Prevalence of cystic fibrosis mutations in the East German population. A representative multicenter cystic fibrosis (CF) mutation analysis on about half of all known cystic fibrosis patients of the 5 East German Länder is reported. Analyses for 17 mutations, among them Delta F508, R553X, G542X, S549R,N,I, G551D, S1255X, R347P,H, and Y122X, were performed. As expected, the delta F508 mutation in exon 10 of the CFTR gene is the major gene alteration causing CF in our patients. However, in comparison to studies from Western Germany, a significantly lower percentage of just over 60% is found in our patients, resembling data obtained from slavonic populations. The severe phenotype of cystic fibrosis is most frequently associated with homozygosity for the delta F508 mutation. No particular allele association could be found with the intermediate and mild phenotypes of this disease. The next most frequent of the investigated mutations is R553X (13.3% of non-delta F chromosomes) followed by R347P (9.2%) and G542X (4.4%).


Screening for mutations by expressing patient cDNA segments in E. coli: homocystinuria due to cystathionine beta-synthase deficiency. Deficiency of cystathionine beta-synthase (CBS) causes the most common form of inherited homocystinuria. We developed a simple CBS expression system in E. coli to screen for pathogenic mutations in affected individuals. Portions of patient cDNAs were amplified by PCR and used to replace the corresponding segments of normal human CBS cDNA in the bacterial expression plasmid pHCS3. Hybrid CBS was expressed in E. coli and the segments of patient's cDNA which extinguished CBS activity were sequenced to identify the mutation. The first study of a pyridoxine-responsive patient using this screen revealed that of the clones which contained either the middle or the 3'-portion of his cDNA, about half were devoid of catalytic activity. Subsequent sequencing of the affected segments confirmed a compound heterozygosity for a maternal T833-->C transition (I278T) and for a paternal A-->C transversion in the intron 11 splice acceptor. The latter mutation leads to an in-frame deletion of exon 12 (nt 1224-1358, amino acids W408 to G453). This bacterial expression system proved to be a rapid screening method for localizing pathogenic mutations in CBS, allowing us to sequence the affected portions of mutant cDNA within 7-10 days of harvesting cultured fibroblasts.


A novel beta-globin structural mutant, Hb Brescia (beta 114 Leu-Pro), causing a severe beta-thalassemia intermedia phenotype. This study describes a patient with a thalassemia intermedia-like phenotype in whom beta-globin gene sequencing detected a novel abnormal hemoglobin (Hb) due to a T-C substitution at codon 114 of the beta-globin gene arising as a de novo mutation. The abnormal variant was designated Hb Brescia after the place of birth of the propositus. Normal sequences were detected at the in trans beta-globin locus. In addition, alpha-globin gene analysis detected a triple alpha-globin locus which was inherited from the father. The T-C change at position 114 of the beta-globin gene results in a leucine to proline substitution (Leu-Pro) in the G-helix. The resulting Hb tetramer is highly unstable and precipitates forming inclusion bodies in the peripheral red blood cells. Moreover, the Leu-Pro substitution interferes negatively with the four alpha 1 beta 1 contact points of the G-helix most likely adversely affecting the alpha beta dimer formation. The very severe phenotype presented by our patient is unusual in a heterozygote for an unstable Hb variant and may be explained by the coinheritance of the triple alpha-globin locus.


Two missense mutations causing mild hyperphenylalaninemia associated with DNA haplotype 12. The genetic defects responsible for most phenylketonuria (PKU) and hyperphenylalaninemia (HPA) cases are located in the phenylalanine hydroxylase (PAH) gene. Approximately 50-60 mutations have been reported in Caucasians and are reflected in a wide range of clinical severities. Most mutations are linked to specific haplotypes, as defined by eight polymorphic restriction sites in the PAH gene. We hypothesized that there is at least one mild mutation linked to haplotype 12 in the Swedish PKU/HPA population, since 7 of 8 patients carrying haplotype 12 had mild HPA. Sequence analysis revealed a C-to-G transversion at the second base of codon 322, resulting in a substitution of glycine for alanine, in four mutant haplotype 12 genes, and a G-to-A transition at the second base of codon 408, resulting in a substitution of glutamine for arginine, in another three mutant haplotype 12 genes. These mutations segregated with mutant haplotype 12 alleles in nuclear families but were not present on normal or other mutant alleles. Both mutations were tested in a eukaryotic expression system in which enzyme activities of different mutant PAH enzymes reflect the relative severities of the mutations, although these in vitro activities cannot be translated directly into in vivo hepatic activities. The A322G mutant PAH had about 75% and the R408Q mutant PAH about 55% of the wild-type PAH enzyme activity. These in vitro activities are the highest reported for mutant PAH enzymes produced in the same expression system.(ABSTRACT TRUNCATED AT 250 WORDS)


In vitro and in vivo correlations for I65T and M1V mutations at the phenylalanine hydroxylase locus. Mutations at the phenylalanine hydroxylase (PAH) locus are the major cause of hyperphenylalaninemia. We have previously described four mutations (M1V, IVS12nt1, R408W, and S349P) at the PAH locus in French Canadians with ancestry in eastern Quebec. Here we report (1) identification of another mutation, on a haplotype 9 chromosome, which converts codon 65 from isoleucine (ATT) to threonine (ACT), (2) expression analysis of the I65T mutation in COS cells demonstrating 75% loss of both immunoreactive protein and enzyme activity, and (3) expression analysis of the most prevalent PKU allele (M1V) in eastern Quebec, showing nondetectable levels of PAH protein and activity, a finding compatible with a mutation in the translation initiation codon. Homozygosity for M1V and codominant inheritance of I65T/R408W were both associated with classical phenylketonuria.


Illegitimate transcription of phenylalanine hydroxylase for detection of mutations in patients with phenylketonuria. Illegitimately transcribed phenylalanine hydroxylase mRNA was amplified using the polymerase chain reaction from both fibroblasts and Epstein-Barr virus-transformed lymphocytes. This method was used to study mutations of this gene in patients with phenylketonuria and known point mutations were easily detected. Illegitimate transcription was successful for studying splicing defects and it was found that the previously described mutation which changes G to A at the 5' donor site of intron 7 causes exon 7 to be spliced out.


Trapped-oligonucleotide nucleotide incorporation (TONI) assay, a simple method for screening point mutations. We present a simple screening method for detecting a known point mutation, using only one 5'-biotinylated oligonucleotide primer, with its 3' end adjacent to the mutation site. In parallel reactions, an amplified DNA template encompassing the biotinylated oligonucleotide and mutation site undergoes 40 step-cycles of single nucleotide incorporation using Taq thermostable DNA polymerase and only one radioactive [alpha-32P]dNTP, specified by either the normal or mutant sequence. The oligonucleotides, now radioactively labelled at the 3' end according to the template sequence, are then trapped by streptavidin-coated magnetic beads, and the percent of radiolabel incorporated is determined directly by the Cerenkov method in a scintillation counter. The trapped-oligonucleotide nucleotide incorporation (TONI) assay has been used for the screening of a mitochondrial polymorphism, and has also been shown to distinguish the genotypes of hemoglobin A/C, A/A, A/S, and S/S. It is reproducible over at least a 100-fold range of radioisotope and a 10-fold range of oligonucleotide primer. This method is particularly useful for diagnosing mutations which do not produce alterations detectable by restriction enzyme analysis, since optimization of conditions is rarely necessary. In addition, it requires only a single oligonucleotide, and no electrophoretic separation of the allele-specific products. It thus represents an improved and simplified modification of the existing allele-specific primer extension methods (Kuppuswamy et al., Proc Natl Acad Sci USA 88:1143-1147, 1991; Sokolov, Nucl Acids Res 18:3671, 1989; Syvanen et al., Genomics 8:684-692, 1990).


Mutations and polymorphisms in the pyruvate dehydrogenase E1 alpha gene. We present an update on mutations and polymorphisms in the human X chromosome located pyruvate dehydrogenase E1 alpha gene. A total of 20 different mutations are tabulated. The mutations include deletions, insertions, and point mutations. Certain sequences seem particularly prone to mutation. Most of the mutations are found in exons 10 and 11. Furthermore, four of the mutations are seen in unrelated patients. Little is known about how the mutations affect the structure or function of the pyruvate dehydrogenase complex.


Plant endogenous beta-glucuronidase activity: how to avoid interference with the use of the E. coli beta-glucuronidase as a reporter gene in transgenic plants. We have detected a plant beta-glucuronidase activity, present in several tissues and organs of plant species belonging to different families. The fluorimetric beta-glucuronidase assay was used to partially characterize this activity in post-ribosomal supernatants of tobacco leaves. The tobacco activity is very stable at low temperatures, but quickly inactivated above 45 degrees C. It is relatively resistant to proteases and insensitive to -SH group reagents and to ionic conditions. It does not require, nor is it inhibited by, divalent cations. Although these properties are shared by the Escherichia coli beta-glucuronidase, the two activities can be distinguished by: (i) their different sensitivity to the specific inhibitor saccharic acid-1,4-lactone; (ii) their different thermal stability (iii) their different pH optima (5.0 for the plant activity and close to neutral for the bacterial enzyme). Therefore, under appropriate experimental conditions, it should be possible to assay the E. coli beta-glucuronidase in transgenic plants without interference from the endogenous plant activity.


Coexpression of the cys E and cys M genes of Salmonella typhimurium in mammalian cells: a step towards establishing cysteine biosynthesis in sheep by transgenesis. The Salmonella typhimurium genes for serine acetyltransferase (cys E) and O-acetylserine sulphydrylase B (cys M) were isolated and characterized in order to express these as transgenes in sheep to establish a cysteine biosynthesis pathway and, thereby, to achieve an increased rate of wool growth. Comparison of the S. typhimurium and Escherichia coli genes showed considerable homology, both at the nucleotide and amino acid sequence levels. The in vitro and in vivo expression studies showed that both genes could be transcribed and translated in eukaryotic cells and that their products could function as active enzymes. The cys M gene of S. typhimurium possessed a GUG initiation codon, like its E. coli counterpart, but translation could be initiated using this codon in eukaryotic cells to give an active enzyme product. Chinese hamster ovary cells, stably transfected with a tandem arrangement of the two genes, showed a capacity to synthesize cysteine in vivo, indicating the establishment of a cysteine biosynthesis pathway in these cells. The measured levels of activity of the gene products suggest that improved wool growth is possible by transgenesis of sheep with these genes.


