers and the distribution surrounding an impenetrable cylinder, were calculated for four salt concentrations. We found significant counterion density in the major groove of the A DNA while fewer counterions occupied the grooves of B DNA. In the wrinkled D DNA, where groove occupancy is sterically hindered, the ion distributions were identical to the distributions surrounding the impenetrable, cylindrical model. This suggests that excluded volume effects significantly influence the details of the ion distributions near the oligomer, while the detailed charge distributions of the oligomer affects the ion distributions only minimally. Although substantial variation in counterion density was observed near the oligomers of differing conformations, the total number of counterions located within a cylinder surrounding the oligomer bounded radially by 2.4 nm was independent of the conformation of the oligomer. Therefore, for this model system, the local univalent counterion distributions are extremely sensitive to the geometry of the oligonucleotide whereas the extent of neutralization of the oligoanion is insensitive to the conformation of the oligomer.


A synthetic analogue for the active site of plant-type ferredoxin: two different coordination isomers by a four-cys-containing [20]-peptide. The (Fe2S2)2+ complex of an artificial 20-peptide ligand, Ac-Pro-Tyr-Ser-Cys-Arg-Ala-Gly-Ala-Cys-Ser-Thr-Cys-Ala-Gly-Pro-Leu-Leu-T hr-Cys- Val-NH2, containing an invariant Cys-A-B-C-D-Cys-X-Y-Cys (A, B, C, D, X, Y = amino acid residues) fragment of plant-type ferredoxins was synthesized by a ligand exchange method with [Fe2S2(S-t-Bu)4]2-. 1H-nmr spectroscopic and electrochemical data of the complex indicate the presence of two coordination isomers. One of them having a Cys-X-Y-Cys bridging coordination to the two Fe(III) ions, has the (Fe2S2)2+ core environment similar to those of the denatured plant-type ferredoxins and exhibits a positive shifted redox potential at -0.64 V vs saturated colonel electrode (SCE) in N,N-dimethylformamide (DMF). Another isomer with the Cys-A-B-C-D-Cys bridging coordination shows a negative redox potential at -0.96 V vs SCE in DMF.


Peptide hormone-membrane interactions: the aggregational and conformational state of lipo-gastrin derivatives and their receptor binding affinity. The (2RS)-1,2-dipalmitoyl-3-mercaptoglycerol/-, (2RS)-1,2-dimyristoyl-3-mercaptoglycerol/-, and (2RS)-1-myristoyl-2-palmitoyl-3-mercaptoglycerol/maleoyl-bet a-alanyl- [Nle15]-human-gastrin-(2-17) adducts were prepared as lipo-gastrin derivatives of explicitly primary amphiphilic properties. As representative of this class of lipo-gastrins, the dimyristoyl derivative has been thoroughly characterized in its aggregational state since, among the three compounds, theoretically it should exhibit the lowest degree of lipid character. It aggregates in aqueous solution to form monodispersed unilamellar spherical vesicles with dislocation of the peptide moiety at the bilayer surface in predominantly unordered structure. The liposomes are remarkably stable toward solubilization with trifluoroethanol and toward vesicle to micelle transition with neutral and negatively charged surfactants even above their critical micellar concentrations. Asymmetric fusion with the detergent micelles induces polydispersion of the liposomes in terms of shape and size without affecting in significant manner the mode of display of the gastrin portions at the bilayer surface. Only the positively charged hexadecyltrimethylammonium hydroxide provokes the collapse of the vesicles into mixed micelles with concomitant altered dislocation of the gastrin-peptide in the new aggregational state. Despite the lipid properties of the gastrin derivatives, i.e., formation of liposomes, they retain remarkable receptor affinities (IC50 = 1.5 x 10(-9) M for myristoyl-palmitoyl-gastrin, IC50 = 2.0 x 10(-9) M for di-myristoyl-gastrin and IC50 = 3.1 x 10(-9) M for di-palmitoyl-gastrin vs IC50 = 2.8 x 10(-10) M for Nle15-gastrin). Since the displacement of radiolabeled Nle15-gastrin from rat pancreatic acinar cell line membrane preparations by both the parent gastrin hormone and the three lipo-gastrins occurs in parallel manner, the data support a mechanism of receptor occupancy via accumulation of the gastrins at the membrane surface and their two-dimensional diffusion to the target receptor. Thereby the differentiated decrease of affinity in function of fatty acid chain length has to be attributed to the energetically more or less favored transfer of the monomers from the donor vesicles to the acceptor membranes. Moreover, according to this model migration of the lipo-gastrins with their interdigitating di-fatty-acyl moieties should be delayed, again in lipid structure-dependent manner, in comparison to the parent gastrin molecule, which is free to float in the membrane interfacial phase.


Conformational perturbation of the anticancer nucleotide arabinosylcytosine on Z-DNA: molecular structure of (araC-dG)3 at 1.3 A resolution. The left-handed Z-DNA structure of an araC-containing (where araC stands for arabinosylcytosine) hexamer, (araC-dG)3, has been solved by x-ray diffraction analysis at 1.3 A resolution. This hexamer was crystallized in the hexagonal P6(5)22 (a = b = 17.96 A, c = 43.22 A) space group in which the hexamers have statistically disordered packing arrangement along the 6(5) screw axis, yet the crystals diffract x-rays to high resolution. Its structure has been refined by the constrained least square refinement to a final R factor of 0.287 using 737 [> 3.0 sigma(F)] observed reflections. The asymmetric unit of the unit cell contains only a dinucleotide, 5'-p (araC)p(dG). The overall conformation resembles that of the canonical Z-DNA, but with some differences in details. The O2' hydroxyl groups of the araC residues form intramolecular hydrogen bonds with N2 of the 5'-guanine residues. In the deep groove of Z-DNA, these hydroxy groups replace the bridging water molecules that stabilize the guanine in the syn conformation. The results reinforce the earlier observation made by the structural analysis of another hexamer, d(CG[araC]GCG), with a mono-substitution of araC [M.-K. Teng, Y.-C. Liaw, G. A. van der Marel, J. H. van Boom, and A. H.-J. Wang (1989) Biochemistry, vol. 28, pp. 4923-4928]. These two structures show that araC residue can be incorporated readily into the Z structure and probably facilitates the B to Z transition, as supported by uv absorption spectroscopic studies in a number of araC-containing oligonucleotides. The potential biological roles of the araC-modified Z-DNA are discussed.


Kinetics of folding and unfolding of beta beta-tropomyosin. The kinetics of folding from random coils to two-chain coiled coils of beta beta-tropomyosin was studied by stopped-flow CD (SFCD) in the backbone region (222 nm). Two species were studied: the reduced form and the doubly disulfide cross-linked form. The proteins were totally unfolded in 6M urea-saline buffer, then refolded by tenfold dilution into benign buffer. In the refolding medium, they spontaneously recover the two-chain coiled-coil structure. Reduced beta beta refolds in at least two stages: one or more fast phases (< 0.04 s), in which an intermediate with 71% of the equilibrium ellipticity forms, followed by a slower time-resolvable phase that completes the folding. The slow phase is first order, signifying that dimerization occurs in the fast phase. The time constant of the slow phase is 2 s at 20 degrees C and requires activation parameters of delta S not equal to = -7 +/- 0.3 cal/mol.K, delta H not equal to = 15 +/- 1 kcal/mol. These results are very similar to those previously found for the reduced genetic variant alpha alpha-tropomyosin. In contrast, refolding of doubly disulfide cross-linked beta beta is complete within the dead time (< 0.04 s), whereas the singly cross-linked alpha alpha species also displays a slow phase. The opposite process, unfolding reduced beta beta from the coiled-coil state, is complete within the dead time, as in the alpha alpha variant.


