[Ethnomedical and transcultural psychiatric aspects of migration]. In consideration of the current socioeconomical and political development in the world a dramatic increase of migration streams are expected. Migrant families are always a new phenomenon on both sides in host countries. One important root of these specific problems are: Culture-conditioned differences concerning value orientation between immigrants of several ethnics on one hand and the resident population on the other hand, but also among the immigrants of several ethnic groups themselves. These differences of the value orientation, of course, also refer to the illness concepts, the illness behavior as well as utilization of assistance among the several sectors of the Health Care Systems. It is expected that the professional sector of the Health Care Systems in the host countries will be confronted massively with ethnomedical and transcultural-psychiatric aspects of migration in the future. An adequate medical care of the migrants (especially concerning psychiatric disorders) will only be possible in case of an appropriate consideration of such culture-bound peculiarities.


[Psychosocial stress factors in the historical transition]. More and often in our consultations we have seen that parents as well as children and adolescents attribute psychosomatic disorders and learning and behavioural disturbances to altered conditions caused by political changes. Interrogating 277 pupils of the 7th to 11th class in the combined Junior/Senior High School of Erfurt, we wanted to answer the question, to what extent changes caused by the new era have influenced the emotional stress loads of average adolescents. It could be concluded that two thirds of the pupils questioned can compensate very well for the stress situations that are associated to social reforms. However about one third of the children and adolescents are strongly stressed and have developed learning problems, behaviour problems and/or psychosomatic disorders. Most stress factors manifest in the family situation. The disconcertion of parents and the associated deterioration of the family's emotional atmosphere were stated as the essential factors.


[Manifestation of psychiatric disorders caused by stress factors of the historical transition in former East Germany]. We analysed the case histories of 149 patients who had been given hospital treatment for psychic disorders. Among them we found nine patients (6%) with stress factors caused by the radical historical upheavals in the former GDR, which had played a main role in the pathogenesis of the psychic disorders. In these cases it was above all stress factors which indirectly affected the child through the family situation.


[Transcultural problems of child and adolescent psychiatry or sequelae of inverse migration? On diagnosis and treatment of children and adolescents of former East Germany in West Germany of the past]. Against a background discussion whether there has been a different cultural development within the two former German states, the question is raised, whether this possible difference could lead to different influences on psychiatric illness among children and adolescents. Problems in ethnological research in general together with problems found within cross cultural psychiatry are discussed. A study of a group of 19 children and adolescents, presenting at a psychiatric clinic with the historically significant if not seldom experience of inverse migration is described. From this population only n = 4 children appeared to be significantly affected by their new surroundings. It is proposed that further investigations is needed to ascertain whether the experience of inverse migration does indeed constitute a psychological stress for children and adolescents from the former GDR.


[Some impressions of child and adolescent psychiatric management in Berlin after the fall of the wall]. The fall of the Berlin wall caused a sudden increase in migration from East-Germany to West-Berlin. In our sample we compared 155 Berlin elementary school children to 17 children from East-Germany now living in Berlin and 25 immigrant children most oft them coming from Turkey and Poland. Although many authors expected short-term disorders of adaptation, we found a constancy of psychiatric diagnosis in the migration group. We noticed important differences particularly in the new psychosocial situation of the former East German mothers, with many single-mother-families, where the mothers now were often unemployed.


[Inpatient and partial hospitalization facilities for child and adolescent psychiatry in the unified Germany, 1991]. First results of the project "Surveys regarding the structure of psychiatric institutions for children and adolescents in the Federal Republic of Germany" are described. On July 1, 1991 there were 111 in-patient institutions with a total capacity for 6363 children and youths. The contributing shares of each state (Bundesland) vary enormously. The number of accommodations per 100,000 residents is between 2.1 and 19. One reason for this discrepancy lies in the fact that the services of the institutions are called upon without regard to the state borders. More important though is the fact that in the new states the psychiatric institutions for children and youths also treat young patients who are psychologically or mentally handicapped with neuropsychiatric complications to a greater extent than comparable institutions in the old states.


Trisomy 16 confined to the placenta.

Trisomy 16 confined to the placenta. Two cases with trisomy 16 confined to the placenta are presented. Prenatal diagnosis was indicated because of fetal growth retardation. In case 1, a phenotypically normal but small-for-date boy was born. In case 2, the fetus turned out to be triploid on cordocentesis. In both instances the trisomy 16 was recovered from the placenta. Recovery indicates that the abnormality was present in the placenta during the time of fetal growth retardation, which supports an aetiological relationship. Strict appliance of the current models cannot readily explain the observed discrepancies. In case 2, a chimeric placenta as a result of a vanishing twin is assumed. Cases of placental trisomy 16 published after 1988 are reviewed. It is concluded that confined placental trisomy 16 can cause intrauterine growth retardation if present in both the direct preparation and the villus culture. The chances of finding a chromosomally abnormal fetus (mosaic trisomy 16, triploidy) after diagnosis of trisomy 16 in chorionic villi are low but warrant further investigations.


The outcome of pregnancy and prenatal chromosomal diagnosis of fetuses in couples including a translocation carrier. In order to evaluate the relation between chromosomal translocation and the outcome of pregnancy, 50 couples were examined. Subjects consisted of 35 couples that included a reciprocal translocation carrier; 13 included a Robertsonian translocation carrier and 2 included a carrier of a mosaic reciprocal translocation. The reasons for performing chromosomal examinations were mainly infertility and abnormality of neonates. The rates of miscarriages and neonatal abnormalities in prior pregnancies were significantly higher than the birth rate of morphologically normal newborns. The presence of a translocation is closely related to reproductive failure because of the chromosomal imbalance. However, prenatal chromosomal examination after the 15th gestational week in subsequent pregnancies revealed that almost half of the fetuses showed normal karyotypes and only 12.8 per cent of the fetuses showed a chromosomal imbalance. Many chromosomally imbalanced fetuses are spontaneously aborted before amniocentesis. The risk of chromosomal imbalance is relatively low in prenatal diagnosis, but partial trisomies of small rearrangements tend to be preserved.


Fetal presentation of Morquio disease type A. A fetus with mucopolysaccharidosis type IV A (Morquio type A) is described. The family had one affected child exhibiting symptoms of classical Morquio A disease, and late in the subsequent pregnancy prenatal diagnosis was requested. At 23 weeks' gestation, moderate ascites was detected by detailed ultrasound scan and keratan sulphate was found in the amniotic fluid. The pregnancy was terminated by prostaglandin induction and the diagnosis of mucopolysaccharidosis type IV A was confirmed by demonstration of a deficiency of N-acetylgalactosamine-6-sulphate (GalNac-6-S) sulphatase in cultured amniotic cells and in post-mortem fibroblast cultures. The activities of beta-galactosidase and arylsulphatase A were normal, ruling out Morquio disease type B and multiple sulphatase deficiency. These results indicate that mucopolysaccharidosis IV A (a disease that predominantly affects the skeletal system) may produce ascites in the fetus to such an extent that it can be detected by ultrasound.


Reproductive behaviour and prenatal diagnosis following genetic termination of pregnancy in women of advanced maternal age. One hundred and fifty-one women of advanced maternal age who underwent genetic termination of pregnancy (TOP) were studied for their reproductive behaviour and the type of procedure for prenatal diagnosis in a subsequent pregnancy. A total of 59 women (39 per cent) had a further pregnancy. In all continuing pregnancies prenatal diagnosis was performed, of which 75 per cent consisted of chorionic villus sampling (CVS). Reproductive behaviour following a genetic termination was negatively correlated with maternal age and parity. Both reproductive behaviour and the choice to undergo a diagnostic procedure in the next pregnancy were independent of the type of diagnostic procedure in the previous affected pregnancy.


Mucolipidosis type IV: accumulation of phospholipids and gangliosides in cultured amniotic cells. A tool for prenatal diagnosis. Cultured amniotic fluid cells from two mucolipidosis type IV (MLIV)-affected fetuses demonstrated accumulation of phospholipids and gangliosides when compared with normal controls. Like cultured skin fibroblasts from MLIV patients, cultured amniotic cells from the affected fetuses accumulated primarily lyso phospholipids and this could be demonstrated by radioactive labelling with appropriate precursors, either inorganic phosphate or oleic acid. Furthermore, like cultured skin fibroblasts, there was significant retention of exogenously supplied GD1A ganglioside in the affected amniotic cells. This storage was previously demonstrated to be unique to MLIV and thus can be used at present as a specific procedure for prenatal diagnosis of MLIV.


Prenatal diagnosis of distal arthrogryposis type I by ultrasonography. Two consecutive pregnancies in a woman with initially undiagnosed type I distal arthrogryposis (DA) are reported. A prenatal diagnosis of the condition was made by ultrasound in the 17th week of gestation in one of the pregnancies, whereas in the subsequent pregnancy the disorder was excluded as early as 13 weeks' gestation. The diagnoses were verified at birth. The feasibility of prenatal diagnosis of DA type I in the second trimester is thus confirmed and its possibility in the late first trimester is suggested.


Prenatal diagnosis of Huntington's disease (HD): experiences with six cases and PCR. In the course of a 2-year predictive testing programme for Huntington's disease (HD), six couples from a total of 52 applicants requested prenatal testing. In each case, the pregnancy was in the first or second trimester when the couples were referred for DNA diagnosis. In five cases, exclusion testing was offered; in one case, a person at risk with an increased risk of being a gene carrier requested prenatal diagnosis. In all cases, informative markers for prenatal testing could be determined. Whenever possible, the newer technique of polymerase chain reaction (PCR) for D4S125 was applied to perform rapid prenatal diagnosis. Two couples withdrew before chorionic villus sampling was undertaken; prenatal diagnosis was completed in the remaining four cases. After exclusion testing, two pregnancies were determined to have an increased risk and two fetuses to have a low risk of being HD gene carriers.