High level expression of human apolipoprotein A-I in transgenic rats raises total serum high density lipoprotein cholesterol and lowers rat apolipoprotein A-I. To examine the consequences of increased apolipoprotein A-I production on cholesterol and lipoprotein metabolism, we have produced two lines of transgenic rats; one expressing moderate and one very high levels of human apolipoprotein A-I. The rats were produced by microinjection of a 13 kbp DNA fragment containing the human apolipoprotein A-I gene plus 10 kbp of its 5' flanking sequence and 1 kbp of its 3' flanking sequence. Both lines of transgenic rats express human apolipoprotein A-I mRNA in liver and human apolipoprotein A-I in plasma. Sera from these rats contain significantly higher levels of total apolipoprotein A-I, high density lipoprotein cholesterol and phospholipid than sera from non-transgenic littermates. Transgenic rats expressing high levels of human apolipoprotein A-I have reduced levels of serum rat apolipoprotein A-I suggesting a mechanism exists to down-regulate apolipoprotein A-I production. These transgenic rats provide a unique animal model to examine the effects of increased apolipoprotein A-I production on lipid and lipoprotein metabolism.


Impaired expression of chimaeric major histocompatibility complex transgenes associated with plasmid sequences. Plasmid vector sequences were retained (vector+), or removed (vector-) from hybrid major histocompatibility complex gene constructs prior to microinjection of fertilized ova for the production of transgenic mice. In transgenic mice containing integrated vector+ gene constructs, low levels of class II cell surface determinants were detected on splenocytes from only two out of six independent lines. Class II membrane determinants were not detectable on splenocytes from the remaining four vector+ transgenic lines. Expression of transgene products did not correlate with transgene copy number which ranged from 1-10 copies. Low levels of mRNA transcripts were detected in thymic mRNA from vector+ lines. In contrast, high levels of thymic and splenic mRNA transcripts were detected in offspring from all four vector- transgenic lines. Spleen cells from the vector- transgenic animals also expressed high levels of the hybrid major histocompatibility complex transgene products. These results implicate plasmid vector sequences in the inhibition of expression of the hybrid class II-class I major histocompatibility complex genes in transgenic mice. This putative inhibition of transgene expression presumably occurs at the level of gene transcription.


Pollen-specific expression of the Arabidopsis thaliana alpha 1-tubulin promoter assayed by beta-glucuronidase, chloramphenicol acetyltransferase and diphtheria toxin reporter genes. We have characterized the promoter specificity of the Arabidopsis thaliana alpha 1-tubulin (alpha 1-tub) gene by studying expression patterns of gene fusions between the 2.2 kbp 5' upstream region of the alpha 1-tub gene and each of three different reporters: chloramphenical acetyltransferase, beta-glucuronidase or the diphtheria toxin chain A gene. Analysis of transgenic tobacco and Arabidopsis plants carrying the transgene showed that the chloramphenicol acetyltransferase and beta-glucuronidase activities were not detected in any vegetative or reproductive organs except mature pollen. Transgenic tobacco plants carrying the diphtheria toxin chain A gene under the control of the alpha 1-tub promoter were of normal phenotype but seed fertility was drastically reduced. Furthermore, the transgene could not be transmitted to the next generation through pollen, supporting the observation that the alpha 1-tub promoter is active only in pollen. It was observed that the promoter activity was most active in mature pollen and decreased significantly during in vitro pollen germination, indicating that the promoter is inactive or subdued in germinating pollen. The promoter activity was not affected by various plant growth hormones during pollen maturation.


Somatotropic and lactotropic receptors in transgenic mice expressing human or bovine growth hormone genes. The somatotropic and lactotropic receptors were studied in liver microsomal preparations from transgenic mice carrying the human growth hormone (hGH) or bovine growth hormone (bGH) gene fused to mouse metallothionein-I (MT) or phosphoenolpyruvate carboxykinase promoter/regulator (PEPCK). Specificity studies indicated that, similarly to normal mice, liver microsomes from the transgenic animals possess a mixed population of somatotropic and lactotropic binding sites. In transgenic animals of both sexes, the binding capacity of somatotropic receptors was significantly increased without corresponding changes in affinity. Expression of the MT-hGH hybrid gene was associated with the induction of somatotropic receptors which was approximately twice as great as that measured in animals expressing the MT-bGH hybrid gene. The binding capacity of lactotropic receptors in liver microsomes (quantitated by the use of labelled ovine prolactin) was increased 2-3 fold in transgenic females and approximately 10-fold in transgenic males as compared to the respective normal controls. We conclude that lifelong excess of GH up-regulates hepatic GH and prolactin receptors, and that lactogenic activity of GH is not essential for induction of prolactin receptors in the liver of transgenic mice.


Synthetic cryIIIA gene from Bacillus thuringiensis improved for high expression in plants. A 1974 bp synthetic gene was constructed from chemically synthesized oligonucleotides in order to improve transgenic protein expression of the cryIIIA gene from Bacillus thuringiensis var. tenebrionis in transgenic tobacco. The crystal toxin genes (cry) from B. thuringiensis are difficult to express in plants even when under the control of efficient plant regulatory sequences. We identified and eliminated five classes of sequence found throughout the cryIIIA gene that mimic eukaryotic processing signals and which may be responsible for the low levels of transcription and translation. Furthermore, the GC content of the gene was raised from 36% to 49% and the codon usage was changed to be more plant-like. When the synthetic gene was placed behind the cauliflower mosaic virus 35S promoter and the alfalfa mosaic virus translational enhancer, up to 0.6% of the total protein in transgenic tobacco plants was cryIIIA as measured from immunoblot analysis. Bioassay data using potato beetle larvae confirmed this estimate.


Biosafety of kanamycin-resistant transgenic plants. Kanamycin resistance is one of the most frequently used selection markers for obtaining transgenic plants. The introduction of these transgenic plants into agricultural practice will cause the kanamycin resistance gene and the gene product to be present on a large scale. The desirability of this situation is analysed. The nature, properties and applications of the antibiotic kanamycin are briefly reviewed, as are the mechanisms of kanamycin resistance. It is argued that the gene used for resistance is an excellent choice because of the high substrate specificity of the enzyme encoded. Human or veterinary antibiotic therapies will not be compromised. Also, the physico-chemical characteristics of the antibiotic exclude the existence of selective conditions in the environment. Therefore, a transgenic plant or any other organism that might have acquired the gene will not get any selective advantage because of this gene. Evidence further suggests there is no toxicity or predictable harm of both gene or gene product for human or animal consumption. Full legislative clearance of this transgenic trait is therefore acceptable.


Tissue partitioning of cadmium in transgenic tobacco seedlings and field grown plants expressing the mouse metallothionein I gene. Since agricultural crops contribute > 70% of human cadmium (Cd) intake, modification of crops to reduce accumulation of this pollutant metal during plant growth is desirable. Here we describe Cd accumulation characteristics of seedlings and field grown tobacco plants expressing the Cd-chelating protein, mouse metallothionein I. The objective of the transformation is to entrap Cd in roots as Cd-metallothionein and thereby reduce its accumulation in the shoot. Transformed and control seedlings were exposed for 15 days in liquid culture at a field soil-solution-like Cd concentration of 0.02 microM. Transformed seedlings of Nicotiana tabacum cultivar KY 14 contained about 24% lower Cd concentration in shoots and about 5% higher Cd concentration in roots than control seedlings. Dry weights of transformed and control tissues did not differ significantly. In the field in 1990, mature transformed N. tabacum cv. KY 14 plants exposed only to endogenous soil Cd contained about 14% lower leaf lamina Cd concentration than did controls. Differences were significant at the p < or = 0.1 level in 13 of 16 leaf positions. Leaf dry weight did not differ significantly but transformed field plants had 12% fewer leaves and were 9% shorter than the controls. Copper (Cu) concentration was significantly higher (ca10%) in the bottom nine leaf positions of transformed plants suggesting that reduced leaf number and plant height may be due to Cu deficiency or toxicity. Alternatively, somaclonal variation or gene position effects may be involved. No differences were found in zinc levels. With N. tabacum cv. Petit Havana, transformed seedlings contained no less Cd in shoots but 48% higher Cd concentration in roots.(ABSTRACT TRUNCATED AT 250 WORDS)


[Normal sexual differentiation: molecular genetic and endocrinology]. Analysis of the sexual determination and differentiation factors has progressed by the important findings made in biochemistry (hormonal assays, determination of the receptor concentration), in cellular and molecular endocrinology (mechanism of the hormonal action) and in genetics (identification, isolation and cloning of the genes implied in the sexual determination and differentiation pathways). We first describe the basis of sexual determination and differentiation, and then we analyze the different roles of SRY gene, encoding for the testis determining factor, androgen receptor gene, 5 alpha-reductase gene and anti-Müllerian hormone gene.


[Chronic cardiac insufficiency, a disease of adaptation]. Cardiac hypertrophy due to a mechanical overload is not a disease per se but the physiological reaction of the heart to a disease which is usually arterial hypertension and/or coronary insufficiency. It results from the put into play of several changes in gene expression, frequently species-specific, which explain the thermodynamic improvement of the cardiac function and the physiological adaptation of the heart to the new environmental requirements. Some of these modifications can have detrimental consequences and explain the modifications of ventricular compliance and the high incidence of arrhythmias in ventricular hypertrophy. The most important changes in the genetic expression which have been reported so far after pressure overload are located on contractile proteins and on membrane proteins.


Gallstones and laparoscopic cholecystectomy. The National Institutes of Health Consensus Development Conference on Gallstones and Laparoscopic Cholecystectomy brought together surgeons, endoscopists, hepatologists, gastroenterologists, internists, radiologists, and epidemiologists as well as other health care professionals and the public to address (1) the indications for treatment of patients with gallstones; (2) the role of laparoscopic cholecystectomy in treating patients with gallstones; (3) the role of alternative medical and surgical treatments for gallstones; (4) the comparative results of laparoscopic cholecystectomy with open cholecystectomy and other available treatments; (5) techniques for detecting and treating bile duct stones with or without laparoscopic cholecystectomy; and (6) future directions for research in prevention and management of gallstone disease and in laparoscopic cholecystectomy. Following 2 days of presentations by experts and extensive discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the panel concluded that (1) most patients who experience symptoms of gallstones should be treated; (2) in comparison with open cholecystectomy, laparoscopic cholecystectomy provides a safe and effective treatment for most patients with symptomatic gallstones and has become the treatment of choice for many patients; (3) patients who are not good candidates for laparoscopic cholecystectomy include those with generalized peritonitis, septic shock from cholangitis, severe acute pancreatitis, endstage cirrhosis, and gallbladder cancer; (4) laparoscopic cholecystectomy decreases pain and disability without increasing mortality and morbidity and can be performed at an equal or lower cost than open cholecystectomy; and (5) every effort should be made to ensure that surgeons performing laparoscopic cholecystectomy are properly trained and credentialed. The full text of the consensus panel's statement follows.