The antigen-antibody interaction algebraically interpreted as a relational process. The antigen-antibody interaction occurring previous to the triggering of the immunological response is analyzed as a relational process in terms of lattices. Accordingly, this process is expressed as a lattice belonging to a pseudo-Boolean algebraic variety. The Heyting arrow operation, which appears in this kind of algebra, is used to analyze behaviors between non-comparable biological states expressed by the lattice. The resulting states coming from the arrows are connected with the influence of increasing and decreasing energies involved in the linking process.


The uncertainty principle as an evolutionary engine. Heisenberg's uncertainty principle in quantum mechanics underlies the genesis of evolutionary variability. When the uncertainty principle is coupled with the incontrovertible principle of the conservation of energy and material resources, there appears an uncertainty relationship between local fluctuations in the quantities to be conserved on a global scale and the rate of their local variation. Since the local fluctuations are accompanied by the non-vanishing rate of variation because of the uncertainty relationship, they generate subsequent fluctuations. Generativity latent in the uncertainty relationship is non-random and ubiquitous all through various evolutionary stages from abiotic synthesis of monomers and polymers up to the emergence of behavior-induced variability of organisms.


Periodical changes of amino acid reactivity within the genetic code. Enthalpies (delta H++) and entropies (delta S++) of activation for the reaction of 18 N'-hydroxysuccinimide esters of N-protected proteinaceous amino acids with p-anisidine were measured and free enthalpies of activation (delta G++) at 25 degrees C were calculated on this basis. A regular correlation between delta G++s and the corresponding amino acid codons was found. To obtain this correlation all the codons had to be arranged in a closed ring in which the consecutive codons were connected by one-step mutational changes. One-step mutations appeared as a regular series: 2,3,3,3,1,3,3,3,1,3,3,3,1,3,3,3,2,3,3,3. (the numbers denote a codon position in which a change took place). There were three such 'one-step mutation periods' in the ring, each containing 20 codons (in each block of 16 codons with A, U and C, in the central position and 4 codons containing G in the central position). The end of the third period (UG) and the beginning of the first period were bridged by the four codons of glycine with G in the second position. The values of delta G++ change similarly in each period, increasing upon approaching Lys, Pro, and Ile. The periodical relation between the chemical reactivities of the coded amino acids (reflected by delta G++s) and the structure of their codons could be of importance for the origin of the genetic code i.e. for selection of proper codons for the definite amino acids.


Enzymes as molecular automata: a reflection on some numerical and philosophical aspects of the hypothesis. Enzymes, by means of their properties of specific recognition and allosteric modulation, are able to integrate many separate processes into systemic units with coherent functions; in a sense, they have to be considered as the true organizers of the cytoplasmic processes. In this respect, the present article describes a simple model, based on binary variables and automata theory, which simulates the basic regulatory performance of the modulated enzyme. The model admits a variety of modifications and improvements; it also suggests some original lines of thought on which to reflect about the organization and collective phenomena of the networks of enzymes. In discussing the connection of this 'molecular automata' hypothesis with other areas of present-day theoretical biology, a fertile panorama of initiatives appear. A special partnership between Information Science (computation) and Biology is developing.


Fibronectin promotes lung colony formation in the mouse by B16 melanoma cells spheroids. By microscopical observation and using an original method of automatic image analysis, we studied on histological sections the rate of lung colony formation after intravenous injection into the mouse of B16 melanoma cells previously cultivated in vitro as pure or mixed spheroids (B16 + 3T3 fibroblasts). The preincubation in vitro of pure spheroids with fibronectin significantly increased the percentages of lung section area occupied by tumors and the relative number of internal lung colonies. This effect of fibronectin was even more obvious when mixed spheroids were injected.


Bacterial mutagenicity of extracts of the baked and raw Agaricus bisporus mushroom. Aqueous extracts of baked and raw Agaricus bisporus (AB) mushroom were tested for mutagenic activity in Salmonella typhimurium strains TA1535 and TA1537. The extracts were studied with and without metabolic activation by Aroclor-induced rat liver S9 mix. The extracts of the baked and raw AB exhibited a dose related mutagenic activity with and without activation in strain TA1535. Similar findings were obtained in strain TA1537, although the net revertant values were of lower magnitude. Because humans mainly consume the cultivated mushroom AB in baked form, the implications of the findings are self-evident.


Anti-influenza virus activity of a lignin fraction from cone of Pinus parviflora Sieb. et Zucc. When mice were inoculated intranasally or intracerebrally with lethal doses of influenza virus A/WSN/33, most died within 12 days. However, the infectivity of virus that had been preincubated with a lignin prepared from cones of Pinus parviflora Sieb. et Zucc. (PC-Fr. VI) was significantly reduced. Intraperitoneal or oral administration of PC-Fr. VI, prior to virus inoculation, slightly increased the survival ratio of the infected mice. Experiments using radiolabeled PC-Fr. VI revealed that this fraction effectively binds to virions as well as to cultured cells. These data suggest that PC-Fr. VI either inactivates the virus or induces the anti-viral state in cells by binding to virions or cells.


Effects of a human urinary kininogenase (SK-827) on cerebral microcirculation after glass bead-induced cerebral embolism in rabbits. The pharmacological effects of a human urinary kininogenase (SK-827) on the cerebral microcirculation were studied intravital-microscopically in a rabbit with cerebral microvessel injury induced by glass bead injection into an internal carotid artery. Intravenous administration of SK-827 dilated pial arteries of the brain and increased cerebral hemoglobin content (IHb). SK-827 tended to dilate smaller arterioles more markedly than larger arterioles, and larger arterioles than small arteries. SK-827 appeared to have a vasodilating effects qualitatively different from those of nicardipine and CDP-choline. Findings obtained by concurrent hematological and biochemical examinations also suggested its beneficial effects on the function of platelets and erythrocytes.


Suppressive effect of vitamin E on lipid peroxidation in halothane-administered guinea pig liver. The effect of vitamin E on halothane-induced liver damage was studied in guinea pig halothane hepatitis. Twenty animals were divided into 3 groups, consisting of a control group, a halothane group and a vitamin E + halothane (H) group. The animals in the control group (n = 6) were allowed to inhale air only. The animals in the halothane group (n = 6) and the vitamin E + H group (n = 8) were allowed to inhale 1% halothane with air. Animals in the vitamin E + H group were additionally injected with 30 mg kg-1 of vitamin E 30 minutes prior to inhalation of halothane. Blood was aspirated from the heart immediately after sacrificing to measure the serum activity of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT). A microsomal suspension was prepared from the excised liver. Then the amount of thiobarbituric acid (TBA) reactive products in the microsomes were measured. The amount of tissue TBA-reactive products was increased by inhalation of halothane. The increase in the amount of TBA-reactive product was inhibited by the administration of vitamin E. The serum GPT activity was increased by halothane inhalation. Increased serum GOT and GPT activity were inhibited by the administration of vitamin E. These results demonstrated that vitamin E suppressed halothane-induced liver damage in the guinea pig by inhibiting lipid peroxidation.