Second-trimester cancer antigen 125 and Down's syndrome. This study explores if assay of cancer antigen 125 (CA 125) in maternal serum might aid the detection of Down's syndrome in the second trimester of pregnancy. CA 125 levels were determined retrospectively in stored maternal serum samples from ten Down's syndrome pregnancies and 78 controls matched for gestational and maternal age. In addition, second-trimester amniotic fluid samples from nine Down's syndrome and 109 unaffected pregnancies were analysed for CA 125. Maternal serum CA 125 values for Down's syndrome pregnancies were lower, with the median being 0.72 multiples of the unaffected population median. The medians for affected and unaffected pregnancies did not differ significantly and there was a considerable overlap in the range of values of cases and controls. The distribution of amniotic fluid CA 125 levels for Down's syndrome pregnancies resembled that for controls. From our present results, we could not find an association between Down's syndrome and second-trimester maternal serum or amniotic fluid CA 125 levels.


Prenatal detection of multiple copies of a familial supernumerary marker chromosome. Direct preparations and long-term cultures from a chorion villus biopsy, taken because of a known maternal additional marker chromosome, showed a 48,XX,+mar,+mar karyotype in all cells examined. The same karyotype was revealed in a subsequent amniotic fluid sample and in cord blood at delivery. Detailed examination of the child at delivery and at 1 year of age showed no evidence of phenotypic abnormality or developmental problems.


Prenatal diagnosis of tetrasomy 12p by in situ hybridization: varying levels of mosaicism in different fetal tissues. Prenatal diagnosis of tetrasomy 12p is complicated by the discrimination of the 12p isochromosome from the duplication 21q as well as the level of mosaicism demonstrated in the particular tissue sampled. In this disease, a high percentage of chromosomally abnormal cells are generally found in fibroblastic cells, but lymphocyte karyotypes from the same individual may be normal. We report on the pregnancy of a 37-year-old female who presented to our centre at 16 weeks' gestation for genetic amniocentesis. Sonography of the fetus revealed dextrocardia and diaphragmatic hernia. Chromosome analysis of amniocytes demonstrated mosaicism of a 47,XY,+i(12p) line in 80 per cent of cells and a normal male line (20 per cent), consistent with the Pallister-Killian syndrome. Following termination, a 220 g male fetus of 18 weeks was examined. A flattened nose and low-set ears were noted. In situ hybridization with a chromosome 12 centromeric probe in lymphocytes and skin cells unequivocally confirmed the karyotype and showed the presence of a single centromere in the abnormal chromosome, suggesting a true isochromosome. Chromosome analysis of various fetal tissues was performed and the following percentages of abnormal cells were found: skin 100 per cent, chorion 50 per cent, placenta 30 per cent, and blood 80 per cent. The high frequency of tetrasomic cells in fetal blood at this early gestational age is noteworthy, since most reports of this syndrome show a very low percentage of abnormal cells postnatally.


Prenatal diagnosis of Pallister-Killian syndrome: resolution of cytogenetic ambiguity by use of fluorescent in situ hybridization. We report a case of Pallister-Killian syndrome initially diagnosed prenatally as tetrasomy 21. A 33-year-old primiparous woman was noted at 24 weeks' gestation to have moderate polyhydramnios. Ultrasonography showed diminished fetal stomach filling, hydronephrosis, and prominence of the cisterna magna. Cytogenetic analysis of cultured amniocytes was initially interpreted as mosaic tetrasomy 21: 46,XX/47,XX,+i(21q). The patient was then referred to our centre for genetic counselling. At 34 weeks' gestation, a dysmorphic infant was delivered and died within 30 min. Physical features were consistent with the Pallister-Killian syndrome. Renal, gastrointestinal, and central nervous system anomalies were found at post-mortem examination. Analysis of peripheral lymphocytes revealed 5 per cent of cells with a marker chromosome, while 92 per cent of cultured fibroblasts had this same marker. Fluorescent in situ hybridization (FISH) using an alpha-satellite probe for chromosomes 13 and 21 failed to hybridize to the marker, while a chromosome 12 centromeric probe unequivocally identified it as an i(12p). Use of FISH can provide rapid, specific prenatal diagnosis of ambiguous marker chromosomes and improve prenatal counselling.


Fetal granulocytes in maternal venous blood detected by in situ hybridization. Fetal male cells from maternal venous blood were detected by a non-radioactive in situ hybridization method using the biotinylated Y-specific DNA probe pY431. The hybridizations were performed on Ficoll-Paque-isolated nucleated blood cells obtained from 11 pregnant women in the seventh to 31st week of gestation. A Y-specific signal was detected in both granulocytes and lymphocyte-like cells in seven of the 11 women studied. These women gave birth to boys. In one of the four remaining cases, a Y-specific signal was detected in the lymphocyte-like cells but not in the granulocytes. This woman gave birth to a girl. The other three women had no cells with a Y-specific signal and all three gave birth to girls. Altogether, 83,500 nucleated cells were analysed. One hundred and three cells showed a Y-specific signal. Of these Y-specific cells, 62 per cent were granulocytes and 38 per cent lymphocyte-like cells. Our results suggest that fetomaternal transfer of granulocytes is common and that it occurs as early as in the seventh week of gestation. None of the ten non-pregnant female control samples showed positive cells with the Y-chromosome-specific probe; approximately 97 per cent of the cells from the five adult male controls showed a Y-specific signal. Our results indicate that in situ hybridization using a Y-specific DNA probe performed on granulocytes in maternal blood can be used for fetal male sex determination.


Preparation of ferric adsorbent paper and its interaction with phosphate-containing biomolecules. A procedure for the synthesis of a selective adsorbent for phosphate-containing biomolecules is described. The sorbent is based on Whatman chromatography paper, which is activated with epichlorohydrine, followed by the coupling of iminodiacetic acid to the active surface of the sorbent. The immobilized complex-forming chelating groups are saturated with ferric ions. The synthesized adsorbent is a counterpart to Chelating Sepharose and makes it possible to extend the use of immobilized ferric chelating groups for analytical purposes. It displays a high affinity towards compounds containing free terminal phosphate groups (phosphopeptides, nucleotides). The results of the binding experiments are compared to the corresponding data obtained with Chelating Sepharose gels.


Purification of the neurite outgrowth promoting fragment of mouse laminin. A method for isolation of the neurite outgrowth promoting fragment of mouse laminin (fragment 8) is described in this paper. Besides producing excellent yields, this method was shown to be fast and practical, since it is based on a single step which consists in an ion exchange chromatography of elastase digested laminin.


Hydration of amino acid side chains: dependence on secondary structure. Energy calculations have been used to study the hydration sites around the polar groups of serine, threonine and tyrosine side chains. These hydration sites depend not only on the hybridization of the polar group but also on the local secondary structure, the chi 1 side chain torsion angle and the position of the hydroxyl hydrogen atom. For tyrosine side chains, two solvent sites are found approximately in the plane of the ring. Even for serine and threonine side chains only two minimum energy sites are found in general of which one is in an expected position within hydrogen bonding of the hydroxyl hydrogen atom (unless this is blocked from interaction with solvent molecules by, for example, Oi-4 or Oi-3. The position of the second of these sites depends not only on the position of the hydroxyl oxygen but also on neighbouring main chain atoms to which it can also hydrogen bond. There is good agreement with the solvent distributions obtained from crystallographic data.


Purification of rat urinary kallikrein: comparative studies with rat submandibular gland kallikrein-like serine protease. A 427-fold purification of rat urinary kallikrein (RUK) was achieved in three steps involving chromatography on columns of DEAE-Sepharose CL-6B, gel filtration on Sephadex G-100 and affinity chromatography on a column of benzamidine-Sepharose. Purified enzyme showed a single band on SDS-PAGE with an estimated molecular weight of 43,000. The amino-terminal sequences of the first 25 residues of RUK resemble the reported sequence for true kallikrein and share 80% identity with rat submandibular gland (RSMG) kallikrein-like serine protease. The RUK is highly reactive towards kallikrein substrates Bz-pro-phe-arg-pNA and DL-val-leu-arg-pNA, and plasmin substrate D-val-leu-lys-pNA. RSMG enzyme is more reactive towards Bz-val-gly-arg-pNA and tosyl-gly-pro-arg-pNA, preferential chromogenic substrates for trypsin-like proteases and thrombin, respectively. Both leupeptin and aprotinin inhibit RUK strongly, but soy bean trypsin inhibitor has no effect on this enzyme. RSMG enzyme is poorly inhibited by any of these inhibitors. The data suggest that although both enzymes are members of tissue kallikrein multigene family, urinary enzyme is a true kallikrein and RSMG enzyme is a kallikrein-like serine protease with different substrate specificity.


Quantile distributions of amino acid usage in protein classes. A comparative study of the compositional properties of various protein sets from both cellular and viral organisms is presented. Invariants and contrasts of amino acid usages have been discerned for different protein function classes and for different species using robust statistical methods based on quantile distributions and stochastic ordering relationships. In addition, a quantitative criterion to assess amino acid compositional extremes relative to a reference protein set is proposed and applied. Invariants of amino acid usage relate mainly to the central range of quantile distributions, whereas contrasts occur mainly in the tails of the distributions, especially contrasts between eukaryote and prokaryote species. Influences from genomic constraint are evident, for example, in the arginine:lysine ratios and the usage frequencies of residues encoded by G + C-rich versus A + T-rich codon types. The structurally similar amino acids, glutamate versus aspartate and phenylalanine versus tyrosine, show stochastic dominance relationships for most species protein sets favoring glutamate and phenylalanine respectively. The quantile distribution of hydrophobic amino acid usages in prokaryote data dominates the corresponding quantile distribution in human data. In contrast, glutamate, cysteine, proline and serine usages in human proteins dominate the corresponding quantile distributions in Escherichia coli. E. coli dominates human in the use of basic residues, but no dominance ordering applies to acidic residues. The discussion centers on commonalities and anomalies of the amino acid compositional spectrum in relation to species, function, cellular localization, biochemical and steric attributes, complexity of the amino acid biosynthetic pathway, amino acid relative abundances and founder effects.