[Elastin and arteriosclerosis: determination and characterization of elastin peptides in blood]. During pathologies such as arteriosclerosis and emphysema, degradation of elastin by elastases occurs and elastin peptides are produced. In order to evaluate elastin degradation, measurements of elastin peptide concentration in human blood were carried out. According to elastin peptides used for obtention of antibodies and for ELISA, the measured values are different. Elastin peptides have several biological effects: they are chemotactic, modify ion fluxes and several intracellular mechanisms.


[Molecular pathology of Duchenne and Becker muscular dystrophy]. Duchenne and Becker muscular dystrophies (DMD and BMD) are two allelic recessive X-linked disorders. Molecular deletions of various regions of the dystrophin gene are the main mutations detected in DMD and BMD patients. Molecular study of DMD and BMD DNA are instrumental to understand the pathological molecular mechanisms and the function of the protein. We describe here dystrophin and its interaction with a glycoprotein complex and we then focus on two particular patients with partial deletions of the dystrophin gene: 1) a typical Becker patient, who shows an intragenic deletion disrupting the reading frame. We describe in this case alternative splicings restoring the reading frame, which might explain the mild clinical phenotype of this patient, 2) a deletion of the distal part of the DMD gene coding for the carboxyterminal domain of the dystrophin in a young patient. The normal localization of dystrophin at the inner face of the plasma membrane in the muscle of this patient suggests that the last domain of this protein is not sufficient to anchor dystrophin at the membrane.


[Molecular genetics of growth hormone resistance syndrome]. The cloning of a putative growth hormone receptor (GH-R) cDNA has opened new approaches for the understanding of the molecular basis of GH insensitivity in humans. This molecule belongs to a new class of transmembrane receptors including prolactin, granulocyte-macrophage colony stimulating factor, erythropoietin and some interleukin receptors. Although the domains responsible for signal transduction have not yet been identified, the molecular study of a GH-resistance syndrome described by Laron et al. should provide insight into the structure-function relationships of the GH-R and related receptors. This autosomal recessive disorder is characterized by very low serum levels of Insulin-Like Growth Factor I (IGF-I), despite increased secretion of GH with normal activity. Two approaches can be used to test the involvement of the GH-R in this syndrome. The first one, which is indirect, is performed through linkage analysis between GH-R and Laron phenotype; this allowed us to incriminate the GR-R gene in this syndrome. The second approach consists in the identification of molecular defects in the GH-R gene of patients with Laron syndrome; this allowed the detection of a partial gene deletion and different point mutations. The short stature of the Pygmee population could be related to the Laron syndrome because individuals from this population are also resistant to GH therapy. Therefore, it seems interesting to search for molecular variations of the GH-R gene in this population. Nevertheless, preliminary results indicate that the GH-R gene is not directly involved in this particular short stature condition.(ABSTRACT TRUNCATED AT 250 WORDS)


[Pathology of unstable sequence of genome: fragile-X-syndrome]. Fragile X syndrome is the most frequent form of inherited mental retardation and is associated with a fragile site at Xq27-3. This fragile site is an unstable microsatellite repeat, p(CCG). In fragile X syndrome families, this sequence exhibits variable amplification, the length of which correlates with phenotype. Affected persons have both a "full mutation" and abnormal DNA methylation. Subjects with smaller increase of this sequence, called "premutation", have little or no risk retardation, but are at high risk of having affected children or grandchildren. The passage from "premutation" to "full mutation" status occurs only with transmission from the mother. The unusual segregation patterns in fragile X pedigrees is referred to as the Sherman paradox, now elucidated by genotypic analysis. We present here a brief review of this pathology and illustrate the use of this new diagnostic test in our laboratory.


[Illegitimate transcription: discovery and application to gene molecular pathology]. In 1988, by using the powerful cDNA/PCR technique, it was demonstrated that there are very low levels of dystrophin mRNA in a variety of non-muscle tissues, including cultured fibroblasts and lymphoblastoid cell lines. The phenomenon was also shown for a number of other tissue-specific gene, including beta-globin, factors VIIIc and IX, anti-müllerian hormone, L-pyruvate kinase, retinal blue pigment, phenylalanine hydroxylase. The level of transcript in inappropriate cells is exceedingly low, perhaps one mRNA per 100-1,000 cells. This low-level ubiquitous transcription of tissue-specific genes was called "illegitimate" or "ectopic" transcription, and has been proven to occur for 17 gene transcripts to date. The mechanism and biological significance of illegitimate transcription are still obscure, but, since illegitimate transcripts exhibit the same pathology as legitimate transcripts, they have been useful tool in the study of already 9 inherited diseases. This strategy will be applied widely for diseases where samples from the appropriate tissue for study is difficult to obtain, or where an mRNA is easier or more informative to study than a genomic DNA (as for large genes, or where alternative splicings is involved).


[Cytotoxic response against human immunodeficiency virus (HIV): control with suppressor factor]. We report a new suppressor function of CD8+ CD57+ lymphocytes from HIV-seropositive patients recipients, on the cytolytic activity of allospecific CTL, NK and LAK cells. This inhibitory effect is mediated by a non-antigen specific soluble factor distinct from PGE2, TGF beta and TNF alpha and beta. Biochemical characterization indicates that the CD8+ CD57+ inhibitory activity: 1) is heat and trypsin resistant but remains sensitive to pronase E hydrolyse, 2) specifically bind to concanavalin A-sepharose column, 3) is mediated by a 20-30 kdaltons glycoprotein.


[In vivo and in vitro antitumoral effects of an extract from Vibrio cholerae in different murine models. I. Effect in vivo of bacterial extract from Vibrio cholerae on the development of different murine tumoral grafts]. A bacterial extract from Vibrio cholerae, so called DGZ, is shown to prevent transplantation of sarcoma 180 and Lewis lung carcinoma. A 4 days DGZ treatment (4 x 100 micrograms) triggers reject of the graft by 40% of the mice. The mice which have rejected a graft once after treatment, cannot be grafted lately or, at least, the tumor growth is delayed. The association with cisplatinum (4 x 25 micrograms) allows to protect 90 to 95% of the mice.


[Development of a technique for the complete correction of transposition of great vessels]. Complete transposition of the great arteries is one of the most common cardiovascular anomalies. Several surgical methods of treatment have been proposed. Arterial repair theoretically seems a better option since it does not introduce any additional intra cardiac anomaly and it restores the left ventricle to its natival systemic function. The rationale for neonatal arterial repair lies on fetal and neonatal cardiopulmonary physiology. The left ventricle has to eject immediately after surgery a normal cardiac output at systemic pressure in the aorta. This is the case in the neonatal period, because during fetal life pulmonary artery and aortic pressure are equal. For simple TGA, after birth, with the fall in pulmonary vascular resistances and constriction of the ductus arteriosus, pulmonary artery and left ventricular pressures drop dramatically to less than one third (1/3) of systemic pressure. As a result, the left ventricle is not stimulated for growth adaptation and becomes a thin ventricle less contractile and more compliant. However, there is little doubt that during the first 2 to 4 post-natal weeks, the left ventricle is still suitable to sustain a systemic workload. Between april 1984 and april 1992, four hundred and twenty six (426) consecutive neonates underwent an arterial switch operation for various forms of transposition: with 34 hospital deaths. The mean age at operation was 13 days and the mean weight was 3.2 kg. Among patients with TGA-VSD and coarctation, 14 underwent a single stage repair through mid sternotomy. Actuarial survival rates were: 89% for TGA-IVS at 5 years, 90% for TGA-VSD, 85.3% for TGA-VSD and coarctation at 3 years.(ABSTRACT TRUNCATED AT 250 WORDS)


[HDL and reverse cholesterol transport. Role of cholesterol ester transfer protein]. As most of peripheral cells are not able to catabolize cholesterol, the transport of cholesterol excess from peripheral tissues back to the liver, namely "reverse cholesterol transport", is the only way by which cholesterol homeostasis is maintained in vivo. Reverse cholesterol transport pathway can be divided in three major steps: 1) uptake of cellular cholesterol by the high density lipoproteins (HDL), 2) esterification of HDL cholesterol by the lecithin: cholesterol acyltransferase and 3) captation of HDL cholesteryl esters by the liver where cholesterol can be metabolized and excreted in the bile. In several species, including man, cholesteryl esters in HDL can also follow an alternative pathway which consists in their transfer from HDL to very low density (VLDL) and low density (LDL) lipoproteins. The transfer of cholesteryl esters to LDL, catalyzed by the Cholesteryl Ester Transfer Protein (CETP), might affect either favorably or unfavorably the reverse cholesterol transport pathway, depending on whether LDL are finally taken up by the liver or by peripheral tissues, respectively. In order to understand precisely the implication of CETP in reverse cholesterol transport, it is essential to determine its role in HDL metabolism, to know the potential regulation of its activity and to identify the mechanism by which it interacts with lipoprotein substrates. Results from recent studies have demonstrated that CETP can promote the size redistribution of HDL particles. This may be an important process in the reverse cholesterol transport pathway as HDL particles with various sizes have been shown to differ in their ability to promote cholesterol efflux from peripheral cells and to interact with lecithin: cholesterol acyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)


Blood pressure and heart rate response to vasoactive agents in conscious diabetic rats. Blood pressure and heart rate responses to different vasoactive agents were observed in conscious streptozotocin-diabetic rats. An indwelling femoral artery catheter was used for direct measurement of arterial pressure and heart rate. The femoral vein was cannulated for drug administration. In a resting state diabetic rats showed lower heart rates and lower systolic blood pressure. The vasodepressor response to both acetylcholine and sodium nitroprusside was decreased, while the heart rate increase induced by the baroreceptor reflex was not altered. Both the increase in blood pressure and the reflex bradycardia to norepinephrine were decreased in the diabetic group. When the change in heart rate was plotted against blood pressure in response to norepinephrine, there was no difference in the two groups of animals. The vasodepressor response to isoproterenol, hydralazine, and verapamil in diabetic rats was unchanged. The results demonstrate a decreased vascular responsiveness in diabetic rats to norepinephrine, acetylcholine, and nitroprusside. The diabetes-induced vascular system changes require further study to understand the mechanisms involved.