Changes in the chicken bursa of Fabricius and immune response after treatment with melatonin. Since melatonin causes considerable reduction in the thymic weight of chickens, the aim of the present study was to find out whether the bursa of Fabricius and the immune response are also affected by this substance. The results show that melatonin also acts on the bursa of Fabricius depending upon the administration route. When injected subcutaneously it does not reduce bursal weight and the histological pattern does not change, while primary and secondary immune responses are significantly lowered. When melatonin is introduced into the bursa, it causes a considerable decrease in bursal weight and the histological pattern is greatly modified. A significant reduction in antibody production is observed involving the primary immune response alone. Transmission electronic microscopy seems to show that melatonin affects the reticulo-epithelial (REp) cells.


Thirty day genotoxicity study of an organophosphate insecticide, monocrotophos, in a chick in vivo test system. The genotoxicity of an organophosphate insecticide, monocrotophos, was evaluated upon chronic exposure in a chick in vivo test system employing micronucleus bioassay. In this study the animals were treated once daily for 30 days. The induced frequency of micronuclei in the erythrocytes of both bone marrow (BM) and peripheral blood (PB) were significantly higher than the respective control values. Weekly recording of the body weight of treated and control groups did not reveal any significant effect of the chemical on the general growth rate. The present results revealed the genotoxic potential of monocrotophos and also substantiate our earlier suggestion regarding the suitability of the chick in vivo test system to screen environmental abuses for mutagenicity.


Monocyte release and plasma levels of interleukin-6 in patients irradiated for cancer. Interleukin-6 (IL-6) release from purified blood monocytes was determined in patients with breast cancer or prostatic cancer before and after radiation treatment (Rx). Plasma levels of IL-6 and neopterin were also determined. Spontaneous IL-6 release in vitro was higher in breast than in prostatic cancer or in controls. Strong lipopolysaccharide (LPS)-induced cellular IL-6 release was detected in breast cancer and controls but was subnormal in prostatic cancer. Addition of indomethacin to cultures had no effect on IL-6 release. Rx generally increased levels of in vitro released IL-6 and raised LPS-stimulated IL-6 secretion in prostatic cancer to normal. Plasma levels of IL-6 were lower in breast than in prostatic cancer or controls. Rx resulted in a tendency towards raised levels in both patient groups suggestive of monocyte activation. In accordance with this, plasma levels of neopterin, which were normal before treatment, increased in prostatic cancer patients after Rx. Taken together, the results of this study indicate that monocyte release as well as plasma levels of IL-6 are affected by the malignant state as well as by radiation treatment. In view of the antiproliferative effects of IL-6, the findings may have bearing on the pathogenesis and treatment of malignant disease.


Intraperitoneal injection of dipyridamole increases the life span of tumor bearing mice treated with fluorouracil. This study was carried out to investigate the effect of the Fluorouracil (5-FU) and Dipyridamole (DP) combination on the growth of P388 murine lymphoid neoplasms. The first stage was to determine the lethal dose (LD 50) for each compound (5-FU, DP) to normal B6D2F1 mice after intraperitoneal (i.p.) injection. The LD 50 were 700 and 54 mg/kg for DP and 5-FU respectively. B6D2F1 mice bearing P388 ascitic tumors and receiving a 4-day schedule of 5-FU (2 mg/kg/day) with DP (100 mg/kg/day) 1 hr before each 5-FU dose were studied. DP was found to lower significantly (p < 0.0001) the mortality of 5-FU in tumor bearing mice by nearly 2.5 fold. This study aims at defining the best dose combination of intraperitoneal injection of 5-FU in conjunction with DP. These data allow a prospective evaluation of 4-day, i.p. 5-FU and DP with an increase of life span without toxic death.


Coronary artery disease is the major determinant of excess mortality in patients with insulin-dependent diabetes mellitus and persistent proteinuria. The goal of this review was to assess the magnitude of coronary artery disease (CAD) mortality and its determinants in insulin-dependent diabetes mellitus (IDDM) patients with persistent proteinuria. By reanalyzing data from two previously published studies of patients with nephropathy, it was found that these patients had extremely high CAD mortality rates in comparison with IDDM patients without proteinuria, but only after the age of 35 yr. In addition, the risk of CAD death was associated with high serum cholesterol levels but was unrelated to systemic blood pressure, smoking habits, and obesity. Further studies of the determinants of CAD in patients with IDDM and proteinuria are urgently needed. Except for efforts to lower serum cholesterol, it is not known whether any other measure can be undertaken to reduce the extremely high mortality due to CAD that afflicts IDDM patients with persistent proteinuria, in particular those patients whose renal failure might have been "successfully" postponed by antihypertensive therapy.


Cost-effectiveness of screening and early treatment of nephropathy in patients with insulin-dependent diabetes mellitus. Studies have demonstrated that "antihypertensive" treatment with angiotensin-converting enzyme inhibitors (ACEI) may retard the progress of nephropathy in patients with insulin-dependent diabetes mellitus. To obtain an indication of the potential effect of ACEI treatment and as a guide to future research, the effects of screening and early ACEI treatment programs were estimated using cost-effectiveness models. The preliminary analysis suggests that the early treatment of insulin-dependent diabetes mellitus patients with ACEI is likely to be a very cost-effective use of health care resources. The cost-effectiveness ratio for screening and treatment at the stage of microalbuminuria ($7,900 to $16,500 per year of life saved) compares favorably with those of other medical life-saving interventions. Less-aggressive programs (screening followed by treatment at the stage of proteinuria) would improve life expectancy to a lesser extent but could save net health care costs as well as years of life. Although more exact and comprehensive cost-effectiveness analysis must await clinical trials, these illustrative results demonstrate the range of cost-effectiveness that can be expected from these programs and identify data needed for more decisive policy conclusions.


Improved efficacy of doxorubicin by simultaneous treatment with interferon-gamma and interleukin-2. Doxorubicin (DOX) is a potent anticancer agent active against a wide range of human neoplasms, yet, as is characteristic of most chemotherapeutics, the treatment of cancer with DOX alone has met with only limited success. This study was designed to investigate the possibility that the therapeutic potential of DOX could be enhanced by combination with one or more biological response modifiers. Segments (1mm3) of a transplantable colonic adenocarcinoma were implanted into the hind limbs of male WAG rats (200-250g). Serial tumour measurements were taken 3 x weekly throughout the 4 week experimental period by measuring the longest and perpendicular lengths with calibrated calipers. All drug administration was via a chronic indwelling jugular catheter, commencing 12 days after tumour implant, with control animals receiving physiological saline. Treatment of animals with DOX (4.5mg/kg as a 15 minute i.v. infusion), interferon gamma (IFN-gamma) (5 x 10(5) U/kg/day bolus i.v. for 5 days) or interleukin-2 (IL-2) (1 x 10(5)U/rat/day continuous i.v. infusion for 5 days) retarded tumour growth by approximately 30% by the completion of the study period (P < 0.001). The combined administration of IFN-gamma with DOX did not significantly alter the antitumour activity of either DOX or IFN-gamma. Concurrent administration of IL-2 with DOX also showed this treatment to have no therapeutic activity over that achievable with either agent alone. However, treatment of animals with IL-2, IFN-gamma and DOX resulted in a significant increase in tumour growth inhibition compared to DOX with either single cytokine (P < 0.001) and this was achieved without any apparent increases in the gross toxicity of DOX.(ABSTRACT TRUNCATED AT 250 WORDS)


Hypertension and the development of complications in patients with non-insulin dependent diabetes mellitus in Japan. Hypertension is a very frequent condition in individuals with non-insulin dependent diabetes mellitus (NIDDM) in Japan and has affected the occurrence of late diabetic complications, especially stroke and nephropathy. Despite similar characteristics of hypertension among Japanese and white patients, the effect of hypertension on the development of coronary artery disease (CAD) in these two populations is strikingly different. In white NIDDM patients, hypertension is one of the major risk factors for the development of CAD. However, CAD is an infrequent complication in NIDDM patients in Japan, even though they have hypertension, lipid abnormalities, and renal complications.