Relationships between sequence and structure for the four-alpha-helix bundle tertiary motif in proteins. The sequences of four-alpha-helical bundle proteins are characterized by a pattern of hydrophilic and hydrophobic amino acids which is repeated every seven residues. At each position of the heptad repeat there are specific constraints on the amino acid properties which result from the topology of the tertiary motif. These constraints give rise to patterns of amino acid distribution which are distinct from those of other proteins. The distributions in each of the heptad positions have been determined by a statistical analysis of structural and sequence data derived from seven families of aligned protein sequences. The constitution of each position is dominated by a very small number of different amino acids, with the core positions consisting overwhelmingly of Leu and Ala. The positional preferences of the individual amino acids can be generally interpreted in terms of residue properties and topological constraints. The potential for four-alpha-helix bundle folding is reflected primarily in the pattern of residue occurrence in the heptad and not in the overall amino acid composition of the protein. Possible applications of this analysis in structure predictions, sequence alignments and in the rational design and engineering of four-alpha-helical bundle proteins are discussed.


Free energy perturbation study on a Trp-binding mutant (Ser88-->Cys) of the trp-repressor. The Ser88-->Cys mutant of the trp-repressor showed a lower affinity for the corepressor than the wild-type repressor [delta delta G = 1.7 +/- 0.3 kcal/mol, Chou and Matthews (1989) J. Biol. Chem., 264, 18314-18319]. A molecular dynamics/free energy cycle perturbation study was performed to understand the origin of the decreased affinity. A value (delta delta G = 1.58 +/- 0.28 kcal/mol) comparable with the experimental value was obtained by the simulation. Free energy component analysis revealed that destabilization of the van der Waals interaction between Ser88 and Trp109 (corepressor) mainly contributed to the decreased affinity of the mutant. The rotational transition of the hydroxyl (sulfhydryl) group of Ser88 (Cys88) during the simulations affected the contributions of Arg84 and water to the free energy change in the aporepressor and those of Arg84 and Trp109 to that in the holorepressor. However, the contributions from different residues compensated each other, and the total free energy changes were almost invariable in the various simulations.


Single amino acid substitutions can further increase the stability of a thermophilic L-lactate dehydrogenase. Lactate dehydrogenases are of considerable interest as stereospecific catalysts in the chemical preparation of enantiomerically pure alpha-hydroxyacid synthons. For such applications in synthetic organic chemistry it would be desirable to have enzymes which tolerate elevated temperatures for prolonged reaction times, to increase productivity and to extend their applicability to poor substrates. Here, two examples are reported of significant thermostabilizations, induced by site-directed mutagenesis, of an already thermostable protein, the L-lactate dehydrogenase (EC 1.1.1.27, 35 kDa per monomer subunit) from Bacillus stearothermophilus. Thermal inactivation of this enzyme is accompanied by irreversible unfolding of the native protein structure. The replacement of Arg171 by Tyr stabilizes the enzyme against thermal inactivation and unfolding. This stabilizing effect appears to be based on improved interactions between the subunits in the core of the active dimeric or tetrameric forms of the enzyme. The thermal stability of L-lactate dehydrogenase variants with an active site Arg residue, either in the 171 (wild-type) or in the 102 position, is further increased by sulfate ions. The two stabilizing effects are additive, as found for the Arg171Tyr/Gln102Arg double mutant, for which the stability of the protein in 100 mM sulfate solution reaches that of L-lactate dehydrogenases from extreme thermophiles. All mutant proteins retain significant catalytic activity, both in the presence and absence of stabilizing salts, and are viable catalysts in preparative scale reactions.


Analysis of several key active site residues of ricin A chain by mutagenesis and X-ray crystallography. Active site residues of ricin A chain were analyzed by site-directed mutagenesis and X-ray diffraction to help assess their roles in the mechanism of action of this toxic N-glycosidase enzyme. Arg180 is thought, from X-ray studies, to protonate the adenine substrate at N3; this facilitates bond cleavage and is crucial to the mechanisms of action. The residue was converted to Gln and initial rate data measured. Km for the mutant is not significantly affected, increasing only 2-fold. The kcat, however, is decreased approximately 1000-fold. This is consistent with a simple interpretation that Arg180 is involved more in transition state stabilization than in substrate binding. Tyrosines 80 and 123 are known from X-ray models to stack on either side of the substrate adenine ring. When they were each converted to serine overall activity was reduced 160- and 70-fold respectively against ribosomes from Artemia salina. These effects are each approximately 10 times greater than when the residues were previously converted to phenylalanines. Sufficient protein for the Tyr80 to Phe mutant was obtained to carry out an X-ray analysis. Together with mutagenesis data, the structure suggests that the invariance of the two active site Tyr residues is largely caused by structural stability.


Triple point mutation Asp10-->His, Asn101-->Asp, Arg148-->Ser in T4 phage lysozyme leads to the molten globule. The triple amino acid replacement (Asp10-->His, Asn101-->Asp, Arg148-->Ser) in T4 phage lysozyme was carried out by site-directed mutagenesis. At acid pH (2.7) the mutant is in a conformational state with the properties of the molten globule: (i) the mutant protein molecule is essentially compact; (ii) its CD spectrum in the near UV region is drastically reduced in intensity as compared with the wild type protein spectrum; (iii) the CD spectrum in the far UV region indicates the presence of pronounced secondary structure in the mutant; (iv) unlike the wild type protein the mutant protein can bind the hydrophobic fluorescent probe, ANS.


Probing the role of threonine and serine residues of E. coli asparaginase II by site-specific mutagenesis. Site-specific mutagenesis has been used to probe amino acid residues proposed to be critical in catalysis by Escherichia coli asparaginase II. Thr12 is conserved in all known asparaginases. The catalytic constant of a T12A mutant towards L-aspartic acid beta-hydroxamate was reduced to 0.04% of wild type activity, while its Km and stability against urea denaturation were unchanged. The mutant enzyme T12S exhibited almost normal activity but altered substrate specificity. Replacement of Thr119 with Ala led to a 90% decrease of activity without markedly affecting substrate binding. The mutant enzyme S122A showed normal catalytic function but impaired stability in urea solutions. These data indicate that the hydroxyl group of Thr12 is directly involved in catalysis, probably by favorably interacting with a transition state or intermediate. By contrast, Thr119 and Ser122, both putative target sites of the inactivator DONV, are functionally less important.


Construction and characterization of a single polypeptide chain containing two enzymatically active dihydrofolate reductase domains. A single polypeptide chain containing two dihydrofolate reductase (DHFR) sequences from Escherichia coli was constructed to determine if a repeat sequence fusion protein could be expressed in an active form. The possibility that intersequence interactions could play a significant role for this enzyme is suggested by the results of Hall and Frieden (1989, Proc. Natl Acad. Sci. USA, 86, 3060-3064) who observed a substantial decrease in the yield of active enzyme when folded in the presence of a large C-terminal fragment. The fusion protein [DHFR(Cys152Glu)--Ile--DHFR (Met1Gln)] was efficiently expressed in E. coli cells and has an activity which is twice that of the wild-type enzyme in the standard assay. The Michaelis constants of the fusion protein for the substrate, dihydrofolate and the cofactor, NADPH, are essentially unchanged from those of the wild-type protein. The urea-induced in vitro unfolding reaction of the fusion protein at low concentrations was found to be fully reversible and follow a three state model, suggesting that the two domains unfold independently. At higher protein concentrations the unfolding transition broadened and shifted to a higher urea concentration. Size-exclusion chromatography results are consistent with the formation of aggregates at the higher protein concentration, even in the absence of denaturant.


Development of an optimized refolding process for recombinant Ala-Glu-IGF-1. Denatured and reduced N-terminal extended insulin-like growth factor-1 (AE-IGF-1) was purified from Escherichia coli extracts and subjected to in vitro folding. The renaturation process was shown to be a function of the redox potential of the solution. Folding by different methods had no significant effect on the renaturation. A maximal yield of 60% (w/w) was obtained. The folded AE-IGF-1 was enzymatically converted to IGF-1. The major by-product (20% w/w) was identified as scrambled IGF-1. Enzymatic digestion at alkaline and acidic pH suggested two possible disulphide bond arrangements; (i) Cys6-Cys47, Cys18-Cys61, Cys48-Cys52; or (ii) Cys6-Cys52, Cys18-Cys61, Cys47 and Cys48 being in their reduced forms. Energy minimization and molecular modelling suggested that the scrambled IGF-1, having reduced cysteines at positions 47 and 48, was the energetically most stable conformation of the two.


Oxygen binding and other physical properties of human hemoglobin made in yeast. Wagenbach et al. (1991, BioTechnology, 9, 57-61) have recently developed a system for producing soluble recombinant tetrameric hemoglobin in yeast: hemoglobin begins to appear 4-5 h after induction with galactose, alpha- and beta-globin chains fold in vivo and endogeneously produced heme is incorporated into hemoglobin tetramers. We have further characterized the oxygen-binding properties, as well as the tetramer stability, of recombinant human Hb A made in yeast. After purification by ion-exchange chromatography, a single band at the same position as normal human Hb A was obtained using cellulose acetate electrophoresis. Although the oxy and deoxy forms of purified recombinant Hb A made in yeast were spectrophotometrically identical to native human Hb A, the oxygen-binding curve was shifted slightly left of that for native human Hb A. Further purification of recombinant hemoglobin by FPLC revealed two fractions: one (fraction B) with low cooperativity and high oxygen affinity, and the other (fraction A) with almost identical cooperativity and oxygen affinity compared with native human Hb A. The Bohr effect of fraction A was also identical to native human Hb A. Hemoglobin in fraction B with lowered cooperativity precipitated approximately 1.5 times faster than normal human Hb A during mechanical agitation, while hemoglobin in fraction A with normal cooperativity precipitated with kinetics identical to native human Hb A. These results suggest that some of the recombinant molecules made in yeast fold improperly, and that these molecules may exhibit decreased cooperativity for oxygen binding and decreased stability.(ABSTRACT TRUNCATED AT 250 WORDS)


Expression of the phosphorylase kinase gamma subunit catalytic domain in Escherichia coli. The catalytic subunit of phosphorylase b kinase (gamma) and an engineered truncated form (gamma-trc, residues 1-297) have been expressed in Escherichia coli. The truncated protein included the entire catalytic domain as defined by sequence alignment with other protein kinases but lacked the putative calmodulin binding domain. Full-length protein was produced in insoluble aggregates. Some activity was regenerated by solubilization in urea and dilution into renaturating buffer but the activity was found to be associated with a smaller molecular weight component. Full-length protein could not be refolded successfully. The truncated gamma subunit was produced in the soluble fraction of the cell as well as in inclusion bodies. The insoluble protein was refolded by dilution from urea and purified to homogeneity, in a one step separation on DEAE-Sepharose to give a protein mol. wt 32,000 +/- 2000 with a high sp. act. of 5.3 mumol 32P incorporated into phosphorylase b(PPB)/min/nmol. Kinetic parameters gave Km for ATP 46 +/- 3 microM and Km for PPb 27 +/- 1 microM. The sp. act. and the Km values are comparable to those observed for the activated holoenzyme and indicate that the gamma-trc retains the substrate recognition and catalytic properties. The ratio of activities at pH 6.8/8.2 was 0.84. gamma-trc was inhibited by ADP with a Ki of 52 microM and was sensitive to activation by Mg2+ and inhibition by Mn2+, properties that are characteristic of the holoenzyme and the isolated gamma subunit. Calmodulin which confers calcium sensitivity on the isolated gamma subunit had no effect on the enzymic properties of gamma-trc.(ABSTRACT TRUNCATED AT 250 WORDS)


Computer-aided gene design.