Hemodynamic and plasma atrial natriuretic factor responses to cardiac volume loading in young versus older normotensive humans. To assess the effects of age on responsiveness of atrial natriuretic factor (ANF) release, and the possible contribution of cardiac sympathetic activity, in young (n = 8) and older normotensives (n = 7), the effects of cardiac volume load on plasma ANF, central venous pressure, and general hemodynamics were evaluated. Studies were performed after pretreatment with placebo or 80 mg propranolol. Cardiac volume loading increased central venous pressure by 3-5 mmHg (1 mmHg = 133.3 Pa); beta-blockade did not affect this response. Cardiac volume load caused significant increases in heart rate (10-15 beats/min) and cardiac index (by 0.7-0.8 L.min-1.m-2) and decreases in plasma catecholamines. Propranolol attenuated the increases in heart rate and cardiac index. These hemodynamic responses did not differ significantly between the two groups of subjects. Cardiac volume load significantly increased plasma ANF, by 87 +/- 21 pg/mL in the young normotensives and by 212 +/- 33 pg/mL in the older normotensives (p < 0.01, young vs. older). beta-Blockade did not affect this different response. Our results show that the plasma ANF response to volume loading is potentiated by aging. Although differences in atrial stretch cannot be excluded, this effect may relate to the decrease in clearance of plasma ANF occurring with aging.


Modification of the renal response to endopeptidase inhibition and atrial natriuretic peptide infusion in normal dogs. Inhibition of intrarenal neutral endopeptidase 24:11 (NEP) increases the natriuretic response to infused atrial natriuretic peptide (ANP). In various models of canine heart failure, angiotensin and kinins have been shown to modulate ANP and (or) NEP activity. In the present study, we examined possible modulators of NEP activity in normal dogs by infusing various agents into the left renal artery (or by denervating the left kidney) and comparing the response of this kidney with that of the contralateral one following the combined intravenous infusion of Squibb 28603 (a potent NEP inhibitor) and ANP (75 ng.kg-1.min-1). Four dogs received angiotensin (1.5 ng.kg-1.min-1) into the left renal artery, 8 dogs received saralasin (5 micrograms/min), 5 dogs received noradrenaline (2 micrograms/min), and 6 dogs received bradykinin (3 micrograms/min). Five dogs underwent left renal denervation. Angiotensin inhibited sodium excretion following the NEP inhibitor alone and after the NEP inhibitor plus ANP. Saralasin augmented the natriuretic response. None of the other protocols influenced sodium excretion. We conclude that angiotensin may modulate either the enzymatic degradation of ANP or influence its renal tubular effects.


Changes in blood flow distribution during the perinatal period in fetal sheep and lambs. We have measured total blood flows and blood flows per 100 g tissue to major tissues at 120 and 140 days gestation in fetal sheep and at 3 and 21 days of age in lambs (gestation period = 144 +/- 2 days). Between 120 and 140 days gestation, flow per 100 g tissue increased by 74, 150, and 317% in the renal, intestinal, and hepatic arterial beds, but no further significant change in flow was observed at 3 or 21 days postpartum. Blood flows per 100 g to cerebral hemispheres and cerebellar tissues also increased dramatically during late gestation (142 and 121%, respectively), but declined sharply by 3 days postpartum (73 and 75%, respectively). Brain blood flows at 21 days postpartum remained substantially below late gestational levels. Adrenal blood flows per 100 g more than doubled during late gestation, fell by more than half at birth, and only partially recovered by 21 days of age. Blood flows to carcass tissues did not change in late gestation, fell at birth, then partially recovered. Pre- and post-natal increases in brain blood flows were almost entirely attributable to increased perfusion rather than tissue growth, whereas large perinatal increases in flow to the diaphragm paralleled tissue growth. Tissue growth and increased perfusion per 100 g contributed almost equally to increased blood flows to kidneys postnatally, and to adrenal glands and the gastrointestinal tract prenatally.


Calcitonin gene related peptide relaxes cholecystokinin-induced contraction in guinea pig gallbladder strips in vitro. Calcitonin gene related peptide has been shown to relax vascular and intestinal smooth muscle. This study examines the effects of calcitonin gene related peptide on cholecystokinin-induced contraction of guinea pig gallbladder strips in vitro. Calcitonin gene related peptide was found to cause a dose-dependent relaxation of cholecystokinin-induced tension, which was blocked by the calcitonin gene related peptide receptor antagonist human calcitonin gene related peptide. Previous studies demonstrated that calcitonin gene related peptide acted directly on guinea pig gallbladder smooth muscle to inhibit acetylcholine- or KCl-induced contraction. The present results further confirm that calcitonin gene related peptide acts directly on the smooth muscle. In addition, the use of L-NG-nitroarginine methyl ester, glibenclamide, and other agents strongly suggests that calcitonin gene related peptide also acts by way of the nonadrenergic noncholinergic nervous system, to induce the relaxation of cholecystokinin-induced contraction observed in the guinea pig gallbladder strips.


Effects of fructose loading in streptozotocin-diabetic and nondiabetic rats. The present study compares the cardiovascular consequences of a 6-week fructose feeding in nondiabetic and streptozotocin-diabetic rats. Myocardial performance of these animals was determined using the isolated perfused working heart preparation. Systolic blood pressure, pulse rate, ventricular weight/body weight ratio, and plasma levels of glucose, insulin, triglycerides, and cholesterol were measured. In nondiabetic rats, fructose drinking caused significant increases in blood pressure, pulse rate, and plasma concentrations of insulin and triglycerides. Streptozotocin-diabetic animals exhibited significantly less body weight growth, slower pulse rate, higher plasma levels of cholesterol and triglycerides, ventricular enlargement, and functional impairment of the myocardium. The fructose-loaded diabetic rats had larger increases in plasma cholesterol and triglycerides than did control fructose-fed rats, but the fructose-induced increases in blood pressure and pulse rate were attenuated significantly. However, plasma levels of glucose and insulin and the degree of ventricular enlargement and myocardial dysfunction were not significantly different from those of control diabetic rats. These results show that fructose loading for 6 weeks can cause increases in blood pressure, pulse rate, and plasma lipids in both nondiabetic and diabetic rats. However, fructose ingestion does not significantly alter glycemic control or affect the development of myocardial dysfunction in streptozotocin-diabetic rats.


Interleukin-1 receptor antagonist: effectiveness against interleukin-1 fever. Conscious cats were used to examine the effectiveness of the interleukin-1 receptor antagonist against the fever induced by interleukin-1 and endotoxin. Although inactive by itself, the antagonist (three 1-micrograms bolus injections at 10-min intervals), injected into the third ventricle, attenuated the febrile response to a subsequent intracerebroventricular bolus of interleukin-1. The rise in prostaglandin E2 levels in cerebrospinal fluid, which is a characteristic feature of fever, was curtailed as well. The interleukin-1 antagonist had little or no inhibitory effect on the response to an intracerebroventricular bolus of endotoxin, even though a higher dose was employed (2-micrograms bolus injections given three times at 10-min intervals and six times at 30-min intervals, respectively, before and after endotoxin administration). At either dosage, the intracerebroventricular antagonist was completely ineffective against an intravenous bolus injection of interleukin-1 or endotoxin and both fever and prostaglandin E2 elevation developed unabated. We conclude that brain receptors mediating the pyrogenic action of centrally injected interleukin-1 are susceptible to the antagonist. The same receptors, however, are seemingly not activated by systemic pyrogens. Our findings are consistent with the concept of circulating interleukin-1 acting outside the blood-brain barrier in the normal sequence of fever.


Serotonin (5-HT2) receptor mediated enhancement of cortical unit activity. Simultaneous single-unit and intracortical activity were recorded from neocortical neurons in urethane-anaesthetized rats to investigate the role of serotonin (5-HT) in modifying cortical excitability. Units, at a depth of 775-1100 microns from the pial surface, discharged in a burst-pause pattern that was correlated with slow wave activity. Application of noxious somatic stimulation resulted in cortical desynchronization and altered the pattern of unit activity such that firing was continuous, i.e., the pauses were eliminated. Intravenous administration of the mixed 5-HT1C/5-HT2 antagonists (cinanserin, cyproheptadine, ketanserin, and ritanserin) prevented both desynchronization and the change in unit activity induced by noxious stimulation within 2.5-15 min of the injection. The basic pattern of burst-pause activity remained intact, but the number of spikes per burst was typically reduced, whereas interburst intervals were increased. Iontophoretic application of these antagonists onto cortical neurons resulted in actions similar to those observed following systemic administration. Intravenous and iontophoretic application of m-trifluomethylphenylpiperazine (5-HT1C agonist, 5-HT2 antagonist) resulted in actions indistinguishable from those observed with the above antagonists, from which we conclude 5-HT2 and not 5-HT1C receptors mediate the alteration in unit activity observed with noxious stimulation. The results are discussed with respect to an interaction between N-methyl-D-aspartate and 5-HT2 receptors leading to the enhanced unit activity observed with noxious stimulation.