Hypertension and coronary artery disease in non-insulin dependent diabetes--cause and effect? There is a log-linear increase in the risk of coronary heart disease with elevation of levels of blood pressure. Allowing for the phenomenon of regression dilution bias, this corresponds to around a 20 to 25% increase in risk for each 5 to 6 mm Hg elevation in usual diastolic blood pressure. In diabetic subjects, a similar relationship occurs, but of somewhat lesser degree. Recent overviews of therapy suggest that in nondiabetics, reducing blood pressure reverses around 50% of the excess coronary heart disease risk, but this has not yet been conclusively shown in patients with diabetes. The reduction in risk with therapy is a prerequisite to defining the antecedent as a causal influence on outcome, but it is as likely that the incomplete reversibility of excess risk represents other pathways of connection between hypertension and coronary heart disease as a consequent of iatrogenic effects of current treatments. Several alternative mechanisms are outlined, and the suggestion is made that only in the context of randomized controlled studies could the possible benefits on coronary heart disease of agents influencing such mechanisms be assessed.


Pharmacologic therapy of mild to moderate hypertension: possible generalizability to diabetics. This article reviews the evidence on pharmacologic therapy of hypertension in reducing morbidity and mortality from stroke and coronary heart disease (CHD) and considers the possible generalizability of these findings to diabetics. For malignant hypertension, benefits are large and obvious from uncontrolled case series. For severe hypertension, conclusive benefits have been shown in several randomized trials. For mild to moderate hypertension, however, it is necessary to consider meta-analyses of all individual trials. The most comprehensive of these shows reductions of 42% for total stroke (95% Cl, -33 to -50%; P < 0.0001) and 14% for all CHD (95% Cl, -4 to -22%; P < 0.01). The applicability to diabetics is unclear because they were excluded from most of the trials. The Hypertension Detection and Follow-Up Program included diabetics and reported subgroup analyses. The reduction in mortality among the actively treated diabetics of 5% was less than the 17% achieved in nondiabetics. It is unclear, however, whether the mortality reductions are truly different or reflect the play of chance. Because of the higher incidence of CHD events among diabetics with hypertension, a similar relative benefit would result in a much greater absolute risk reduction. Further, the drugs used adversely affect lipid and glucose metabolism. New antihypertensive drugs without these side effects may further improve the risk-to-benefit ratio of antihypertensive treatment, especially in diabetics, who are at a several-fold absolute increased risk or cardiovascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)


Identifying genetic determinants in human essential hypertension. Genetic factors play an important role in the pathophysiology of human essential hypertension. The remarkable success of molecular genetic techniques in identifying the basis for single gene disorders at the DNA level has encouraged investigators to apply similar techniques in an attempt to identify blood pressure genes. In contrast to single gene disorders, however, the study of blood pressure is complicated by its quantitative, complex, heterogeneous, and polygenic nature. This article examines current methods and strategies for identifying genetic determinants in human hypertension. The availability of highly polymorphic markers, the advances in quantitative trait analysis, and the mapping of blood pressure-determining genes in a polygenic rat model of hypertension suggest that molecular genetic research in human hypertension has come of age.


Histopathological changes in rat pancreas after fasting and cassava feeding. Histopathological changes in rat pancreas were induced by cyclic periods of experimental malnutrition or by cassava (manioc) feeding for 11 weeks. Decline of body weight was correlated with decrease in testicular fat pad weight as a measure of body fat stores. A marked decrease in pancreatic weight in the cassava-fed group was correlated with shrinkage of acinar structures and degenerative features in exocrine pancreas. In the malnutrition group vacuolisation and loss of tissue architecture were observed in some parts of the organ. No signs of ductal obstruction as a tentative cause of pancreatic pathology after malnutrition could be detected. Loss of islets tissue was occasionally seen in degenerative areas. It is concluded that histopathological changes in exocrine pancreas result from malnutrition and cassava feeding differentially and precede ultimate degenerative processes of pancreas endocrine tissue. Tropical malnutrition type diabetes and low protein related diabetes may in their etiology be different entities, but may coincide in practice and aggravate each other to yield severe and irreversible morbidity.


Predisposition to essential hypertension and the development of diabetic nephropathy. Only a subset of insulin-dependent diabetic patients are at risk of developing nephropathy. Prospective studies of uncomplicated insulin-dependent diabetic cohorts have shown that a rise in systemic arterial pressure is a concomitant feature of the progression to early nephropathy. The development of hypertension is an integral feature of established nephropathy in diabetes, and its amelioration retards the progression of disease and may improve overall mortality. Family studies have suggested that nondiabetic parents of insulin-dependent diabetic patients with nephropathy have a greater prevalence of hypertension, and in certain groups of non-insulin dependent patients, it has been found that the blood pressure before the onset of diabetes correlates with the development of nephropathy after the onset of diabetes. These results indicate that a propensity to hypertension may be part of the genetic predisposition to nephropathy. This contention is further supported by the finding that a raised erythrocyte sodium-lithium countertransport, a biochemical marker of hypertension and cardiovascular disease whose activity is largely genetically determined, occurs with greater frequency in proteinuric diabetic patients and their nondiabetic parents than in those diabetic patients without nephropathy and their parents. Recent family studies have also shown that a family history of cardiovascular disease significantly increases the risk of nephropathy by up to three-fold in insulin-dependent diabetes. It is suggested that the cardiorenal complications of diabetes mellitus may be linked to reduced insulin sensitivity, which itself is associated with hypertension, raised sodium-lithium countertransport rates, and cardiovascular disease.


Predisposition to essential hypertension and renal hemodynamics in recent-onset insulin-dependent diabetic patients. The offspring of essential hypertensive parents have been found to exhibit abnormalities in renal hemodynamics and sodium handling before the eventual occurrence of hypertension. The reported abnormalities represent a wide spectrum of changes including increased GFR, normal or decreased RPF, slight increase in blood pressure (although within the normal range), and an exaggerated natriuresis response to a sodium load. The heterogeneity of these abnormalities may reflect the specific conditions of the studies, the lability of the changes, or different subgroups of subjects with genetic predisposition to essential hypertension. Several lines of evidence have suggested a relationship between hypertension and the development of diabetic nephropathy in insulin-dependent diabetics. This laboratory has found that recent-onset insulin-dependent diabetics can exhibit renal hemodynamics abnormalities very early in the course of diabetes according to a positive or negative family history of essential hypertension. These changes include increased GFR and mean arterial pressure, but no differences in renal sodium and lithium handling in diabetics with a genetic predisposition to essential hypertension. In addition, diabetics with a positive family history of essential hypertension exhibited a more-marked vasodilative response to an acute interruption of the renin-angiotensin system, further suggesting inadequate angiotensin modulation of renal vascular tone. The significance of these abnormalities in relation to the development of diabetic nephropathy requires further investigation.