Computer-aided gene design. A computer program, which runs on MS-DOS personal computers, is described that assists in the design of synthetic genes coding for proteins. The goal of the program is the design of a gene which (i) contains as many unique restriction sites as possible and (ii) uses a specific codon usage. The gene designed according to the criteria above is (i) suitable for 'modular mutagenesis' experiments and (ii) optimized for expression. The program 'reverse-translates' protein sequences into degenerated DNA sequences, generates a map of potential restriction sites and locates sequence positions where unique restriction sites can be accommodated. The nucleic acid sequence is then 'refined' according to a specific codon usage to remove any degeneration. Unique restriction sites, if potentially present, can be 'forced' into the degenerated nucleic acid sequence by using 'priority codes' assigned to different restriction sequences.


Metabolic regulations and biological functions of phospholipids in Escherichia coli. Extensive genetic and biochemical studies in the last two decades have elucidated almost completely the framework of synthesis and turnover of quantitatively major phospholipids in E. coli. The knowledge thus accumulated has allowed to formulate a novel working model that assumes sophisticated regulatory mechanisms in E. coli to achieve the optimal phospholipid composition and content in the membranes. E. coli also appears to possess the ability to adapt phospholipid synthesis to various cellular conditions. Understanding of the functional aspects of E. coli phospholipids is now advancing significantly and it will soon be able to explain many of the hitherto unclear cell's activities on the molecular basis. Phosphatidylglycerol is believed to play the central role both in metabolism and functions of phospholipids in E. coli. The results obtained with E. coli should undoubtedly be helpful in the study of more complicated phospholipid metabolism and functions in higher organisms.


Cytotoxic and cytostatic effects of antitumor agents induced at the plasma membrane level. A variety of antitumor agents inhibit cell proliferation by interacting with the plasma membrane. They act as growth factor antagonists, growth factor receptor blockers, interfere with mitogenic signal transduction or exert direct cytotoxic effects. The P-glycoprotein encoded by the MDR1 gene represents a transmembrane protein which catalyzes the efflux of various antitumor agents. This membrane protein is the target of compounds acting as Multi-Drug Resistance (MDR)-modulators. Finally, several established antitumor agents which are considered to represent DNA-targeted drugs, including anthracyclines, platinum complexes and alkylating agents, cause a variety of membrane lesions. Their contribution to the antitumor activity of these drugs is discussed.


Natural products which interact with tubulin in the vinca domain: maytansine, rhizoxin, phomopsin A, dolastatins 10 and 15 and halichondrin B. This paper summarizes published data on the interactions of tubulin with antimitotic compounds that inhibit the binding of vinca alkaloids to the protein. These are all relatively complex natural products isolated from higher plants, fungi and marine invertebrate animals. These agents are maytansine, rhizoxin, phomopsin A, dolastatins 10 and 15 and halichondrin B and their congeners. Effects on tubulin polymerization, ligand binding interactions and structure-activity relationships are emphasized.


Dose-response relationships with antihypertensive drugs. A variety of antihypertensive drugs have been introduced into clinical practice at excessively high dose. Examples include most thiazide diuretics, propranolol, oxprenolol, atenolol, methyldopa, hydralazine and captopril. These very high doses have usually resulted from studies in which doses have been increased at regular intervals until the desired antihypertensive effect has been achieved or until unacceptable adverse effects have resulted. Frequently the starting doses were too high and the intervals between dose adjustment too short. In many cases these large doses resulted in unnecessary adverse effects--the adverse biochemical effects of thiazide diuretics, nephrotic syndrome, taste disturbances and neutropenia with captopril, the lupus syndrome with hydralazine and the central nervous system effects of methyldopa. Parallel group design with single doses and sufficient statistical power to distinguish between the upper and lower ends of the antihypertensive dose-response relationship should replace the dose-escalating design.


Reporting the size of effects in research studies to facilitate assessment of practical or clinical significance. "Statistically significant" results may lack practical or clinical significance, and the description of results in reports of research studies is frequently incomplete or misleading in presentation of data necessary to assess such significance (effect sizes). Various common presentations are discussed, and one method of presentation of results is proposed that not only encompasses all the others, but enhances the scope of useful information conveyed in a research report. The results of the Infant Health and Development Program (IHDP) are used to illustrate the method.


Steroid hormones and CNS sexual dimorphisms modulate symptom expression in Tourette's syndrome. We present our hypothesis that various steroid hormones play an important role in the symptom expression of Gilles de la Tourette's syndrome (TS) and that androgenic hormones, in particular, are likely to exacerbate symptoms of the disorder. We review the clinical evidence supporting our hypothesis. Sex steroids establish brain sexual dimorphisms early in CNS development, and we suggest mechanisms whereby androgenic and other hormonal changes later in human development might act at dimorphic brain regions to influence the natural history of TS. Finally, we discuss the various ways in which neuroendocrine studies might assist in genetic and neurobiologic research programs in TS.


A critical review of menstrual synchrony research. Two experiments and three studies reported a significant level of menstrual synchrony after subjects had been treated with applications of axillary extract from a donor subject or after subjects have spent time together. Four studies failed to replicate these results. A comparison of the studies shows the only consistent difference is that those studies not finding menstrual synchrony reported problems with subjects who had irregular cycle lengths, while those finding menstrual synchrony reported no such problems. All experiments and studies were based on the methods and research design introduced by McClintock (1971). Three errors are inherent in research based on her model: (1) an implicit assumption that differences between menses onsets of randomly paired subjects vary randomly over consecutive onsets, (2) an incorrect procedure for determining the initial onset absolute difference between subjects, and (3) exclusion of subjects or some onsets of subjects who do not have the number of onsets specified by the research design. All of these errors increase the probability of finding menstrual synchrony in a sample. One or more of these errors occurred in the experiments and studies reporting synchrony; no significant levels of menstrual synchrony occur when these errors are corrected. Menstrual synchrony is not demonstrated in any of the experiments or studies.


Clinical relevance of antibodies against serotonin and gangliosides in patients with primary fibromyalgia syndrome. The fibromyalgia syndrome (FMS) is a non-articular rheumatic disorder associated with disturbances in serotonin metabolism. In order to evaluate whether patients with FMS suffer from an autoimmune disorder, we tested sera from 50 clinically well-defined FMS patients for non-organ-specific and organ-specific antibodies by enzyme-linked immunosorbent assay and immunofluorescence test. Common antibodies against nuclei, mitochondria, and microsomes were not increased in these patients compared to healthy controls. However, 74% had antibodies against serotonin and gangliosides. The clinical and diagnostic relevance of these antibodies is supported by the absence of anti-serotonin antibodies in other rheumatic disorders such as rheumatoid arthritis, polymyalgia rheumatica, and collagen diseases. These antibodies may belong to the group of antireceptor antibodies, considering the fact that gangliosides are an important component of the serotonin receptor. It remains to be determined whether these antibodies are of pathogenetic relevance, interfering with serotonin binding and thereby inducing symptoms associated with FMS.


Pituitary-gonadal function during sleep in healthy aging men. There is limited information on the relation between age-related changes in pituitary-gonadal function and sleep physiology in older men. In this cross-sectional study of 67 healthy volunteers free from sleep complaints, aged 45-75 yr, we (1) assessed peak fluctuations and hourly variations in plasma testosterone, LH and prolactin sampled every 20 min during sleep, and (2) explored the relation between sleep parameters, respiratory and periodic leg movement disturbances, and circulating concentrations of the aforementioned hormones. We hypothesized that alterations in sleep architecture or presence of sleep disorders may contribute to hormonal variations in aging subjects. Bioavailable testosterone decreased and LH increased with age, but there were no differences in total testosterone and prolactin and no major changes in peak hormonal release. There were positive associations, independent from the age effect, between sleep efficiency, decreased latency to onset of REM activity, and number of REM episodes, and circulating testosterone. Sleep-disordered breathing significantly increased with age. The degree of respiratory disturbance was associated with decreased overnight plasma bioavailable testosterone, but this relationship lost its significance after age-adjustment. The findings demonstrate a decrease in gonadal function during sleep in healthy aging men and suggest that changes in sleep efficiency and architecture are associated with alterations in gonadal activity in these older individuals.