Dose-dependent, mechanism-based inactivation of cytochrome P450 monooxygenases in vivo by 1-aminobenzotriazole in liver, lung, and kidney of untreated, phenobarbital-treated, and beta-naphthoflavone-treated guinea pigs. The mechanism-based inactivation of the cytochrome P450 (P450) dependent monooxygenase system was studied in vivo in liver, lung, and kidney of untreated, phenobarbital-treated, and beta-naphthoflavone-treated guinea pigs 24 h after administration of 1-aminobenzotriazole (1-100 mg/kg, i.p.). Microsomal isozyme-selective or -specific monooxygenase activities were inhibited in a dose-dependent manner in all three organs. In the liver of untreated and phenobarbital-treated animals, 7-pentoxyresorufin O-depentylation (catalyzed primarily by P450 2Bx, an orthologue of rabbit P450 2B4/rat 2B1) was inhibited more than 7-ethoxyresorufin O-deethylation (P450 1A1), 4-aminobiphenyl N-hydroxylation (P450 1A2), erythromycin N-demethylation (P450 3A), or benzphetamine N-demethylation; in beta-naphthoflavone-treated animals, 4-amino-biphenyl N-hydroxylation activity was preferentially inhibited. In lung, the order of inactivation of monooxygenase activities was 4-aminobiphenyl N-hydroxylation (4Bx, the orthologue of rabbit 4B1) > 7-pentoxyresorufin O-depentylation activity (2Bx) > 7-ethoxyresorufin O-deethylation (1A1; for example 72, 53, and 29% inactivation, respectively, in phenobarbital-treated animals at 100 mg/kg). In all three tissues the loss in spectrally assayed P450 content corresponds quite well to the inhibition of monooxygenase activities. Thus, these studies show that 1-aminobenzotriazole is an effective inactivator of the pulmonary, hepatic, and renal P450 systems in guinea pigs following i.p. administration, and that P450 1A2 (liver) and P450 4Bx (lung), isozymes efficient for the oxidation of primary aromatic amines, are preferentially inactivated.


Enhanced chronotropic and inotropic responses of rat myocardium to cholinergic stimulus with aging. The ability of the heart to respond to adrenergic stimulation diminishes with aging, and this may be one of the factors contributing to the age-associated decline in cardiac stress responsiveness. On the other hand, little is known about the impact of aging on the responsiveness of the heart to cholinergic stimulation. In this study, we determined the chronotropic and inotropic responses of the isolated, Langendorff-perfused hearts from adult (6-8 months) and aged (28-30 months) rats to cholinergic agonists so as to assess age-related alterations in postsynaptic cholinergic control of heart function. The results showed the following. (i) In isolated perfused spontaneously bearing rat hearts, the negative chronotropic response to acetylcholine (10(-9)-10(-5) M) was up to 4-fold greater in the aged compared with adult hearts; this age-related difference was less marked (2-fold) but not abolished in the presence of a maximally effective concentration (5 microM) of the cholinesterase inhibitor eserine. (ii) The cholinesterase-resistant agonist carbachol (10(-9)-2.5 x 10(-6) M) elicited a 2- to 3-fold greater negative chronotropic response in the aged compared with adult hearts. (iii) In isolated perfused, electrically paced (4 Hz) rat hearts, carbachol (10(-9)-10(-5) M) elicited a concentration-dependent negative inotropic response, which was 2-fold greater in the aged compared with adult heart at all carbachol concentrations. (iv) Acetylcholinesterase activities (micromoles per gram per hour) were 50-60% lower in the aged atria (83 +/- 21) and ventricles (24 +/- 6) than in adult atria (210 +/- 20) and ventricles (47 +/- 7).(ABSTRACT TRUNCATED AT 250 WORDS)


Erythrocyte ion regulation across inactive muscle during leg exercise. Ion concentration changes in whole blood, plasma, and erythrocytes across inactive muscle were examined in eight healthy males performing four 30-s bouts of maximal isokinetic cycling with 4 min rest between each bout. Blood was sampled from the arm brachial artery and deep antecubital vein during the intermittent exercise period and for 90 min of recovery. Arterial and venous erythrocyte lactate concentration ([Lac-]) increased from 0.3 +/- 0.1 to 12.5 +/- 1.3 (p < 0.01) and 1.1 +/- 0.4 to 8.5 +/- 1.5 mmol/L (p < 0.01), respectively, returning to control values during recovery. Arterial and venous plasma [Lac-] increased from 1.5 +/- 0.2 to 27.7 +/- 1.8 and from 1.3 +/- 0.4 to 25.7 +/- 3.5 mmol/L, respectively, and was greater than erythrocyte [Lac-] throughout exercise and recovery. Arterial and venous [K+] increased in erythrocytes from 119.5 +/- 5.1 to 125.4 +/- 4.6 (p < 0.01) and from 113.6 +/- 1.7 to 120.6 +/- 7.1 mmol/L, respectively, decreasing to control during recovery. In arterial and venous plasma, [K+] increased from 4.3 +/- 0.1 to 6.1 +/- 0.2 (p < 0.01) and from 4.5 +/- 0.2 to 5.3 +/- 0.2 mmol/L (p < 0.01), respectively, decreasing to control during recovery. The efflux of Lac- out of erythrocytes against an electrochemical concentration gradient suggests the presence of an active transport system. Efflux of K+ from erythrocytes as blood passes across inactive muscle affords an important adaptation to the K+ release from muscle activated in heavy exercise.


Effects of exercise on maternal glycogen storage patterns and fetal outcome in mature rats. The purpose of the present study was to examine the effects of exercise on maternal glycogen storage patterns and fetal outcome in mature (approximately 12 months of age) Sprague-Dawley rats. The exercise consisted of treadmill running at 30 m.min-1, on a 10 degree incline, for 60 min, 5 days per week, for 4 weeks prior to pregnancy, which continued until day 19 of gestation. In mature animals, chronic exercise increased (p < 0.05) liver glycogen concentration in both pregnant and nonpregnant rats. In pregnant exercised animals, the glycogen concentration of the maternal liver increased almost twofold (p < 0.05) compared with the sedentary pregnant group. There was no difference in the amount of glycogen stored in the gastrocnemius or soleus muscles in response to training, pregnancy, or chronic maternal exercise in the mature rat. In the pregnant groups, there were fewer (p < 0.05) viable fetuses and more (p < 0.05) resorption sites than in young rats. In addition, exercise during pregnancy in the mature animal decreased (p < 0.05) fetal body weight. These results demonstrate that a conflict may exist between maternal exercise and fetal demands for energy in the mature rat. This conflict seems to favour the maternal system, as evidenced by the enhanced maternal liver glycogen storage and the negative effect on fetal growth.


Echocardiographic findings and the increased risk of stroke in nonvalvular atrial fibrillation. We studied whether cardiac abnormalities contribute to the increased risk of stroke in patients with nonvalvular atrial fibrillation (NVAF). M-mode and 2D echocardiography were performed in four age- and gender-matched groups: 20 stroke patients with NVAF, 20 patients with NVAF who had not suffered a previous stroke, 20 stroke patients with sinus rhythm, and 40 healthy controls. Their mean age was 77 years. The two groups with atrial fibrillation differed from healthy controls in that they had more 2D-echocardiographic findings of severe left-ventricular-wall-motion abnormalities (p < 0.05) and tended more often to have enlarged left ventricles, and hypertrophic and congestive cardiomyopathy. Left atrial diameter was 47 mm compared to 41 and 39 mm in the two groups with sinus rhythm (p < 0.001). Intracardiac thrombi were only found in the two atrial-fibrillation groups (with stroke: 15% without stroke: 5%). Aortic sclerosis was common in all groups (30-60%), as was mitral annulus calcification (10-20%). The only significant difference between the two atrial-fibrillation groups was a higher frequency of earlier ischemic heart disease in the stroke group. Both atrial-fibrillation groups had cardiac abnormalities predisposing for embolic as well as thrombotic stroke.


Left ventricular filling dynamics by Doppler echocardiography in dilated cardiomyopathy: one-year follow-up in patients treated with captopril compared to placebo. The role of impaired diastolic function in determining the pathophysiology of congestive cardiomyopathy was only recently appreciated. In the present study, echocardiography and Doppler cardiography were used to determine changes in cardiac size and transmitral filling dynamics over a 1-year period in patients with congestive cardiomyopathy and determine the effect of captopril on these changes. The study population consisted of 27 patients with congestive heart failure in spite of therapy with digitalis and diuretics (NYHA class 3.2). Fifteen patients were started on placebo and 12 on captopril. Noninvasive evaluation was performed at 6-month intervals. Left ventricular size and left ventricular ejection fraction did not change significantly in either group. Forward stroke volume improved significantly only in patients on captopril compared to placebo (p < 0.05). No significant changes in transmitral flow dynamics were observed in the placebo group whereas the captopril-treated group showed a decrease in the peak velocity, flow velocity integral and rate of rapid filling wave (E) and an increase in the peak, integral and rate of filling during atrial contraction (A). The E/A ratio did not change significantly over time in the placebo group, whereas a reduction in the ratio was noted in the captopril-treated patients. These changes are sustained over 1 year with concomitant improvement in stroke volume, exercise duration and functional class.


Fasting insulin and left ventricular mass in hypertensives and normotensive controls. The mechanism by which increased left ventricular (LV) mass leads to increased coronary heart disease morbidity and mortality is unknown. We evaluated the relation between fasting insulin and echocardiographic LV mass in hypertensives off medication and normotensive controls, controlling the analyses for blood pressure (BP) and body mass index (BMI). Fasting insulin (p = 0.0217) was the most significant predictor of LV mass in hypertensives, while BMI (p = 0.0265) and diastolic BP (p = 0.0159) were the only significant predictors of LV mass in controls. The relation between fasting insulin and LV mass was not confounded by obesity in hypertensives, but obesity and fasting insulin may interact to predict LV mass.


Mechanisms involved in cardiac enlargement and congestive heart failure development after acute myocardial infarction. For 3 months, we followed up 40 patients with acute myocardial infarction, 20 were randomly assigned to treatment with captopril and 20 to placebo, to elucidate mechanisms inducing left ventricular volume enlargement and development of congestive heart failure. Echocardiographic follow-up could be obtained in 28 patients, 11 of whom showed more than a 10% increase in left ventricular systolic and/or diastolic volumes (captopril n = 3/15, placebo n = 8/13, p = 0.05). Volume increase was significantly associated with an impairment in exercise capacity (VO2 max in patients with vs. without volume enlargement 24.7 +/- 1.7 vs. 29.5 +/- 1.9 ml O2/kg/min; p < 0.05). Plasma renin activity, angiotensin II and catecholamines were normal in the acute and chronic postinfarction phase in patients on placebo as well as in patients 12-24 h after captopril intake. Plasma atrial natriuretic peptide concentration (ANP) was increased immediately after myocardial infarction, but ANP levels almost normalized in patients with captopril treatment, while they continued to be elevated in patients on placebo. The only technical parameter able to predict left ventricular volume increases was the sphericity index (28.7 vs. 35.7; p = 0.07). We concluded that morphologic deformation and filling pressures as estimated from elevated ANP levels are major factors promoting remodelling following myocardial infarction. ACE inhibitors might exert their favorable effect predominantly by reducing filling pressure.