Sodium activation kinetics of red blood cell Na+/Li+ countertransport in diabetes: methodology and controversy. Although many studies report an elevated Vmax of red blood cell Na/Li countertransport (CTT) activity in patients with insulin-dependent diabetes mellitus (IDDM) complicated by renal disease, divergent reports exist. This article reviews the technical issues and selection criteria that fuel this controversy. In addition, new studies from this laboratory indicate that insulin in vitro and in the nonfasted state modulate CTT activity and may contribute to the discrepant findings. Incubation of red blood cells from fasted controls with physiologic concentrations of insulin induced a twofold increase in the Km for external Na+. Similarly, Na+ activation kinetics of Li+ efflux showed saturation between 50 and 150 mM Na+ in fasted controls whereas saturation, postprandially, occurred between 100 and 150 mM Na+ as a result of an increase in Km. To clarify the role of prandial status on the measurement of Na+/Li+ CTT activity in diabetes, Na+ activation kinetics were investigated in 34 nonfasting patients with IDDM. Li+ efflux was fully saturated between 80 and 150 mM Na+ in the normoalbuminuric subjects (N = 22), whereas saturation occurred between 150 and 280 mM Na+ in the patients with diabetic nephropathy (N = 14). Patients with nephropathy have higher values of Km for Na+ than do the patients free of renal complications (86 +/- 9.5 versus 41.3 +/- 3.4 mM Na+, respectively; P < 0.000012). The higher Km prevented complete saturation of Li+ efflux at 150 mM extracellular Na+ concentration and contributed to the underestimation of Vmax at 150 mM Na+ selectively in persons with renal complications.(ABSTRACT TRUNCATED AT 250 WORDS)


Close relationship between microalbuminuria and insulin resistance in essential hypertension and non-insulin dependent diabetes mellitus. The aim of this study was to investigate the relationships among insulin resistance and albumin excretion rate in 25 nondiabetic patients with essential hypertension and in 28 patients with non-insulin dependent diabetes mellitus (NIDDM). Two groups of healthy subjects matched for age, sex, and weight served as controls. Patients with essential hypertension were divided into two subgroups: without (H1) and with (H2) microalbuminuria. Diabetic patients were divided into four subgroups: those with normoalbuminuria without (NIDDM1) and with (NIDDM2) hypertension and those with microalbuminuria without (NIDDM3) and with (NIDDM4) hypertension. Whole-body glucose utilization during euglycemic hyperinsulinemic clamp (40 mU/m2/min insulin infusion) was calculated by tracer dilution techniques (6,6 2H2 glucose tracer continuous infusion) and was significantly lower in hypertensives with microalbuminuria than in those without (H2 versus H1 versus controls: 3.41 +/- 0.51 versus 6.52 +/- 0.62 versus 7.03 +/- 0.48 mg/kg/min; mean +/- SE). Whole-body glucose utilization in NIDDM patients--NIDDM4 versus NIDDM3 versus NIDDM2 versus NIDDM1 versus controls--was: 1.86 +/- 0.31 versus 2.21 +/- 0.39 versus 2.01 +/- 0.40 versus 5.98 +/- 0.77 versus 5.52 +/- 0.92 mg/kg/min (mean +/- SE). Whereas the first three subgroups did not differ among themselves, they had significantly lower glucose utilization than did the normotensive NIDDM1 patients without microalbuminuria and nondiabetic controls (P < 0.01). Hypertensives with microalbuminuria had higher Vmax of sodium-lithium countertransport (Na/Li CTT) in red blood cells than did both hypertensives without microalbuminuria and controls. It was also observed that NIDDM patients with microalbuminuria had higher Vmax of Na/Li CTT than did NIDDM patients without microalbuminuria and controls.(ABSTRACT TRUNCATED AT 250 WORDS)


Normal blood pressure in patients with insulinoma despite hyperinsulinemia and insulin resistance. This article examines the relationship between blood pressure and serum insulin patients with endogenous hyperinsulinemia due to insulinomas. The hypothesis that hyperinsulinemia is an independent causal factor in the development of essential hypertension in this patient population was investigated. Inappropriately high plasma concentrations of insulin and proinsulin were found in these patients; however, their blood pressure levels did not differ from those of normal control subjects. Moreover, the surgical removal of the insulinomas did not reduce their blood pressure. Therefore, these findings argue against the hypothesis that hyperinsulinemia is an independent causal factor in the development of essential hypertension in humans.


Alterations in insulin receptor and substrate phosphorylation in hypertensive rats. Insulin stimulates tyrosine phosphorylation of the insulin receptor and of an endogenous substrate of approximately 185 kd (insulin receptor substrate 1 or IRS-1) in most cell types. Tyrosine phosphorylation of insulin receptor and of IRS-1 have been implicated in insulin signal transmission based on studies with insulin receptor mutants. In the study presented here, the levels and phosphorylation state of the insulin receptor and IRS-1 in liver and muscle after insulin stimulation in vivo have been examined in spontaneously hypertensive rats (SHR) by immunoblotting with antipeptide antibodies to insulin receptor and IRS-1 and antiphosphotyrosine antibodies. It was found that the levels of insulin receptor and IRS-1 protein in liver and muscle are similar in controls (Wistar-Kyoto rats) and SHR. By contrast, there is a decrease in autophosphorylation in the liver and muscle of SHR and a parallel decrease in phosphorylation of IRS-1. These data indicate that reduced insulin receptor kinase activity and reduced substrate phosphorylation may play an important role in the impaired insulin action in the hypertensive rat.


Cellular ions in hypertension, insulin resistance, obesity, and diabetes: a unifying theme. The clinical linkage of hypertensive cardiovascular disease, left ventricular hypertrophy, and accelerated atherosclerosis with a spectrum of metabolic disturbances including peripheral insulin resistance, hyperinsulinemia, obesity, and frank non-insulin dependent diabetes mellitus, has been increasingly appreciated. However, the underlying biologic basis mediating this clinical association remains unclear. Nuclear magnetic resonance techniques have been used to measure various intracellular ion species in human erythrocytes and have found that common, shared intracellular abnormalities of cytosolic free calcium, free magnesium, and pH occur in each of these clinical syndromes. Specifically, essential hypertension is characterized by higher fasting free cytosolic calcium concentrations and reciprocally lower intracellular free magnesium and pH levels compared with those of normotensive control subjects. Furthermore, for all subjects, free calcium and free magnesium levels were closely related both to the left ventricular mass and to the degree of insulin resistance present. Moreover, these same intracellular ionic lesions were found in normotensive obese and/or non-insulin diabetic individuals. Last, evidence has recently been provided that the cardiovascular consequences of increased dietary sugar and salt intake may well be determined by their concurrent influence on cellular ion metabolism. These data led to a hypothesis for a central role for altered cellular ion homeostasis in mediating the clinical linkage of cardiovascular and metabolic disease. According to this ionic hypothesis, essential hypertension, non-insulin dependent diabetes, and their frequently associated features of obesity, left ventricular hypertrophy, and accelerated atherosclerosis all derive from and reflect different clinical manifestations of the same underlying cellular lesion, characterized at least in part by elevated cytosolic free calcium and suppressed free magnesium levels.


Molecular genetic approaches to the identification of genes involved in the development of nephropathy in insulin-dependent diabetes mellitus. Genetic factors contribute significantly to the development of diabetic nephropathy in patients with insulin-dependent diabetes mellitus. This report discusses some models of diabetic nephropathy that incorporate genetic susceptibility and presents strategies for identifying the responsible genes. To identify variation at a locus, newly developed methods are discussed that employ denaturing gradient gel electrophoresis to study sequence differences in both polymerase chain reaction-amplified DNA fragments and genomic DNA. These techniques are illustrated with studies of the angiotensinogen gene and the insulin receptor gene. In preliminary data from a comparison between individuals with and without diabetic nephropathy, no DNA sequence difference in that part of the angiotensinogen gene that codes for angiotensin I was found. However, with a probe corresponding to exons 7 and 8 of the insulin receptor gene and denaturing gradient gel electrophoresis of Rsal digestions of genomic DNA, different distributions of a DNA polymorphism were found in patients with fast as compared with slowly progressing nephropathy. The interpretation of this finding and the need for further studies are discussed. In conclusion, the advent of methods of molecular genetics makes possible studies on genetic determinants of diabetic nephropathy. However, more clinical and epidemiologic data are needed to find out how many genes are involved and how they interact with exposure to diabetes. Foremost, DNA from families with two or more siblings with diabetic nephropathy must be collected to permit the necessary genetic studies.