Apomorphine stimulation of vasopressin- and oxytocin-neurophysins. Evidence for increased oxytocinergic and decreased vasopressinergic function in schizophrenics. Apomorphine challenge tests (0.5 mg SC) were performed in 14 normal male volunteers and in 9 male schizophrenic inpatients, drug-free for at least 2 wk. In the normal volunteers, apomorphine induced an increase of serum growth hormone (GH) (maximum at 40 min), of vasopressin-neurophysin (hNpI) (maximum at 20 min), and oxytocin-neurophysin (hNpII) (maximum at 20 min). The release of neurophysins was independent of digestive side effects. In the schizophrenics, the GH level and release pattern were similar to those in the controls. The basal level of hNpI was reduced (t0: 0.42 +/- 0.1 ng/ml in the schizophrenics and 0.66 +/- 0.05 ng/ml in the controls, p < 0.02). In contrast, the basal level of hNpII was increased (3.34 +/- 0.04 ng/ml in the schizophrenics to 0.92 +/- 0.21 ng/ml in the controls, p = 0.001). The response to apomorphine was blunted, with no significant release of hNpI or of hNpII. Although the hNpII data are consistent with an increased dopaminergic tone, the psychopathological meaning of the increased basal oxytocinergic and decreased vasopressinergic functions remains to be defined.


The effects of menstrual phase and nicotine abstinence on nicotine intake and on biochemical and subjective measures in women smokers: a preliminary report. Nicotine intake, menstrual and smoking withdrawal symptomatology, and baseline cortisol and MHPG were assessed in nine women smokers under conditions of ad lib smoking and overnight abstinence in three menstrual phases (early follicular, mid-to-late follicular, and late luteal). A trend towards higher nicotine intake (p < 0.10) was observed in the mid-to-late follicular phase. Although menstrual symptomatology was not significantly elevated during the smoking abstinence condition overall, abstinence appeared to prevent the normal reduction in symptomatology during the mid-to-late follicular phase that occurred under conditions of ad lib smoking. Menstrual and withdrawal symptoms were highly correlated, and both were most pronounced during the late luteal/abstinence condition. The smoking-specific item "craving" reflected this pattern, though in attenuated form, suggesting that the observed exacerbation of withdrawal symptomatology was not simply due to generalized dysphoria, as queried in both instruments. MHPG was significantly elevated in the late luteal phase, whereas cortisol was significantly higher during ad lib smoking than during abstinence and tended to be highest in the mid-to-late follicular phase. Further investigation will be needed to determine the functional significance of these findings for understanding and treating smoking in women.


Testosterone and erectile function, nocturnal penile tumescence and rigidity, and erectile response to visual erotic stimuli in hypogonadal and eugonadal men. Further evidence that nocturnal erections are androgen-dependent and erectile responses to visual erotic stimuli are androgen-independent is presented from six men with secondary hypogonadism and six eugonadal controls. Erections during sleep were substantially less in the hypogonadal men, in terms of both tumescence and rigidity. In response to visual erotic stimuli, the percentage increase in circumference over baseline and the increase in rigidity were similar for the two groups.


Coping and the ineffectiveness of coping influence the outcome of in vitro fertilization through stress responses. The effect of a coping-ineffectiveness of coping construct and of psychoendocrine stress responses upon the outcome of in vitro fertilization treatment was investigated in 40 women. Women with a high Zung depression score, high active coping, high avoidance, and a high expression of emotion have lower pregnancy rates. The mechanisms for this personality effect are not clear, although the desensitization-stimulation process (FSH, E2 concentrations) seems to be involved. The psychoendocrinological responses to the stress of oocyte retrieval and embryo transfer are important: Women with high anticipatory state anxiety levels and high anticipatory cortisol concentrations have lower pregnancy rates. The influence of prolactin stress concentrations is unclear: Women with high prolactin concentrations seem to have more oocytes but lower fertilization rates.


Psychosocial aspects of hyperprolactinemia. Fourteen mildly hyperprolactinemic women and 14 matched controls were compared with respect to biographical data, self-reported emotional and somatic well-being, and cortisol production. The patients had significantly more often experienced a separation from their parents in childhood. No differences were found for cortisol levels and emotional and somatic well-being. Future studies also should focus on personality, coping, and defense mechanisms in order to explain these contrasting findings.


Changes in burying behavior during the estrous cycle: effect of estrogen and progesterone. This study demonstrates changes in cumulative burying behavior during various phases of the rat estrous cycle. Low levels of burying behavior were observed during late proestrus. Similar burying behavior levels among females tested in early proestrus, metestrus or diestrus and ovariectomized females were found. In ovariectomized females, treatment with estrogen (E) produced a slight, non-significant reduction in burying behavior. In contrast, progesterone (P) treatment resulted in a dose-dependent, statistically significant decrease in time spent burying. The combined treatment of E and P produced no effect. These data are discussed from the standpoint of the putative anxiolytic effect of P.


Effects of chronic corticosterone treatment on electrophysiological and behavioral measures in the rat. The electrophysiological and behavioral effects of daily oral exposure to a corticosterone or vehicle solution was evaluated in 20 male Wistar rats over a 10-wk period. Evaluation of the rats' behavior in an open field apparatus, as well as in automated locomotor cages, revealed no significant differences between steroid-treated and control animals following 5-6 wk of exposure. No differences in mean EEG power, as estimated by spectral analysis of cortical and dorsal hippocampal recordings, were observed between the two groups following 8 wk of exposure. However, some increases in EEG "stability" were noted in the corticosterone-treated rats. At 9 wk, responses to auditory stimuli, as assessed by evoked responses, in cortex and dorsal hippocampus were also found to be unaltered by corticosterone exposure. These studies suggest that exposure to daily oral corticosterone, in the doses used, over a period of 2-3 mo is not associated with gross electrophysiological or spontaneous behavioral effects in the brain areas assessed.


Cortisol concentrations and the social significance of rank instability among wild baboons. Previous work has shown that dominant primates in stable social hierarchies in a number of species often have low basal cortisol concentrations, relative to subordinate individuals. In contrast, this trait appears to be lost during periods of social instability, probably reflecting the psychological stressfulness of the instability. The present study examined whether basal cortisol concentrations were elevated not only when the overall hierarchy was unstable, but also were elevated in individuals which, within a stable hierarchy, were nevertheless in the process of their own rank shifting. Study subjects were a population of male olive baboons living freely in a national reserve in East Africa, which could be anesthetized under conditions allowing for determination of basal cortisol concentrations. The instability of a particular rank was quantified by determining the percentage of dominance interactions that represented a reversal of the already established direction of dominance. Highly unstable relationships with the rest of the males in the hierarchy did not predict elevated basal cortisol concentrations in an individual. Instead, it was the stability of interactions with males close in rank (within three steps in the hierarchy of the individual) which predicted cortisol concentrations: the greater the percentage of interactions that were reversals with the three nearest lower-ranking males, the higher the basal cortisol concentrations in an individual. In general, high rates of such reversal interactions indicated that the male was being challenged for his more dominant position.(ABSTRACT TRUNCATED AT 250 WORDS)


Intracerebroventricular LHRH may serve as a discriminative stimulus in male rats. Male Wistar rats (N = 16) were trained to discriminate 5 micrograms/kg LHRH, injected intraperitoneally, from saline in a two-lever, food-reinforced drug discrimination procedure, with an injection-session interval of 45 min. Reliable discrimination of LHRH was acquired within 60 training sessions. Subsequent generalization tests in brain-cannulated animals showed dose-dependent and time-related partial substitution of intracerebroventricular LHRH for intraperitoneal LHRH (ventricle doses ranged from 25-400 ng, and the injection-session intervals ranged from 10-40 min). These results indicate that centrally administered LHRH may serve as a dose- and time-dependent discriminative stimulus in male rats.


[Psychology of male and female desire for children. Developmental conditions of narcissistic, depressive and creative aspects]. Conscious and unconscious determinants of the wish for a child deriving from early childhood are demonstrated. In this context the elaboration of phase-specific narcissistic mortifications in connection with the recognition or repression of ambivalence is given prime importance. The acceptance of the ambivalence and triangulation have the effect that the creative aspects in the later wish for a child are more powerful than the narcissistic or depressive parts.


[Pregnancy, labor and partnership relations in a family with a "retort baby". Follow-up of "IVF couples" and their children]. Nowadays, in vitro fertilisation can be judged as a relatively successful treatment in special cases of sterility. Success cannot be defined only by induction of pregnancy, but must also be taken into consideration the couple's and the "IVF-children's" personal situation. The main problem of IVF is the high multiple rate of nearly 20%, resulting in a higher frequency of preterm deliveries. This leads to higher perinatal mortality and more longterm deficiencies in these children. The women's attitude during pregnancy can be considered to be responsible. From a psychosomatic point of view (the husband's presence during delivery, breast feeding etc.) there are favourable preconditions for the "birth of the family." In most cases, the couples give a contented or good view of their partnership (self-assessment). Nearly 5% of them seem to be "disappointed" after the birth of the baby. The method of IVF is positively assessed from an overall point of view. But only half of the women do not keep this special method of procreation secret.


[Sterility--a woman's concern? Coping behavior and partnership structure of sterile couples of various diagnostic groups]. Three groups of sterile couples with functional, tubal and andrologically caused sterility were compared for the evaluation of sex- and diagnosis-dependent kinds of overcoming of their disease. Anamnestic data, anxiety, the coping strategy of sterility and as well the couple and personality structure are analysed. Independent of the organic cause of sterility the women showed a higher emotional reaction level (anxiety, coping stress) than their husbands. In all groups the "healthy" partners dominate. The subfertile men seem to be more subordinate, less engaged and interested and not so anxious as their wives and as the husbands of tubal sterile women. The healthy women with andrologically caused sterility present a highly emotional engagement in the overcoming and treatment of their disease. Possible emotional mechanisms and social stereotypes of self-presentation are discussed, which may cause the intense engagement of the women independent of the organic cause of sterility.


[A study of the psychosomatic aspects of endometriosis]. Based upon existing psychological studies of endometriosis, the hypothesis was tested if patients suffering from this disorder differ from other infertile females with respect to psychological characteristics. Using questionnaires as well as a semi-structured psychotherapeutic interview 38 patients with endometriosis and 18 females with tubal sterility were investigated. A comparison of both groups indicated a higher level of anxiety and some evidence for a somatic preoccupation in the endometriotic patients. The analysis of the interviews (which were judged by several independent raters) confirmed the hypothesis of gender role conflicts in combination with endometriosis. This conflict seemed to be characterized by a negative experience of menarche and puberty, early gynecological problems and negative sexual experiences. This constellation is illustrated using a typical case. Based upon these results, further studies of endometriosis using a psychosomatic perspective seem to be promising.