Biphasic changes (initial increase and late decrease) in coronary sinus venous oxygen saturation during anginal attacks induced by intracoronary acetylcholine in patients with variant angina. In order to evaluate the effects of intracoronary acetylcholine on coronary resistance vessels, oxygen saturation in coronary sinus blood was continuously measured to compare its dynamic changes during intracoronary injection of acetylcholine in both patients with variant angina and control subjects. Group 1 consisted of 6 patients without coronary artery disease. Group 2 consisted of 10 patients with variant angina and spasm in the left anterior descending coronary artery. A fiberoptic reflection oximetry system was used for the continuous measurement of coronary sinus venous oxygen saturation. Acetylcholine (20 micrograms) was injected directly into the left coronary artery over 30 s. In the group 1 patients, coronary sinus venous oxygen saturation was increased from 39 +/- 2% (mean +/- SEM) to 54 +/- 3% at 30 s, continuously climbed to 70 +/- 3% at 60 s and then gradually decreased to 53 +/- 5% at 120 s after the initiation of intracoronary injection of acetylcholine. In contrast, in the group 2 patients, coronary sinus venous oxygen saturation was transiently increased from 39 +/- 2% to 56 +/- 4% at 30 s, reversed, decreased to 52 +/- 4% at 60 s and then rapidly decreased to 36 +/- 3% at 120 s with the onset of chest pain associated with electrocardiographic ischemic changes. Coronary arteriography during attacks demonstrated a total or subtotal occlusion of the left anterior descending coronary artery due to severe spasm in all of the 10 patients. The extent of increases in coronary sinus venous oxygen saturation at 30 s after acetylcholine injection was not significantly different between the two groups (group 1: 15 +/- 4%, group 2: 17 +/- 3%). Heart rate, blood pressure and rate-pressure product were essentially unchanged at 30 s after intracoronary injection of acetylcholine in both groups. These data suggest that in control adult humans, coronary blood flow was increased through dilatation of resistance vessels by acetylcholine, while in patients with variant angina, coronary blood flow was transiently increased by dilatation of resistance vessels, after which it was suddenly decreased by spasm of an epicardial artery induced by this agent. Relaxant responses to acetylcholine of coronary resistance vessels appear to be preserved well in patients with variant angina.


Cardiovascular effects of cigarette smoking. The risk of cardiovascular morbidity and mortality is greatly affected by cigarette smoking. In order to study the pressor response to smoking, 10 normotensive and 10 mild or moderate essential-hypertensive smokers (> 20 cigarettes daily) were compared with 2 comparable groups of non-smokers. All subjects were asked to smoke 4 cigarettes during 1 h; blood pressure (BP) and heart rate (HR) were monitored beat-to-beat by a non-invasive device (Finapres Ohmeda) during the smoking period and during the immediately preceding non-smoking hour. Furthermore, all subjects underwent 24-hour ambulatory BP monitoring. In all groups, each cigarette induced a similar and statistically significant increase from baseline for both BP and HR. The recovery from the marked rise in BP and HR was very slow so that in the smoking hours BP and HR were persistently higher than in non-smoking hours; there were no statistically significant differences between the four groups. During 24-hour ambulatory monitoring both normo- and hypertensive smokers showed higher BP values and higher BP variability in comparison with the respective non-smokers' group. In conclusion, smoking habits were associated with a persistent increase in BP in each group we studied, possibly contributing to a smoking-related cardiovascular risk.


Reproducibility of measurements of coronary narrowings by videodensitometry and by digital calipers. Computer-assisted videodensitometry has been shown to be a reliable and reproducible method of measuring absolute and relative coronary narrowings. Using a commercially available analyzer (Vanguard XR70) we confirmed intra- and interobserver reproducibilities in 34 narrowings in 9 patients. Analyses were performed on normal area and diameter, stenotic area and diameter, percent area stenosis and percent diameter stenosis. For all 6 analyses, excellent intra- and interobserver correlations were found (r = 0.93-0.98), with slopes close to 1 and intercepts close to zero. Caliper measurements (Mitutoyo Digimatic) of the same lesions by the same observers showed good inter- and intraobserver reproducibility for percent diameter stenosis (r = 0.90 and 0.86), with mean interobserver difference of 1.67 +/- (SD) 6.4% and intraobserver difference of 2.97 +/- (SD) 7.9%. However, less good correlations were found between caliper and videodensitometric measurements of percent diameter stenosis; r = 0.61 and 0.76 for the two observers. These data suggest that videodensitometry is a highly reproducible quantitative angiographic method, suitable for documenting changes in the severity of coronary artery lesions, both spontaneous or related to interventions. Caliper measurements do not provide the same degree of accuracy, but they have acceptable reproducibility in measuring diameter stenosis. As such, they are also suitable for assessing changes in severity of coronary artery lesions in individual patients.


Percutaneous transluminal coronary angioplasty in unstable and stable angina pectoris: a comparison of immediate success and complications. To determine the success rate and the safety of percutaneous transluminal coronary angioplasty in patients with unstable angina pectoris (group 1) versus stable angina (group 2), we studied 299 consecutive patients who underwent coronary angioplasty of 373 consecutive lesions. Of these patients, 149 had unstable angina pectoris and dilation of 188 arteries. The success rate was high and similar in both groups (95 and 93%, respectively). The groups did not differ in regard to the lesion characteristics, vessels and number of sites dilated except for an increase in the presence of thrombus in the unstable angina group (p < 0.03). Although there was a higher incidence of coronary thrombus and more acute myocardial infarction in group 1, the major complication rate did not differ from that of group 2 and was low in both of them (3 and 2%, respectively). No deaths occurred. Six patients (3 in each group) needed urgent coronary artery bypass grafting while 3 additional patients developed acute Q-wave myocardial infarction (all of them in group 1). Thus, percutaneous transluminal coronary angioplasty is a safe and successful procedure in patients with unstable angina as well as in patients with stable angina pectoris.


Color Doppler mapping of aortic regurgitation in aortic stenosis: comparison with angiography. Color flow Doppler mapping has become the principal noninvasive method used for the qualitative grading of aortic regurgitation (AR). However, the performance of the color Doppler method in patients with AR accompanying aortic stenosis (AS) has not been studied. We therefore compared results of color Doppler and semiquantitative angiographic grading of AR in 32 patients with AS (mean valve area = 0.7 cm2) undergoing supravalvular aortography in the course of cardiac catheterization. Color Doppler demonstrated AR in all 27 patients who had AR by aortography. As expected, neither the maximal jet area nor the jet length discriminated patients by angiographic grade. The best correlation between color Doppler and aortography occurred when the ratio of maximal jet height (JH) to left ventricular outflow tract (LVOT) height was used to grade AR on a scale of 0-4. Four of 5 patients without AR by aortography had either absent or grade 1 AR by color Doppler. Although there was considerable overlap of color Doppler grades in patients with 1+ AR by aortography, grade 3 or 4 AR by color Doppler was always associated with III+ or IV+ AR by aortography. Thus, color Doppler sensitively depicts AR in patients with AS, and the ratio of JH to LVOT height by color Doppler correctly identifies patients with III+ or IV+ AR by aortography. Methods for distinguishing among milder grades require further evaluation.


Single coronary artery: a report of 2 cases. An isolated single coronary artery is a rare congenital anomaly. We report 2 patients each of whom had a single coronary artery with an obstructive atherosclerotic lesion in one of its branches. In the first patient angioplasty was successfully performed using a perfusion catheter whilst in the second, the procedure was considered inappropriate as the patient had chronic total occlusion.


Regulatory mechanisms of myocardial hypertrophy and fibrosis: results of in vivo studies. Left ventricular hypertrophy is a major risk factor associated with the appearance of adverse cardiovascular events. A distortion in myocardial structure, mediated by an abnormal accumulation of fibrillar collagen within the adventitia of intramyocardial coronary arteries and neighbouring interstitial spaces, alters the electrical and mechanical behaviour of the myocardium. The mechanisms responsible for the regulation of cardiac myocyte growth and collagen accumulation are therefore of considerable interest. Herein we review results of in vivo studies conducted in the authors' laboratory that addressed these issues in various experimental models. The findings indicate that in arterial hypertension myocardial hypertrophy is related to ventricular systolic pressure work. Myocardial fibrosis, on the other hand, is not related to haemodynamic workload, but rather the presence of mineralocorticoid excess relative to sodium intake and excretion. Accordingly, fibrosis can appear in both the hypertensive left and non-hypertensive right ventricles. Pharmacological probes, administered in variable doses, were used to further test and support this hypothesis. In both primary and secondary hyperaldosteronism, it was possible to prevent the pathological structural remodelling of the myocardium with an aldosterone receptor antagonist, while in unilateral renal ischaemia ACE inhibition was similarly cardioprotective. Other studies demonstrated that it was feasible to regress the fibrous tissue response and normalise diastolic stiffness. This concept of cardioreparation suggests that heart failure due to this type of structural remodelling may be reversible.


Left ventricular hypertrophy, myocardial blood flow and coronary flow reserve. In this review, the coronary haemodynamics of hypertrophic heart disease are discussed with reference to data published over the last 15 years. Coronary reserve is reduced in the presence of concentric cardiac hypertrophy, but is similar to normal in hypertrophic obstructive cardiomyopathy and aortic stenosis, despite marked left ventricular hypertrophy. A moderate decrease in coronary reserve is found in aortic incompetence and in dilated essential hypertension. In hypertensive heart disease, improvement in coronary reserve can be achieved by long-term vasodilator therapy.