Does antihypertensive treatment prevent progression of microalbuminuria to overt proteinuria in insulin-dependent diabetic patients? Prospective studies in insulin-dependent diabetic patients have shown that microalbuminuria is a strong predictor of clinical nephropathy. Because this syndrome is associated with a dramatic excess in mortality, different types of intervention have been proposed for insulin-dependent diabetic patients with microalbuminuria to prevent or postpone clinical nephropathy. The effects of antihypertensive treatment are being extensively investigated. Beta-blockers, calcium antagonists, and angiotensin-converting enzyme inhibitors have proved effective in reducing albumin excretion and postponing overt proteinuria in hypertensive and normotensive insulin-dependent diabetic patients with microalbuminuria. However, many problems remain to be solved. A decrease in albumin excretion may not be an adequate endpoint for intervention trials, because it has been shown that patients with normal albumin excretion can develop diabetic nephropathy lesions, whereas patients with microalbuminuria alone may have little or no pathology. The patients included in these trials all had incipient diabetic nephropathy but exhibited different functional, and probably morphological, forms of the disease. For insulin-dependent diabetic patients with microalbuminuria, the real aim of antihypertensive treatment is not to reduce urinary albumin excretion or to prevent its progression but to preserve renal function and to reduce the incidence of premature cardiovascular deaths. To achieve this, we have to improve our knowledge of the natural history of the early pathology of diabetic nephropathy and of the mechanisms of action of antihypertensive treatment. New large-scale intervention trials will have to be designed in which the patients will have to be carefully characterized on the basis of functional and morphological data.(ABSTRACT TRUNCATED AT 250 WORDS)


A controlled clinical trial of angiotensin-converting enzyme inhibition in type I diabetic nephropathy: study design and patient characteristics. The Collaborative Study Group. A placebo-controlled, double-blind clinical trial has been initiated to determine whether angiotensin-converting enzyme inhibitor (ACEI) therapy with captopril (25 mg three times daily) slows the progressive loss of renal function in patients with type 1 diabetes mellitus. Entry criteria include; (1) ages 18 to 50 yr; (2) onset of insulin-dependent diabetes before the age of 30 yr, insulin dependent for at least 7 yr; (3) 24-h urine protein excretion > 500 mg, plus: (a) diabetic retinopathy or (b) if no retinopathy, a renal biopsy diagnosis of diabetic nephropathy; (4) serum creatinine (SCr) < 2.5 mg/dL; (5) informed consent. Patients follow strict medical management protocols. Systemic blood pressure is controlled to predefined goals (< 140-90 mm Hg). The primary outcome of the Study is a doubling of the patients' entry SCr to at least 2 mg/dL confirmed by a > 50% decrease in GFR by radioactive iothalamate clearance technique. Baseline characteristics of the cohort at entry into the Study are (mean +/- SD): male/female, 52%/48%; age, 35 +/- 8 yr; duration of diabetes, 21 +/- 7 yr; duration of proteinuria, 2.8 +/- 3.3 yr; duration of retinopathy, 4.5 +/- 4.1 yr; 50% of cohort presented with hypertension, duration, 4 +/- 4.7 yr; blood pressure, 139/86 +/- 19/12; SCr, 1.35 +/- 0.44 mg/dL; GFR 78 +/- 32 mL/min; BUN, 24 +/- 11 mg/dL; proteinuria, 3.1 +/- 3.3 g/day; cholesterol, 236 +/- 50 mg/dL; total glycosylated hemoglobin, 11.1 +/- 2.1%.(ABSTRACT TRUNCATED AT 250 WORDS)


[Cancer of the gastric stump].

[Cancer of the gastric stump]. 627 cases of gastric cancer treated surgically during the last 5 years, at the Hospital Nacional "Edgardo Rebagliati Martins" from Instituto Peruano de Seguridad Social (Lima-Perú) were revised. 4 of the patients had been operated before of hemigastrectomy or antrectomy with pyloroplasty for peptic ulcer. The time between the first operation and diagnosis of cancer of the gastric stump was more than 20 years. 3 of these cases were able to be resected. The international incidence of cancer in the gastric stump is 1.1% to 9.2% according to different authors. The risk is higher after 15 years. In the pathogenesis are advocated the lower gastric acidity, biliary reflux, the presence of bacteria, the formation of nitrosamines, intestinal metaplasia, etc. Is necessary to perform periodic endoscopic survey in patients who were treated surgically of peptic ulcer with antrectomy or hemigastrectomy with more than 15 years of evolution.


[Polyps of the colon and the rectum].

[Polyps of the colon and the rectum]. This is a retrospective study en 189 cases of colorectal polyps, from 1985-1989 including medical record review, pathologic diagnosis and surgical management. The main symptom was rectal bleeding. The follow up period and it's relation to colorectal cancer was evaluated, considering this entity as a premalignant lesion. 189 histopathology slides were reclassified according to the actual classification. Males were predominant (69%), with increasing incidence from the fifth decade (62% of the total); a 2% malignization rate was found.


[New epidemic outbreak of cholera in Lima]. We report a new outbreak of cholera on the beginning of last Summer (Dec. 91 and Jan 92). Were 281 patients, 63% male and 36% female, treated in our Cholera Unit of treatment; all of them coming from marginal-urban populations. There was a rate of lethality of inpatients of 0.46% and a mortality of 0.25% over the total of patients that we saw in our hospital; on this summer the outbreak is early and greatest than the summer of 1991. We can conclude that because of epidemic behavior during the whole 1991 and in the time elapsed of 1992, Peru has become an endemic zone of this new disease, while the current epidemiologic settings stay unchanged.


[Redefining dyspepsia].

[Redefining dyspepsia]. On the last years there is a discussion about the dyspepsia for its prevalence and because the symptoms could indicate a serious disease. Now, there are problems with the terminology; functional or organic aspects; it is named non-ulcer dyspepsia or ulcer-dyspepsia; also with the diagnosis and management. This paper is a review about the definition and etiology of dyspepsia.


[Early prognostic risk factors in acute pancreatitis: study of a representative population from Peru]. Thirty-one patients with acute pancreatitis were prospectively evaluated using the Early Prognostic Risk Factors of Ranson and Bank & Wise, in order to assess severity of that condition. The purpose was to determine the usefulness of such factors as clues to orient diagnosis and treatment of acute pancreatitis, particularly in the most severe clinical forms; and the factibility of using them in our setting. The presence of 4 or more of Ranson's and/or 1 or more of Bank & Wise Factors fulfilling positive criteria, identified the patients with a high risk of complications and mortality. Hypocalcemia, leucocytosis and hyperuricemia were the most frequent findings in this group. The development of Early Objective Prognostic Risk Factors in acute pancreatitis, as a clinical concept, has improved the management of these patients. It allows to establish diagnosis and therapeutics upon objective basis.


Small GTP-binding proteins as compartmental markers. Each intracellular compartment involved in the biosynthetic/secretory pathway of eukaryotic cells bears at its surface at least one small GTP-binding protein. Most of them belong to a distinct branch of the p21ras superfamily, the Sec4/Ypt1/rab family. Other proteins are members of the ARF family. They play a key role in the regulation of budding and targeting/fusion events occurring during protein transport.