[Self concept and body image in involuntary sterility]. From theoretical reasons and clinical experience with infertile women, an impairment of the self-image and the body-image was to be expected with involuntarily childless people. Our hypothesis was tested in a sample of 107 subjects. 59 of them (f = 30, m = 29) were patients undergoing treatment for infertility. The two control groups consisted of 24 parents and 24 (voluntary) nonparents. Four instruments were used: 1. a modified version of the Role Construct Repertory Test according to Kelly (1955); 2. rating scales concerning different parental and non-parental roles; 3. the Questionnaire About One's Own Body by Strauss and Appelt (1983); 4. our Questionnaire About Problems Caused by Involuntary Childlessness. Contrary to what we expected, we neither found greater distances between self and ideal self nor an unfavourable body-image in involuntarily childless subjects. The male patients presented themselves even more self-confident and more attractive than the men of the control groups.


[Characteristics and problems of Balint groups with medical students]. For a period of seven years medical students have had the opportunity to attend Balint-seminars in an intensive training course in the field of "Medical Psychology and Psychotherapy" during their clinical education. In groups of 10-15 students the participants study conscious and subconscious aspects in the relationship between students and patients in the setting of their practical work in hospital. Some of these students additionally hold supporting conversations with mentally and psychosomatically ill patients. This takes place at the Psychotherapeutic Department and at the Department of Psychiatry, both at Innsbruck University, and is supervised in the Balint-seminars. In addition to this psychoanalytically oriented supervision theoretic knowledge (socio-psycho-somatic aspects of illnesses, subconscious aspects in the doctor-patient-relationship, phenomena of transference and counter-transference) is being brought across. In the students' Balint-seminars both patient-related self-experience and the reflection upon the students' social role in hospital acquire special importance. The development of this model of teaching and learning and the experiences which have been achieved over the last seven years are described in this article concerning the practicability for a patient centered model in the education of medical students.


[Does the endless increase in knowledge finally lead to a change in attitude? On the distinction between instruction and education in medicine]. In view of the overwhelming increase in our knowledge of the sciences, a call for desirable integration is being made from the practical standpoint. A change of attitude is being recommended to help the practitioner let his daily dealing with any one patient be less determined by general obligations and more by concrete necessities, thereby creating a balance with a firm hold on reality. An appropriate education should not be understood as bare instruction in established knowledge and abilities but requires above all real, practical training which also considers how we might deal thoughtfully with the fruits of our knowledge. This way of thinking cannot itself be taught as a subject of knowledge. A differentiation between education and instruction is suggested, questioning the tendency often uncritically to "force into line", thus allowing a value-determining new orientation. Psychotherapy--especially with the practical experience of relationships on which it is based--has to be aware of its specific function within the entire scope of human medicine and the importance of and dangers to this function are discussed.


[Psychological factors of non-ulcer dyspepsia]. Given the absence of any demonstrable organic reason for non-ulcer dyspepsia, and the well known fact, that the psyche influences stomach function, it is widely held, that psychological factors cause NUD. To now, studies are concerned with the psychopathology and personality of NUD-patients, their illness behaviour, and with the relation between stress and abdominal pain. A critical review of these studies revealed, that among the psychological variables mainly anxiety and illness behaviour seems to play a central role in NUD. However, future studies should focus more on the distinction towards other functional disorders and on the differentiation within the heterogeneous group of NUD-patients (especially with regard to physiological variables). Besides this, it seems rewarding to examine the so far scientifically neglected group of subjects with abdominal pain, who do not contact a physician.


[Coping with illness by chronically ill adolescents and young adults--an empirical study]. From June 1990 to January 1991 86 chronically ill adolescents and young adults who had come to the vocational assessment unit of the rehabilitation center or for vocational guidance to the rehabilitation hospital, both in Neckargemünd/Germany, were examined with regard to their coping with their illnesses. The Freiburg questionnaire for coping with illness was applied, and the Trait-instruction was given because persons with inborn disabilities were part of the sample. Also, the type of illness or disability and motorial handicap as well as the non-verbal intelligence were included. The results of three different medical diagnosis groups don't show any differences in the coping with illness. Persons with motorial handicaps are able to cope with their disabilities as well as persons without motorial handicaps. Adolescents and young adults with inborn or early acquired illness/handicap show a greater loss of confidence in the medical doctors than persons who were taken ill at the age of 6 or later.


["... and found no shade". Coping processes of patients with erythropoietic protoporphyria]. Coping with disease was studied in a group of ten persons suffering from erythropoietic protoporphyria (EPP), a chronic congenital metabolic disorder that manifests itself in extreme sensitivity to ultraviolet light. Sufferers experienced medical prophylaxis as ineffective or counterproductive. The BEFO technique (Berner Bewältigungsformen BEFO, 3 dimensions, 27 categories) was used in assessing the coping strategies. The sufferers' interviews were evaluated on the basis of transcripts. Stressors and respective coping strategies were defined and analysed for each person individually. Sufferers are confronted with their disease virtually every day. For each stressor the set of strategies tends to be specific either to the disease, the environment or it may reflect personality traits. Most of the sufferers did not develop an effective mode of adaptive behavior, i.e. coping with the pain/stigma dilemma, until they passed their third decade. While it undeniably presents an intense personal challenge, coping with disease must be seen to include major societal aspects as well.


[Attitude to death and control behavior of medical students--a cross sectional study]. Within the scope of a cross-section study the Fear of Death Questionnaire (Hensle 1977), the Semantic Differential of the term Death (Potthoff 1980) and the IPC questionnaire (Krampen 1981) were submitted to n = 186 first- and second-year medical students and to n = 151 third- and fourth-year medical students. This was to trace the question how far the attitude toward death and the locus of control of medical students vary in the course of their education. In comparison with most of other respective publications our paper did not show any significant changes of their attitude toward death and their locuis of control neither. After more detailed analysis of the data discerning consideration of the fear of death questionnaire mentioned above is to be demanded prior to further use in medical fields. At least in view of medical students it's value regarding the construct validity is to be questioned. Concerning the Semantic Differential at least one adjective pair should be eliminated in future.


Tuberculosis in patients infected with human immunodeficiency virus 1. A retrospective multicentre study of 123 cases in France. The Groupe des Infectiologues du Sud de la France. In order to study the epidemiological, clinical, and progressive characteristics of TB in HIV-infected individuals, a retrospective study was conducted in nine infectious disease centres of university hospitals located in the southern half of France. Among the 5730 HIV-seropositive in- and out-patients, 123 (2.1 per cent) had TB (121 infections caused by M. tuberculosis, 2 by M. bovis). Tuberculosis was pulmonary in 53 patients (43.1 per cent), extrapulmonary in 36 patients (29.3 per cent), and combined in 34 patients (27.6 per cent). There was no statistically significant difference among these three locations as to the mean CD4 count/mm3 (160 +/- 17), the type of antituberculosis therapy, the length of treatment (10.8 +/- 0.6 months) and the outcome. Fifty-two (45.2 per cent) patients received an initial antituberculosis therapeutic regimen of four drugs: isoniazid, rifampicin, ethambutol, pyrazinamide; 54 (46.9 per cent) were started on three drugs: isoniazid, rifampicin, ethambutol; and nine (7.8 per cent) received a two-drug combination: isoniazid, rifampicin. Fourteen of 75 patients subsequently received secondary preventive therapy. The mean follow-up time was 252 +/- 290 days. Clinical healing was obtained in 57.7 per cent of patients. Forty-six patients died, 33 during treatment: 23 from AIDS and eight from TB (in the first 3 weeks of treatment). Five patients suffered from relapses due to poor treatment compliance. Patients had a good prognosis if tuberculosis was diagnosed early.


[Reminiscence therapy with the elderly]. Extending the possibilities of psychotherapeutic treatment, reminiscence therapy and life review seem to be especially suited to help elderly patients cope with crisis or depression. However, there are still many differences in methods and techniques applied. In this article, the role of the past in depression, previous research on reminiscence therapy as well as its possible goals and methods are considered. An example of reminiscence group therapy in a psychogeriatric day hospital is presented.


[The complexity problem and reductionist solutions--critical comments from the psychoanalytic viewpoint]. We refer to the essentials of the complexity of psychosomatic and psychoneurotic phenomena and how to comprehend this complexity. Measurement is called in question as a possibility to describe psychic phenomena. We make a suggestion to preserve the advantages and to overcome the disadvantages (selective awareness, no generalization, no intersubjective validitation) of clinical psychoanalytic research work.


Renal disease associated with circulating antineutrophil cytoplasm activity. We report our detailed observations on a group of 30 consecutive patients with renal disease, histologically demonstrated glomerulitis or necrotizing vasculitis, and circulating antineutrophil cytoplasm activity (ANCA). The annual incidence of ANCA-related renal disease was seven cases per million population. The sensitivity of serum ANCA for histologically proved glomerular vasculitis was 79 per cent, with a specificity of 87 per cent. Most patients responded to treatment with cyclophosphamide and steroids but complications of therapy occurred in just over half the patients and were serious in 20 per cent. Actuarial survival at 1 year was 60 per cent. Age and dialysis requirement did not influence outcome and the only identified adverse prognostic factor was hypoxic lung disease. We conclude that the association of ANCA with renal disease is not rare and that positive serology accurately identifies a homogeneous group of patients with similar clinical, histological, and prognostic features. Separation of these patients into those with the disease entities of Wegener's granulomatosis and microscopic polyarteritis is not straightforward on clinical and histological criteria, and such a distinction does not yield useful therapeutic or prognostic information. Simple urinalysis should always be carried out in patients with undiagnosed systemic illness in order to identify renal disease. ANCA-related renal disease can be treated successfully with cyclophosphamide and steroids and elderly patients should not be excluded from treatment, including dialysis if necessary. The ANCA test is simple and quick to perform and, in the appropriate clinical setting, accurately identifies patients who may benefit from immunosuppressive treatment before a histological diagnosis can be established.