Clinical importance of coronary perfusion pressure in the hypertensive patient with left ventricular hypertrophy. In patients with severe left ventricular hypertrophy (LVH), but no significant coronary artery disease (CAD), acute lowering of diastolic blood pressure (DBP) to less than 85 mm Hg is reported to result in a 26% fall in coronary blood flow and an increase in myocardial oxygen demand; S-T segment and T-wave changes in the ECG are observed when DBP is acutely lowered to the 70s in these patients. In the presence of good resting left ventricular function, acute lowering of DBP to the 60s in well-controlled hypertensives on a beta-blocker, with either CAD or LVH, results in a mean increase of about 20% in ventricular ejection fraction. By contrast, patients with a combination of CAD and LVH experience a mean 6% fall in ejection fraction implying poor left ventricular functional reserve. In low risk populations, which exclude patients with severe ischaemia, diabetics and smokers, the lower the DBP the fewer the number of myocardial infarctions. However, in heterogeneous hypertensive populations which include high risk patients, such as ischaemics and diabetics (e.g. the MRFIT population), there is a strong U- or J-curve relationship between DBP and CAD deaths. Meta-analysis of high quality studies involving heterogeneous populations has shown that the U- or J-point is at 84 mm Hg and probably relates to high risk patients with ischaemia and/or LVH. Recent data from the Framingham group indicate that the patients most at risk are those with a combination of CAD and LVH: these patients showed a marked U-shaped curve with the U- or J-point at about 85-89 mm Hg DBP.(ABSTRACT TRUNCATED AT 250 WORDS)


Left ventricular hypertrophy and mortality--results from the Framingham Study. Data on the prognostic implications of left ventricular hypertrophy (LVH) in the Framingham Study based on routine ECG, echocardiogram (ECHO) and X-ray determination with 36 years of follow-up indicate that LVH has emerged as a powerful indicator of rapidly evolving lethal atherosclerotic disease, whether determined by ECG, ECHO or X-ray. Cardiovascular morbidity and mortality increase progressively with left ventricular muscle mass from lowest to highest values. The ECG and X-ray versions of LVH each independently contribute to the risk of cardiovascular events; each adds to the risk associated with the other, and those with both are at greater risk than those with either alone. Risk ratios associated with ECG-LVH are substantial and are greatest for cardiac failure and stroke, but coronary disease is the commonest and most lethal sequela. LVH is reversible, the anatomical variety more so than ECG-LVH, and reversal of this toward normal appears to confer greater benefit for the anatomical rather than the ECG manifestation of LVH. The risk of cardiovascular disease associated with LVH is not uniform, varying widely depending not only on whether there is concomitant ECG and anatomical evidence of hypertrophy but also on the associated hypertension, glucose intolerance, lipid profile and cigarette smoking habit. This suggests that there is much to be gained in correcting those associated risk factors which also promote the development of LVH.


Impact of the daily blood pressure load on the development of hypertensive heart disease. Blood pressure (BP) load is a method of data analysis for 24-hour BP recordings that calculates the percentage of elevated pressures above a defined threshold value. This paper reviews the relevance of BP load to indexes of hypertensive target organ disease and the usefulness of the load in assessing antihypertensive therapy. Studies that have assessed the range of BP load and the associations between the load and indexes of hypertensive target organ disease in untreated subjects were included in this review. Additional data from a therapeutic trial have been newly evaluated to assess the effects of lisinopril monotherapy on systolic and diastolic BP load in 30 mild-to-moderately hypertensive patients. BP load, whether taken as a percentage of elevated pressures over the day and night, or as integrated areas under the BP curve, predicts pathological indexes of hypertensive heart disease. In the therapeutic evaluation of BP load, lisinopril reduced systolic BP load from 75 to 44% (p < 0.001) and diastolic BP load from 56 to 29% (p < 0.001). The data have shown a close relationship between BP load and indexes of hypertensive disease. This finding and the ease of use in clinical therapeutic trials suggest that BP load reduction is a worthwhile parameter to follow in studies of antihypertensive drugs.


Selection of antihypertensive therapy: cardiac and extracardiac considerations. There are four possible pathophysiological mechanisms which may relate left ventricular hypertrophy (LVH) with cardiovascular morbidity and mortality: LVH diminishes left ventricular filling; LVH decreases coronary reserve and hampers myocardial oxygenation; LVH is commonly associated with ventricular arrhythmias, and with long-standing LVH, left ventricular contractility decreases. LVH can be reduced by a range of antihypertensive drugs, although not all drugs are equipotent in this regard. Two recent meta-analyses have indicated that ACE inhibitors are among the most powerful monotherapeutic modalities to reduce LVH. Calcium channel blockers are almost as effective, whereas beta-blockers and diuretics seem to have a lesser effect, despite equipotent antihypertensive properties. Reducing LVH with ACE inhibitors and calcium channel blockers has been shown to improve contractility and left ventricular filling, and diminish ventricular ectopy. A preliminary study also indicates that coronary reserve increases after reduction in LVH. Despite these promising pathophysiological signs, it remains unknown whether or not a reduction in LVH will reduce morbidity and mortality over and above the reduction achieved by a reduction in arterial pressure alone.


[A population-based study on incidence of idiopathic cardiomyopathy in Nanjing, 1985-1989]. The epidemiology of idiopathic cardiomyopathy (ICM) is largely unknown among Chinese population. The purpose of this study was to document the incidence of ICM in the entire residents aged less than 60 years in Nanjing city during the five year period from 1985 to 1989. Using the case registered method it was identified that 275 new cases of ICM collecting from all of the clinically diagnosed outpatients and inpatients in the 14 related hospitals within the city among 2,098,175 residents for years 1985-1989. Over all incidence rate was 2.6 per 100,000 person-years, the age-and sex-adjusted average annual rate being 2.1 per 100,000 directly according to the standardized population of China in 1964 (95% confidence interval 1.9-2.2). This incidence rate was increased from 1.7 per 100,000 in 1985 to 3.3 per 100,000 in 1989 and progressively increasing with aging especially in the groups over 20 years old. Among these 275 patients with ICM, 134 were classified to idiopathic dilated cardiomyopathy (IDCM) and 132 to idiopathic hypertrophic cardiomyopathy (IHCM). Both the average annual incidence rates of IDCM and IHCM were 1.3 per 100,000 and the age-and sex-adjusted rates were 1.1 per 100,000 (95% CI 0.9-1.2) in IDCN and 0.9 per 100,000 (95% CI 0.8-1.0) in IHCM, respectively. The incidence rate of ICM in male was 3.0 significantly higher than 2.2 per 100,000 in female especially in IHCM. The result of this survey is first provided with incidence data of ICM on a broad general population-based study in our country and may be of value in further studying its epidemiology and etiology.


[Selection of DSP points in second stage and their presentation]. The principal of selecting DSP points is discussed. Because social and economic development is not balance, developing level of health business and health situation of population are obvious varies in different areas of China. In order to ensure that health information from surveillance population can be used to infer health situation of national population, the feature of geographic, administrative areas and various health situation in different areas are considered. The principals of selecting DSP are: 1. To assure well-balance of geographic distribution of DSP. 2. To assure well-balance of distribution of DSP in different kind of areas, according to above 9 index, GNP, illiterate rate, birth rate, infant death rate, rough death rate, ratio of 0-14 years people to total people, ratio of about 65 years people to total people, ratio of labor in industry to total people, and ratio of labor in agriculture to total people. The way of select DSP is: Multistage stratified random sampling (PPS). Meanwhile in order to avoid systematic error, about 15% points which are no qualified were changed. Therefore whether data from DSP can be represented health level of population of whole nation has been tested. The conclusion is that the data from DSP can indeed do so.


[Study on epidemic factors of the decline of cervical cancer mortality in Shandong province]. It is well known that the decline in the incidence or mortality rates of cervical cancer was very significant in the eighties as compared with in the seventies in China. In Shandong province the mortality of cervical cancer was reduced by 76.3 percent during from 1974 year to 1989 year. According to the survival time of patients with cervical cancer in Cangshan county showed that the decline in the mortalities was due to cut down the incidences of it. A birth cohorts study of mortality of the disease was made in the period time of from 1970 to 1989 in Qixia county. The results of which indicated that the cohorts of women who reached puberty after 1949 have much lower rates of cervical cancer than the cohorts of women who reached sexual maturity before that time. The correlation analysis showed the main reason for the decline was related to the elimination of the venereal diseases by the end of 1964 year. The birth control programme having been carried out since the beginning in the sixties also found in relation to the decline of cervical cancer in the eighties.


[Seroepidemiological study of hepatitis B virus x antigen (HBxAg) and anti-HBx antibodies in patients with hepatitis B]. A total of 437 patients with hepatitis B were tested for serum HBxAg and anti-HBx in a seroepidemiological study. It was shown that the HBxAg positivity rate was 3.66% (16/437), the anti-HBx positivity rate was 2.97% (13/437). HBxAg was most frequently present in HBsAg, HBeAg, and anti-HBc positive, but anti-HBe negative sera. Anti-HBx was most frequently present in HBeAg and anti-HBc positive, but HBsAg and anti-HBe negative sera. Both the presence of HBxAg and anti-HBx antibodies showed no significant relationship with the presence of serum anti-HBs antibodies. These results indicated that serum HBxAg/anti-HBx system was related to the replications of HBV in the HBV infected human body, and anti-HBx were not protective antibody.


[Epidemiological survey of hypertension in the remarried families]. In order to inquire into the relative importance of the genetic and the environmental factors in the hypertension, we made generally survey of 484 remarried families in Tangshan. We made comparison for the prevalence rate of hypertension of the familial members whose blood relationship is not the same. The results of research suggest that the effect of genetic factors is relatively more important than the environmental factors in the familial aggregation of blood pressure.


[Report on first finding an epidemic of Scrub typhus in north rural areas]. In the autumn of 1989 and 1990, an epidemic of Scrub typhus occurred in north rural areas in Tianjin. The authors investigated the epidemic on clinical, epidemiological, serological and etiological features, 44 patients were diagnosed serologically or clinically as Scrub typhus and 42 of them (95.5%) were diagnosed serologically by IFA method. 10 sera specimens collected from the patients were determined distinctively by CF method, 8 of them were > or = 1:20 titre to Gilliam type antigen of tsutsugamushi. The try for isolating pathogens failed of success. The epidemic areas is situated in 39.45'-40.05' north latitudes and showed it was the new epidemic area in the north of China.


[Study on the infections of U. urealyticum, M. hominis, and C. trachomatis in patients with venereal diseases and healthy controls in three areas of China]. Two hundred and thiry-nine patients with venereal diseases and 264 healthy controls, from Yichang, Liuzhou, and Beijing, were detected for the antibodies to Ureaplasma urealyticum (Uu). Mycoplasma hominis (Mh), and Chlamydia trachomatis (Ct) by indirect hemagglutination (IHA) in 1990. The results showed that: 1) in patients with venereal diseases, the positive rates was the highest in Ct (27.62%), higher in Uu (17.57%), and lower in Mh (4.18%); 2) the levels of antibody to Ct and Uu were significantly higher in the patients than in the healthy controls; 3) in the patients, the positive rate of antibody to Ct was the highest in Beijing (55.88%), whereas, the lowest in Yichang (15.28%); the prevalence rate of antibody to Uu was the highest in Liuzhou (26.23%), whereas, the lowest in Beijing (5.88%); the level of antibody to Mh was not significantly different in the areas mentioned; and 4) the patients with venereal diseases were commonly complicated with infections caused by Ct, Uu, and Mh, there was a new problem to control and treat venereal diseases.