Beauty and the yeast: compartmental organization of the secretory pathway. Our perception of intracellular organelles and cellular architecture was initially based on striking light and electron micrographs of animal and plant cells. The high degree of compartmental organization within specialized mammalian secretory cells aided early efforts to track the movement of proteins through the organelles of the secretory pathway. In contrast, the morphological detail of the yeast Saccharomyces cerevisiae appeared superficially simple, even primitive, by comparison with the higher eukaryotic cells. However, the combination of genetic tools and the development of assays reconstituting vesicular traffic in yeast have facilitated the identification and characterization of individual proteins that function in the secretory pathway. Analogies between the function of yeast and mammalian proteins in vesicular traffic are being drawn with increasing frequency. In this review, the combination of genetic, biochemical, molecular and cell biological approaches used to study compartmental organization in the yeast secretory pathway will be discussed. The rapid progress in our understanding of yeast membrane traffic has revealed the beauty of working with this organism.


Subcompartments of the endoplasmic reticulum. The endoplasmic reticulum (ER) is the largest continuous endomembrane structure in the cytoplasm. It may be viewed as a series of unique subcompartments. In this review, we examine the rough ER, nuclear envelope and several smooth ER subcompartments. Consideration is given to the characteristic properties and functions of the ER and its domains, and to the formation and maintenance of subcompartments. Associations within the ER membrane bilayer, and with constituents of the cytoplasm and the ER lumen, contribute to the formation of domains and lead to the establishment of subcompartments that reflect specialized functions and vary according to the physiologic state and phenotype of the individual cell. Although the structural complexity of some ER subcompartments (such as the sarcoplasmic reticulum) is highly elaborate, the ER remains a dynamic organelle, subject to assembly and disassembly, capable of extensive remodelling and active in exchange with other organelles through mechanisms of membrane transport.


Biogenesis of secretory granules.

Biogenesis of secretory granules. The biogenesis of secretory granules in endocrine, neuroendocrine, and exocrine cells is thought to involve a selective aggregation of the regulated secretory proteins into a dense-cored structure. The dense-core is then enveloped by membrane in the trans-Golgi network and buds, forming an immature secretory granule. The immature secretory granule then undergoes a maturation process which gives rise to the mature secretory granule. The recent data on the processes of aggregation, budding and maturation are summarized here. In addition, the current knowledge about the mature secretory granule is reviewed with emphasis on the biogenesis of the membrane of this organelle.


Pathways of protein sorting and membrane traffic between the rough endoplasmic reticulum and the Golgi complex. Recent results have provided increasing evidence for the existence of an intermediate membrane compartment between the rough endoplasmic reticulum and the Golgi complex which seems to function in protein sorting and the regulation of membrane traffic in the early part of the exocytic pathway. Localization of resident marker proteins has shown that this compartment consists of both peripheral and central elements. The aim of the present review is to combine the data on the pre-Golgi compartment with previous ideas of membrane traffic at the ER-Golgi interface. We propose a model which describes how mobile, endosome-like elements of the pre-Golgi compartment function in the generation of the compositional and functional boundary between the widely distributed ER and the more centrally located Golgi stacks.


Genital herpes and prevention of HIV infection: the report of a study in progress. Although genital herpes is not a reportable disease, research has shown that about one in five women and one in eight men carry the antibody. The chronic ulcerative disease may place affected individuals at risk for human immunodeficiency virus (HIV) infection. This article directs attention to a study-in-progress of adaptation in young adults with genital herpes. The use of qualitative and quantitative approaches in the study of adaptation will increase knowledge of adaptation regarding both process and outcome.


[Oral magnetic particles as an MR contrast medium for the gastrointestinal tract]. The authors summarise their experience of four clinical studies with a negative oral contrast agent for magnetic resonance imaging of the abdomen and pelvis. 140 patients were enrolled in the studies. These were partly comparative studies pre- and post-contrast, partly at 0.5 and 1.5 T, partly pre-injection and post-injection of glucagon. All patients received 800 ml of a suspension of oral magnetic particles "OMP". The distribution of this contrast agent was homogeneous throughout the entire GI tract. A complete or partial signal void was observed in all patients in T1, T2-, and intermediately weighted images. Generally, diagnostic information was higher after contrast. Artifacts caused by peristalsis and movement of the diaphragm were fewer after contrast. After contrast metallic artifacts were observed in a minority of patients. Adverse events after contrast were minimal; they included nausea and vomiting.


Healthcare needs scale for patients with HIV/AIDS: content validation. The authors of this study adapted Peters' (1987) community health specifications of patients' nursing requirements so they could be applied to patients with HIV/AIDS in hospital, dedicated outpatient HIV clinic, home care, and long-term care settings. The authors then collected validity evidence on the revised specifications, developed a sample of 62 multiple-choice items, and obtained content-related validity evidence via a judgmental review panel. The results produced: (a) a set of specifications for the environmental, psychosocial, physiological, and health behaviors domains; and (b) a 44-item scale of patient characteristics related to four levels of healthcare needs.


[Manganese DPDP as a contrast medium for MR tomography of focal liver lesions. Tolerance and image quality in 20 patients]. Twenty patients with focal liver lesions (18 metastases, 1 hepatocellular carcinoma, 1 cholangiocarcinoma) were given manganese DPDP as part of a multicentric phase II study of paramagnetic hepatobiliary MR contrast media. 5 mumol/kg manganese DPDP were injected into 10 patients in a concentration of 50 mumol/ml or 10 mumol/ml (3 ml/min). Blood pressure, pulse rate, ECG, respiratory rate, body temperature, blood and serum parameters and the patients' subjective feelings were recorded. MRI was performed with 1.5 T using T1- and T2-weighted sequences. 6 patients reported 8 side effects (flushing, feeling of warmth, metallic taste); 7 of these were produced by the 50 mumol concentration. Two hours after injection there was a significant reduction in alkaline phosphatase which was no longer present after 24 hours. On T1-weighted images manganese DPDP resulted in marked improvement in the contrast difference between the lesions and the liver parenchyma which resulted in a marked increase in the signal to noise ratio. Comparing the two concentrations, better results were obtained by the lower concentration. Extrahepatic uptake was found in the gallbladder, duodenum, pancreas, kidneys, gastric mucosa and myocardium. Manganese DPDP in a concentration of 10 mumol/ml and a dose of 5 mumol/kg is a well tolerated contrast medium which improves the demonstration of focal liver lesions in view of its distribution and uptake. The mechanisms for the transitory side effects require further studies.


[The value of tumor volumetry as opposed to bidimensional determination of tumor size during follow-up of hepatic metastases from colorectal carcinoma]. 36 patients with liver metastases due to colorectal carcinoma under treatment with arterial perfusion chemotherapy of the liver with 5-fluoro-2-desoxyuridine (FUDR) via a subcutaneous pump were investigated by axial liver CT at 6-monthly intervals. In all examinations a dynamic CT scan with intravenous bolus injection of contrast medium was carried out following a native scan. Changes in tumour size were documented by means of 1. volumetry and 2. bidimensional measurement according to WHO criteria. Since we were not able to assess small newly developing lesions within the liver using the volumetric classification, the WHO-classification showed much higher sensitivity in cases of progressive disease. In addition, volumetric determination of tumour size by means of region-of-interest technique proved to be rather impracticable in clinical routine compared to bidimensional measurement.