[Concepts of anthroposophic psychiatry and their contribution to understanding schizophrenia]. A concept of central importance in alternative forms of psychiatry, namely the concept of the etheric body, is elaborated in reference to disturbed body sensations of schizophrenic patients. In the non-orthodox approach the etheric body, i.e. a spatial organisation of forces active in the organism that is perceived only under specific circumstances, is a mediating medium between body and soul. The concept of the etheric body proves to be associated with both, the still unsolved body-mind-problem and the problem of conceptualising psychic energy. Schizophrenia is interpreted as a disorder in which the connections between body, etheric body and mind have come loose.


Plasma exchange treatment and prognosis of Guillain-Barré syndrome. A retrospective analysis of case notes was undertaken for 52 patients presenting to Guy's Hospital with Guillain-Barré syndrome between August 1987 and September 1990. Twelve months after onset 61 per cent of patients had recovered completely, 35 per cent were still significantly disabled and two patients (4 per cent) had died. Forty-eight of the patients (92 per cent) were treated with plasma exchange. The frequency of morbidity related to this treatment was low, and plasma exchange was not responsible for either of the deaths. Outcome for all patients treated with plasma exchange between January 1985 and September 1990 was compared with that of 64 patients with Guillain-Barré syndrome seen in 1983 and 1984 who were not treated in this way. Time to walking unaided was significantly better (median 58 days compared with 86 days, p = 0.031), as was the median duration of ventilation (16.5 compared with 36 days, p = 0.004). Factors which had been found to predict an adverse outcome in previous studies (requirement for ventilation, age over 40 years, time to becoming bedbound less than 4 days, and small distally evoked abductor pollicis brevis muscle action potential) were not significantly associated with a poor prognosis in this study. The features associated with persisting disability were time to improvement more than 21 days, preceding diarrhoea and older age.


Frequency analysis of ventricular fibrillation and resuscitation success. In 56 patients, frequency analysis of the electrocardiogram of ventricular fibrillation exhibited power spectra with a distinct dominant frequency. The greatest success for resuscitation from ventricular fibrillation is recorded when ventricular fibrillation develops after the patient comes under coronary care. Of the 41 patients in whom the onset and first 8 s of ventricular fibrillation were artefact-free the mean dominant frequency of primary ventricular fibrillation (no cardiogenic shock or cardiac failure) in 21 patients was 6.2 +/- 0.2 Hz, significantly higher than the mean dominant frequency of the first 8 s of secondary ventricular fibrillation (cardiogenic shock or heart failure) (4.0 +/- 0.2 Hz, 20 patients, p = 0.0001). In these patients the peak-to-trough amplitude (ECG) of the first 8 s of ventricular fibrillation was similar in both primary and secondary ventricular fibrillation as was the mean duration of ventricular fibrillation prior to the first DC shock. There was a significantly lower success rate for resuscitation from secondary ventricular fibrillation (6 of 20 patients) compared with resuscitation from primary ventricular fibrillation (18 of 21 patients, chi 2 17.8, p = 0.001). Of the remaining 15 patients who were collapsed between 3 and 20 min before the arrival of the mobile coronary care unit, the dominant frequency of the first 8 s of ventricular fibrillation fell with increased duration of collapse (from 5.5 Hz at 3 min to a mean of 2.1 Hz at 20 min).(ABSTRACT TRUNCATED AT 250 WORDS)


Single-tooth home bleaching.

Single-tooth home bleaching. This article describes a simple but effective method of bleaching single vital discolored teeth. The patient applies a viscous 10% carbamide peroxide gel in a plastic mouth-guard designed to confine the gel only to the discolored tooth. This method has been effective for lightening vital teeth with calcified pulpal spaces.


Clinical significance of holes in gloves for dental use: a spectrophotometric analysis. The aim of this study on latex dental gloves was to establish whether there is any relationship between faults that are detected by filling with water and the entry of liquid into the gloves during use. Twenty-four gloves of different sizes were examined. Large and small holes randomly distributed on the index, middle, and ring fingers, were made in the gloves. The gloves were filled with water and squeezed to detect the amount of water escaping. A mass spectrophotometer was used with the same gloves to quantify the entry of an aqueous solution of potassium bichromate during work. The filling method was effective for revealing all faults in gloves, but it was not able to determine whether there would be fluid entry through the holes during work. While the size of the holes was not predictive for the amount of liquid entering the glove, adherence of the glove to the hand was. Holes of the same size allowed a greater entry of contaminated liquid in adherent gloves than in looser ones.


The importance of proximal curing in posterior composite resin restorations. This in vitro study compared the marginal adaptation of enamel-bonded mesio-occlusodistal composite resin restorations placed using two different insertion techniques (one-step and two-step) and three different curing techniques (occlusal using opaque matrix and wedge systems and interproximal using transparent matrix systems and either transparent, non reflecting, or transparent, laterally reflecting wedges). The micromorphology of the enamel-restoration interface and the marginal seal were evaluated after the restorations were exposed to mechanical and thermal stresses. Although the difference was not statistically significant, the marginal quality of the restorations placed with the two-step technique was better than that of the restorations placed with the one-step technique. The restorations cured from the interproximal direction had significantly better marginal adaptation than did restorations cured only from the occlusal direction. The quality among the groups of interproximally cured restorations was not significantly different, because all the restorative techniques that were evaluated resulted in generally poor marginal quality.


Identification of dental implants on radiographs. In the future, dentists will more frequently encounter patients who have dental implants. To use radiographs to identify implants that were previously inserted by other dentists, dentists have to be familiar with the detailed morphology of different products and types of fixtures as well as with the principles for formation of their radiographic images. In the present study, radiographic images of ten common dental implants were analyzed. Images varied with viewing angles. The influences of surface structures, such as threads, cuts, holes, perforations, and flutes, are demonstrated.


The effect of zinc chloride dentifrices on plaque growth and oral zinc levels. The antiplaque potential of zinc salts has been previously demonstrated. The purpose of the present investigation was to establish the effect of zinc chloride dentifrices on plaque growth and on the concentration of zinc in saliva and plaque. Zinc levels in saliva and plaque were measured by atomic absorption spectrophotometry. Elevated zinc levels were observed in saliva and in plaque for 1 hour after contact with a zinc chloride dentifrice. Increased concentrations of zinc were also observed in plaque residue. Further analysis of data showed that subjects with high rates of plaque growth benefited more from the zinc dentifrices than did those with low rates of plaque growth.


Resin bonding to wet substrate. II. Bonding to enamel. In part I of this study, it was reported that high shear bond strengths to dentin were obtained by using a particular dentin-enamel bonding system on wet dentin. Because it would be difficult to dry the enamel without drying the dentin, an investigation was undertaken to determine if the treatment of enamel surfaces with various phosphoric acid concentrations would be successful on wet enamel using the same bonding system. It was discovered that the bond strengths to etched and wet enamel using a particular dentin-enamel bonding system were equal to or higher than bond strengths to etched and dry enamel.


The effect of polymerization shrinkage during veneer placement. This study evaluated the relationship of polymerization shrinkage during composite resin veneer placement to direction of the polymerization light source. Fifty maxillary permanent incisors were obtained and divided into five groups of ten. Groups I and II had preparations placed in enamel. Groups III, IV, and V had preparations placed in dentin. In groups I and III, an unfilled bonding resin was placed and polymerized from the facial aspect, followed by placement and polymerization of a hybrid composite resin. Groups II and IV were initially polymerized from the lingual direction. In group V, the unfilled resin and hybrid composite resin were polymerized simultaneously from the facial aspect. Statistical analysis indicated that there was significantly less axial microgap formation during lingual polymerization when the preparation remained in dentin, but demonstrated that there was no statistically significant difference when the preparation remained in enamel.


Bond strength of glass-ionomer cement and composite resin combinations. The tensile bond strength to dentin was measured for three glass-ionomer cement and composite resin combinations: two light-curing glass-ionomer cements (Vitrebond and XR-Ionomer) and one traditional glass-ionomer cement (Ketac-Bond), two adhesive systems (Scotchbond, and XR-Bonding System), and a corresponding composite resin. The bond strength of this "sandwich" was also compared with that of the same cements used in bulk. Vitrebond showed a significantly higher bond strength in bulk than did the other two cements. Of the sandwiches, the XR-Ionomer and XR-Bond combination showed a bond strength significantly higher than that of the Vitrebond and Scotchbond or Ketac-Bond and Scotchbond combination. The fracture of the bond was mainly adhesive for Vitrebond, cohesive for XR-Ionomer when used in bulk and adhesive-cohesive when used in a sandwich, and cohesive for Ketac-Bond.


The relative shear bond strength of visible light-curing and chemically curing glass-ionomer cement to composite resin. The purpose of this study was to compare the shear bond strength to composite resin of a light-curing glass-ionomer cement with that of various chemically curing glass-ionomer cements. Light-cured composite resin cylinders were bonded to cylindrical glass-ionomer substrates after etching for 30 seconds with 37% phosphoric acid. Specimens were maintained in distilled water for 7 days and then thermocycled in water baths. One group of light-cured glass-ionomer cement substrates was not etched. The interfacial bond strength of these specimens was measured in shear. Cement shear strength was also evaluated. Statistical analysis showed the light-curing cement to have a significantly higher bond strength to composite resin than any of the chemically curing cements tested.


Three-dimensional MR vascular imaging of the spine using gadolinium-DTPA. To investigate the fine vascular structures in the spinal and paraspinal region, the authors performed three-dimensional GRASS scanning after the administration of contrast material. The scan sequence was sagittal volume scan, TR/TE 100/16, with a flip angle of 45 degrees. First-order gradient moment nulling was employed. Four normal volunteers and 31 patients were studied. Using this technique, longitudinal anterior epidural veins and vertebral arteries were clearly identified. Paraspinal fine vessels of slow to moderate flow, including dilated anterior spinal artery, radiculo-medullary vein, and perimedullary coronal venous plexus, were demonstrated in pathological cases. In addition, with processing of the volume data set, phlebographic projection images of the ladder-shaped anterior epidural venous system could be generated. This method provided more detailed information on epidural and intradural vessels than conventional MR imaging.