[Prospective epidemiological study on the efficacy and safety of female tubal sterilization by chemical instillation]. This is a prospective study on clinical efficacy and safety of female sterilization by chemical agents. A total number of 1705 subjects were randomly divided into two groups. Phenol mucilage (PM) was used in group 1 (834 cases) and phenol-atabrine paste (PAP) was used in group 2 (871 cases). All the characteristics of the subjects were proportionate and comparable to two groups. The follow-up rate was 98.5% at the end of 2 years. Using life table analysis, the results show that the cumulative success rate per 100 women of two groups using PAP and PM was 97.4% and 91.1% respectively. There was significant difference between the two groups. The efficacy of the methods was related with the developed length of roentgenographic shadow after instillation. Multiple discriminatory analysis showed the same results as above. There was no severe complication in all cases. The post-instillation fever rate was 8% in group PAP and 4.4% in group PM, respectively. Our results indicate that female sterilization with the use of chemical agents mentioned is a simple, safe and reliable method in preventing pregnancy.


[Investigation of rodents and Ixodes for Lyme disease and four strains of Borrelia burgdorferi first isolated from Ixodes granulatus Supino, Rattus confucianus and R. norvegicus in Fujian province]. With BSK II medium, 4 strains of Borrelia burgdorferi was isolated from Ixodes granulatus Supino, Rattus confucianus and R, novregicus, which Ixodes and Ruttus all captured from forest areas in northern of Fujian province where have found Lyme cases. These isolated strains were identified by Institute of Epidemiology and Microbiology, Chinese Academy of Preventive Medicine.


Left or right, up or down: a case for positioning of unconscious head-injured patients. Nursing care activities have been proved to cause increases in intracranial pressure (ICP) which could be detrimental to the patient's health. Because positioning is one of the activities that causes the greatest pressure changes it was evaluated in this study. Cumulative increases also occur when nursing care activities are carried out in quick succession. The analysis of the data and literature suggest that the backrest position with the head of the bed elevated 30 to 45 degrees is the best position for a patient with increased ICP. If further research should prove that this position has a negative influence on the cerebral perfusion pressure, these recommendations will have to be revised.


Contemplating a challenging future: a public management approach to health services. A varying proportion of health services in all societies is delivered by public sector institutions. Managing these public sector service institutions for performance represents a major management challenge. This management challenge is amplified for South Africa as a country which is contemplating major changes while being simultaneously confronted with having to cope with problematic results of the past and the challenges of development. In this article a public management model is used to analyse relevant health trends and provisional management strategies are provided to assist health managers to cope with these challenges. Finally a checklist for personal survival is presented for personal evaluation and future planning.


[Psychosocial, economic, sexual and religious related needs and problems of women with carcinoma of the breast]. The psychosocial, economic, sexual and religious related needs and problems of women with carcinoma of the breast are explored. White women with carcinoma of the breast experience particular needs and problems related to psychosocial, economic, sexual and religious matters. These needs and problems are also influenced by a number of aetiological factors. Apart from the tension caused by a diagnosis of carcinoma, and particularly one of carcinoma of the breast, the treatment which these women receive contributes to their needs and problems. The research clearly showed that the majority of women did not experience serious problems in coping with their illness--there was a universally low average intensity of needs and problems. They did, however, require help and support in coping with and accepting the consequences of the carcinoma and the attendant treatment.


An investigation into the knowledge mothers have about children's growth charts. 218 Mothers who attended the Well Baby Clinic were interviewed to assess their understanding and interpretation of the growth chart. Results were disappointing and recommendations are made.


[The status of clinical evaluation at South African universities]. The fact that clinical evaluation is a difficult and complex task of nursing education has been emphasized in the nursing literature since the early seventies. It is, nevertheless, a most important component of the teaching-learning process of nursing students and it has definite advantages. It: contributes to the improvement of the standard of nursing care; helps to identify problem areas for research; and contributes to high level professional preparation. In the light of these factors the aims of the study were to: determine and describe the position of clinical evaluation as a component of the teaching of undergraduate students in departments of nursing at universities in Southern Africa; draw up a proto-theoretical model for clinical evaluation. The second aim will be fully discussed in a follow-up article. The empirical data showed that nursing educationists in Southern Africa are not entirely up to standard regarding the skills required for clinical evaluation.


Disease-related needs of black patients with cervical cancer. The high incidence of cervical cancer amongst South African black women is complicated by late presentation for treatment as well as by misconceptions and ignorance which adversely affect the quality of their lives. The aim of the research was to determine the disease-related needs of patients suffering from cervical cancer which would serve as a basis for planning on providing for these needs. Needs for the following were identified: Education on early detection in the community. Education on nutrition and hygiene. Information on and assistance in obtaining financial relief by means of subsidized transport and disability pensions.


An exploratory study of the ways in which mothers keep their infants occupied. The mother child relationship can help or hinder the social, emotional and intellectual development of the infant. Research has shown that the interaction between mother and child can affect the child's cognitive development. Research has shown that mothers from the lower socio-economic groups do not stimulate their babies optimally and that this may affect the children negatively. In this study 86 underprivileged mothers from two different cultural backgrounds were asked to describe the ways in which they kept their infants occupied during the first year of their infants' lives. The differences between the two groups are discussed and recommendations are made.


[The contribution of unit managers in the education of student nurses]. The contribution of a group of unit managers towards student education, as well as the problems related thereto, has been investigated contextually by means of an explorative descriptive study, utilising structured interviews. The results indicate that, although unit managers have a positive attitude towards student education, they lack insight regarding the programme content, as well as their own informal educational function in the clinical situation. Lack of time and inadequate liaison between the college and unit managers seem to aggravate this problem. The recommendations include the design and implementation of inservice programmes for unit managers, improved liaison between educational and unit staff, as well as role clarification concerning their informal education responsibilities.


[Health education in pregnant women].

[Health education in pregnant women]. Health education and information in pregnancy must be a priority, despite the lack of instruments to evaluate the effectiveness of the education and the fact that positive results can not be guaranteed. During research done for a Masters degree on the utilization of antenatal services by high risk primigravidae at the Tygerberg hospital, patients were interviewed on various aspects that are important during pregnancy, like family planning, breastfeeding, smoking and danger signs that may occur during pregnancy. It was found that education on smoking and alcohol had little impact. However, more patients felt positive about breastfeeding and family planning after they received information about it. A disturbing finding was that patients had very little knowledge about the danger signs that may occur during pregnancy. They did not know the reasons for the examinations and tests performed during pregnancy, although it probably had no negative effect on the attendance of the antenatal clinics. Most of the patients preferred a doctor rather than a nurse to give education and information. It is recommended that health education be looked at critically to ensure that it satisfies the needs of the patients and that the patients' pre-existing knowledge and their educational abilities are taken into consideration. Essential knowledge like the danger signs must be repeated at every visit and the patient's comprehension of it, must be evaluated. It is further not only important to extend the knowledge of nurses on health education, but also to evaluate their competence in giving health education.


The science of nursing: current issues and dilemmas. The question regarding the nature and direction of nursing science, how it is derived or why and whether nursing is a science is a much debated one. This article focuses on an examination of the literature with regard to conceptualizations of science in general and nursing in particular with special emphasis on the nature, purpose, methods and domain of science and nursing science. It looks at the various positions taken, examines the consequences of holding any special position and makes suggestions for achieving excellence in Nursing Science.


[A facilitation skills program for nursing instructors]. The aim of this study is to discuss the role of the nursing teacher as facilitator of psychological growth in the student, with reference to personality characteristics and skills. A facilitation skills programme is applied to a group of nursing teachers and evaluated by means of a pre, post and post-post psychometric evaluation on an experimental and a control group. Significant positive behavioural change manifested in flexibility in the application of values, feeling sensitivity, internal locus of control and the interpersonal skills of respect, empathy, realness and concreteness. It is recommended that the facilitating role be extended as communication dimension in practical nursing.


[The teaching function of the registered nurse--I]. A descriptive exploratory survey was undertaken by means of a questionnaire submitted to student nurses and registered nurses of hospitals affiliated with a nursing college in the Transvaal. The aim of the study was to establish whether, and to what extent, the training function of the ward sister is realised in practice. Analysis of the data showed the ward sister to be aware of her training function and her responsibility towards the student nurse as learner. It appears that the ward sister believes herself to be adequately involved with the basic care of patients and making a significant contribution to the training of student nurses. However, the observations and the experience of the student nurse differ from this point of view. She is of the opinion that more can be done in the ward to help her achieve her training needs. The fact that in many cases she is primarily considered as a worker, comes as a great disappointment.


Selection of student nurses at Bafokeng Nursing College. Bafokeng Nursing College is a privately owned institution situated at the Impala Mines in Bophuthatswana. It selects and trains student nurses from all parts of Southern Africa in the comprehensive four-year course who at qualifying are free to work for Genmin or anywhere else in the country. The College is affiliated to Medunsa in offering the four-year comprehensive course. Selection is limited because of limited facilities. The old selection process was evaluated in 1985 and the new selection process started functioning in 1986 when the new course was offered for the first time at the College. With the new selection process, the drop-out rate is very low, the pass rate has improved and the quality of nursing care is improving.


Primary mental health care: indications and obstacles. This paper considers indications and obstacles for the development of primary mental health care practice in both developed and under-developed countries. Both are considered as this represents the South African reality. While a significant body of literature has documented the need for primary mental health care, the obstacles (especially in terms of the co-modification of health) to its fruition are seldom addressed.


[Computer-assisted instruction in nursing]. According to Kotzé (1987:5) the numbers of student nurses showed a constant drop of 10% from 1981 until 1986. It appears that the ratio between the registered nurse and the population will severely worsen. It is therefore necessary that the educational standard of students nurses must be as high as possible to render a comprehensive service to a growing population. Computer-aided instruction can also play a role in the training of student nurses but can also help to keep student nurses as well as registered nurses in touch with the latest developments and introduce them to advanced technology like the computer.