[The place of portangiography in the follow-up control of locoregional chemotherapy]. 101 portangiographies in patients with liver metastases from colorectal primaries who underwent hepatic intraarterial or intraperitoneal chemotherapy were performed and studied between January 1991 and February 1992. 81% of the examinations did not involve complications. In 19% of the angiographies abnormalities of the arterial perfusion of the liver, like occlusion, dissection or narrowing of hepatic arteries, were found. We conclude that portangiography is a very important investigation before regional chemotherapy.


[Magnetic resonance tomographic imaging of pulsatile CSF movement in communicating hydrocephalus before and after shunt placement]. 16 patients with hydrocephalus communicans and 5 healthy volunteers were examined to demonstrate the pattern of the pulsatile CSF flow. After implantation of a CSF shunt system the same patients were examined again to show the influence of the shunt on the CSF pulsations. We used a flow-sensitised, cardiac-gated 2D FLASH sequence and analysed the phase and magnitude images. It could be shown that most patients (n = 12) had a hyperdynamic pulsatile flow preoperatively. After shunt implantation the pulsatile CSF motion and the clinical symptoms were improved in 8 of these patients. MRI of pulsatile CSF flow movement seems to be a helpful noninvasive tool to estimate the prognosis of a shunt implantation in patients with hydrocephalus communicans.


[Sonographic findings in lateral ligament lesions of the upper ankle joint following conservative and operative therapy]. 72 patients with injury of the ankle joint were examined with ultrasound after therapy. Sonographic findings were assessed by plain x-ray films and stress views. In 39 patients an injury of the lateral ligament was treated by surgery and in 33 patients without surgery. 40 patients showed a scar of the lateral ligaments. Patients treated without surgery and showing a scar in ultrasound demonstrated a smaller tilt of the talus in stress views than patients without scars. Measurement of stability was not possible. In conclusion, sonography is a valuable tool in examining the ankle joint after therapy. With regard to stability, stress films cannot be replaced by sonography.


Case management problems and home care.

Case management problems and home care. The author summarizes a review of the case management problems encountered at the Visiting Nurse Service of New York, the largest certified provider of home care services to people with AIDS in the world. Case management problems can be divided into four general categories: client/significant others, housing/community, support services, and nurses' needs. Concrete solutions to these problems are discussed. As the number of people with AIDS increases, more home care agencies and discharge planners will need to consider these issues when planning care in the community.


[Clinical potentialities and limitations of two- and three-dimensional time-of-flight MR angiography in the diagnosis of carotid stenosis]. For diagnosing a carotid artery stenosis, 26 patients underwent MR angiography. A spin echo (SE) sequence with presaturation on which the flowing blood appears with low signal intensity was applied, as well as a two- and three-dimensional gradient echo (GRE) sequence with flow compensation, showing blood flow with high signal intensity. Subsequently, projection angiograms were made from the MR images with a maximum intensity projection algorithm. Degree, length and localisation of a carotid artery stenosis were reviewed. To find out the clinical usability, the results of the MR angiograms were compared subsequently with the findings of intravenous digital subtraction angiography (i.v. DSA). In comparison with DSA a correlation in the degree of stenosis was noticed in 42 out of 48 SE-, in 39 out of 52 2-D GRE and in 41 out of 48 3-D GRE sequence angiograms. The length of 34 moderate and severe stenoses, demonstrated by DSA, was overestimated 5 times with the SE-sequence, 9 times with the 3-D and 23 times with the 2-D GRE sequence. MR angiography with a 3-D GRE sequence is suitable for screening for carotid artery stenosis. In cases of severe stenosis an SE sequence should be performed for more precise delineation of the stenotic lesion.


Educational learning needs of ANAC members--1991. One of the purposes of the Education Committee of ANAC is to assess the learning needs of ANAC members. In order to achieve this purpose the Educational Needs Assessment tool was developed. It was included in the July 1991 issue of ANACDOTES and sent to the 1,116 members of ANAC. One hundred and fifty-five ANAC members responded (14%) by the cut-off date of August 15th. Demographic information about the respondents was compared to demographic data about ANAC members; the top three interest and expertise areas in the primary, secondary, tertiary prevention of HIV infection categories were identified. The Educational Needs Assessment tool can be used in other settings to plan programs and identify learning needs.


[Doppler and duplex sonography of the vertebral arteries]. In a prospective study 451 patients were examined with extracranial CW-Doppler sonography (mastoidal slope), suboccipital transcranial Doppler sonography and colour-coded duplex sonography to evaluate unusual vertebral arteries (hypoplasia, stenosis and occlusion). Colour duplex sonography was used as reference method. CW-Doppler sonography had a sensitivity of 100% and a specificity of 27% for the detection of an unusual vertebral artery. For transcranial Doppler sonography these values are 38% and 58%. Our study showed that CW-Doppler is a useful screening examination for identifying pathological findings of vertebral arteries. In case of abnormalities in CW-Doppler, duplex sonography, especially colour-coded duplex sonography, should be added.


[Angiographic diagnosis in giant cell arteritis of the arm arteries]. Three women of 66, 68 and 69 years of age presented with chronic arm claudication caused by giant cell arteritic stenoses and occlusions of their arm arteries. In the early stage of the disease, arteriography revealed smooth or undulatory long-segment narrowings. Subsequently, spindle-shaped filiform stenoses developed. They were unilateral in one patient, bilateral-symmetric in another and like a string of beads in the third. In the end, untreated arteritis resulted in smoothly tapered occlusions of the diseased vessels. In patients with symptoms and signs suggestive of giant cell arteritis, typical arteriographic findings may confirm the diagnosis even if histopathological proof is lacking.


[Magnetic resonance angiography of the renal veins and the vena cava inferior for the staging of renal cell carcinoma]. The staging of renal cell carcinoma (RCC) comprises exclusion of tumour expansion into the renal veins and the inferior vena cava (IVC). In 44 patients with RCC these vessels were examined using MRA on the basis of "time-of-flight" technique (coronal/axial 2D GE-flash-sequence, MIP-algorithm). The method was evaluated against contrast-enhanced CT and DSA in normal conditions and tumour-involved IVC (n = 12) and renal veins (n = 32) respectively. Following analysis of projection-angiograms (PA) and individual slices the results of MRA without contrast material included an information on vascular tumour extension that was identically safe as CT and DSA. In coronal slice orientation tumour extension into the vena cava was proven in 100%, and into the renal veins in 84%. Additional axial slices were necessary to demonstrate tumour extension into the renal veins in unclear cases. Single slices showed to be superior to PA for a correct identification of the size of the tumour thrombus.


[Stent-supported percutaneous therapy of iliac vein stenosis following operative thrombectomy and placement of a shunt]. Among 15 patients with acute thrombotic disease of pelvic veins who had been submitted to operative thrombectomy and creation of arteriovenous fistula in the groin, 12 presented with stenotic lesions 3 months later. These stenoses were submitted to percutaneous angioplasty. If angioplasty failed, percutaneous placement of a vascular stent (wall stent) was performed immediately (n = 7). Stenting in cross-over-technique proved practicable in all cases. Secondary stenotic disease in the exclusively dilated area was observed in 3/5 cases and was also treated with a wall stent. In one patient with recurrent stenoses who refused stenting, extended thrombosis occurred after occlusion of the AV-fistula. At mid-term PTA was successful in only two cases. Intimal hyperplasia was observed in only one wall stent treated patient. Percutaneous treatment of iliacal stenoses in patients with postthrombotic syndrome may be performed safely under the protective effect of the fistula. With the presented technique, patency of pelvic veins could be restored in 11/12 patients with postoperative significant venous stenoses.