Correlation of CT patterns with histologic findings in parauterine masses. CT findings were correlated with histologic and surgical findings in 162 parauterine masses. CT findings were classified into four types and 14 patterns. These classifications were useful in the diagnosis and differential diagnosis of parauterine masses. Malignant ovarian tumors, uterine myogenic tumors, metastatic tumors, endometrial cysts, and benign cystadenoma revealed characteristic CT findings, making differential diagnosis possible on CT. Contrast enhancement of the solid part, bilaterality, and the presence of ascites were useful for differential diagnosis. Although CT is one of the major modalities for the diagnosis of intrapelvic mass lesions, MR imaging will be another important method for the delineation and characterization of these lesions in the future.


Uterine leiomyoma: correlation between signal intensity on magnetic resonance imaging and pathologic characteristics. To correlate the signal intensity of uterine leiomyoma with its pathologic characteristics, with particular emphasis on the fibrous component, 33 magnetic resonance (MR) examinations that revealed 93 leiomyomas were prospectively studied. All patients were imaged in axial and sagittal planes with different spin-echo pulse sequences to obtain T1-, T2-weighted, and proton density images. Nondegenerative leiomyomas (n = 62) showing a homogeneous signal of low intensity, and degenerative leiomyomas (n = 31) with a heterogeneous signal of variable intensity on T2-weighted images could be correlated. Histopathological assessment of fiber constitution and degeneration, and MR intensity were interpreted by independent observers. There was excellent accord between the averages for MR intensity, T2 relaxation time and fiber content, although the intensity values in each fiber grade showed a wide range. The greater the fiber content the lower the MR intensity on T2-weighted images, and the shorter the T2 relaxation time (p < 0.0001). In addition, the manner in which fiber distribution affected MR appearance was also elucidated. These data contribute guidelines for precise tissue differentiation of myogenic tumors on MR images, and for MR imaging tissue diagnosis of any lesion with a considerable fibrous element.


[The epidemiologist facing assessment of low risk]. Epidemiological studies on low risks involve a number of major methodological difficulties. This review defines the concept of low risk and emphasises the need to control all large, possibly disease-related risk factors, before low risk factors can be evaluated. This procedure is also essential in identifying confounding factors. There is a special need to evaluate statistical power in studies on low risk factors, and the representativeness of both cases and controls should be carefully verified, particularly in case-control studies. The need to control the researcher's wish bias and the main requirements for meta-analysis are also presented.


Thyroid carcinoma associated with hot nodule diagnosed by ultrasonography. A patient with thyroid carcinoma showing a hot nodule on radioiodine scintigraphy was examined by ultrasonography and was revealed to have occult carcinoma co-existing with adenomatous goiter. Ultrasonography should be performed to establish the diagnosis even if radioiodine scintigraphy reveals a hot nodule, as should fine-needle aspiration biopsy.


[Are accidents accidental? Prevention of injuries in children and adolescents]. This paper reviews the preventive strategies that have been used in different regions and countries to reduce the morbidity and mortality linked with injuries in children and adolescents. It is confined to programmes and initiatives of different kinds that have been evaluated. Strategies can concentrate on the circumstances leading to an accident, or on reducing the consequences of injury. They can be passive (window gates, speed limits, drug packaging) or active (use of helmets, training of young drivers). They can be specific (focusing on falls or burns) or non-specific (promoting low-risk behaviour in young people). In each case prevention must allow for the developmental stage of the target population, and be conceived and implemented through multidisciplinary approaches. It should be developed at national as well as regional and local levels. Finally, improvements must be made to the means of evaluating prevention strategies.


Confirmation of dialysate leakage by intraperitoneal administration of radioactive colloid. A 29-year-old man who had been on continuous ambulatory peritoneal dialysis (CAPD) was admitted to our hospital because of pleural effusion. Radioactive colloid studies with intraperitoneal administration revealed a pleuroperitoneal communication. After pleurodesis by the administration of fibrin glue and antiplasmin into the thoracic cavity, the pleural effusion did not reaccumulate and there was no evidence of pleuroperitoneal communication by radioactive colloid study.


Studies of cancer in migrant populations: methods and interpretation. The use of descriptive epidemiological data (collected without a view to investigating any specific hypothesis) to study the risk of cancer in populations which have migrated from one country to another is reviewed. Place of birth is treated as the risk factor under study in such analyses, although they vary considerably in complexity depending on the availability of information on other explanatory or confounding variables. The underlying assumption of these studies is that migrants undergo a change in their environment (although the extent of this is rarely documented), so that differences in cancer rates confirm the importance of environmental over genetic determinants of risk. Studies which document risk according to time spent in the new country or to age at migration, or differences between migrants and their offspring, add an extra dimension, interpretable in terms of the degree of lifestyle change, or lability of the cancer to changes in exposure to the relevant determinant. Past studies have frequently used rather simplistic methodology, with insufficient attention to the presence of bias, and a reluctance to use standard epidemiological techniques to control for obvious sources of confounding. Migrant studies are divided into four broad categories, depending on the number of comparison groups (two, or more), the availability of a time dimension, and information on exposures; examples of each are described.


[Cancer in Japanese migrants to Hawaii: interaction between genes and environment]. This paper describes the progressive changes in cancer incidence that have been observed among Japanese after their migration to Hawaii. It reviews descriptive and analytic epidemiologic data suggesting a role for genetic susceptibilities in explaining the high risk of Japanese for colon cancer and their low risk for lung cancer, when compared to Caucasians. Differences in certain pharmacogenetic polymorphisms may explain these risk patterns. This research may lead to a better characterization of cancer risk at the individual level and, consequently, to improved methods of prevention.


Prevention of cutaneous melanoma: an epidemiological evaluation of the Swiss campaign. A national information program, focusing on the main recognized risk factors (primary prevention) and on the potential benefits of early detection (secondary prevention) of cutaneous malignant melanoma, was launched in Switzerland in May 1988. The first campaign, based on a pilot study conducted in 1986 in the canton of Basel, was followed by a recall campaign in July 1989. This report describes the organization of this program and presents an assessment of its initial impact. The number of newly diagnosed cases increased more than twofold (+ 116%) in the two months following the launch of the first campaign (May to June 1988). This trend was accompanied by a statistically significant shift of case distribution towards younger ages (< 60 years; p = 0.003), and a non-significant shift was observed towards less advanced lesions (thickness < or = 1.5 mm). The incidence decreased quickly, though in the twelve month period between the two campaigns it remained 21% higher than before the inception of the program. No appreciable effects were detected from the recall campaign and no difference was seen among regions or between sexes.


[Screening for cardiovascular disease risk factors among employees of a hospital]. A health promotion and screening program for the detection of the major risk factors for ischemic heart disease was carried out in 1990 among the employees (n = 4,521; 70% female) of the Centre Hospitalier Universitaire Vaudois (CHUV). The prevalence of risk factors among the 1,425 employees (73% female) who took part in the study (participation rate: males 29%, females 33%) was compared with the prevalence of risk factors within three other populations: 1) new CHUV employees, who are systematically screened (n = 424: 71% female); 2) a representative sample of the general population; and 3) a group of employees from 44 companies located in the same region. Smoking was the most common of the three main risk factors; its prevalence was lowest among CHUV employees and highest among employees of the 44 firms. The prevalence of hypercholesterolemia and high blood pressure was variable among the different populations. These variations could partly be due to differences in methodologies and measurement conditions, but could not totally be explained in this way.


[Diabetes mellitus and pancreatic cancer: a case-control study in greater Montreal, Quebec, Canada]. In a population-based case-control study of dietary risk factors in French Canadians in Montreal, a total of 179 cases and 239 controls were interviewed between 1984 and 1988. It was found that the frequency of diabetes was almost three times higher in cases of pancreatic cancer (16%) than in the controls (6%), with an Odds Ratio (OR) of 2.52 and a Confidence Interval (CI) of 1.04-6.11. Fifty per cent of the pancreatic cancer cases had this disease before the cancer was diagnosed, compared with 71% of the controls at the time of the study. Those aged 50 years and over accounted for 75% of the cases and 71% of the controls (diabetic subjects); 68% of the cases were treated with a combination of diet and oral hypoglycemic agents compared with 86% of the controls. Insulin was used by 32% of the cases and 14% of the controls. These results suggest that diabetes may play a major role in the etiopathogenesis of pancreatic cancer in this urban population. A lot of controversy remains about the precise role of diabetes, and further studies are needed for a better assessment and understanding of the mechanisms of this association.


[Computer simulation of the 10-year outcome of a cohort of heroin addicts in Ile-de-France]. The aim of this study is to develop a computer simulation model to describe imaginary cohorts of heroin users in the Ile de France (greater Paris) region. Because of the lack of well-designed cohort studies in France, this model is based on epidemiological data found in various different studies. The results of the simulation reveal horrifying outcomes in ten years' time: in the more optimistic scenario (an annual non-Aids mortality rate of 1%, an annual rate of permanent addiction curtailment of 10% and a syringe exchange rate of 10%), only 50% of heroin users curtail their consumption permanently without being HIV carriers after 10 years, 16% are HIV carriers and 10% have died. In conclusion, medical care should play an important part in the management of drug users, and secondary prevention aimed at reducing the health problems involved in heroin use should be intensified.


[Life style of children and obesity in a population of 5-year-old children]. The increasing level of childhood obesity has prompted some research into the early risk factors likely to lead to preventive measures. A case-control study was conducted of a five year-old population in the Rhône and Isère administrative "départements" of France during the children's first visit to primary school, with the participation of 327 obese children and 704 controls. Anthropometric data on the children since birth, together with data on their lifestyles, were collected in interviews with parents. "Family obesity" and "obesity at birth" were found to be closely related to the child's obesity at five years old (adjusted OR = 2.7 and 2.1 respectively). Of the environmental factors, the hypothesis tested paid specific attention to television viewing, snacks between meals and lack of sleep. These three variables were all found to be risk factors of obesity at five years old. However after allowing for parental obesity, the only remaining significant risk factor for obesity at five was lack of sleep (adjusted OR = 1.4). The pathogenic assumptions raised by these results are discussed.