[Mishaps with anti-arrhythmic agents used to reduce mortality after infarction].

The presence of isolated and/or repetitive ventricular arrhythmias following myocardial infarction identifies a group of patients at increased risk of death. The availability of anti-arrhythmic drugs, noticeably drugs with class I activity, efficient at suppressing arrhythmias has led to the hope that their administration could reduce post-myocardial infarction mortality. However, this hypothesis has not been confirmed. The Cardiac Arrhythmia Suppression Trial, which was designed to have the power to test the hypothesis that suppression of ventricular arrhythmias is associated with a decrease in mortality following myocardial infarction, even showed an increase in mortality with two drugs with class I activity. Several meta-analyses have confirmed that administration of class I antiarrhythmic drugs is of no clinical benefit in patients with non sustained ventricular arrhythmias following myocardial infarction. Ongoings studies are testing the hypothesis that such benefit could exist with amiodarone. The clinical benefit of beta-blockers, in terms of reduction of both total and sudden death post-myocardial infarction, has been clearly documented and mandates their administration in this setting. Futures studies of anti-arrhythmic drugs will have to focus on groups of patients at increased risk of arrhythmic death.


[Role of physical effort in the monitoring of coronary disease: under medical treatment, after bypass, after angioplasty].

Exercise tests must be performed only in hospitals and private clinics equipped for intensive care. Electrocardiographs must be fitted with a computer-assisted system for averaging and smoothing. In all but special cases it would be preferable to interrupt or delay the anti-angina treatment, so that the degree of ischaemia can be quantified. In this way, the severity of coronary lesions, the risk of arrhythmia and the prognosis for life can be predicted with good statistical certainty. In addition, the patient's fitness for work can easily be evaluated. As years go by, the ischaemia may be found to have become worse, and it might be decided to revascularize the myocardium in due course. Following revascularisation exercise tests are used to evaluate its benefits and follow their persistence. In addition, exercise tests are a very useful means of adjusting the antianginal treatment. Finally, exercise tests create a special link between patients and their medical team since they participate, both physically and psychologically, in their own diagnosis and evaluation of treatment.


[Exercise echocardiography in coronary disease].

Exercise echocardiography is a new method used in the investigation of coronary disease. It evaluates the repercussions on regional contractile function of the increase in oxygen consumption induced by physical exercise. It makes it possible to analyse in real time not only the amplitude of endocardial displacement, but also that of parietal thickening and thereby seems to be more precise than conventional ergonomic tests in the diagnosis of myocardial ischaemia. Its recent development owes much to the advent of digital technologies which make it easier and more accurate to interpret the changes observed in left ventricular regional kinetics by comparing the data at rest with those recorded at peak physical effort. When associated with an equally non-invasive ergometric test it is well accepted by the patients. Another of its advantages is its moderate cost. Echocardiographists must devote as much time as necessary to training. Training is indispensable to rapidly capture the images, particularly during efforts, and to reliably interpret the variations observed in left ventricular wall contraction. Exercise echocardiography is still under evaluation. Experience is lacking for the cardiologist to choose, only on its results, the most appropriate treatment for each individual patient, but its help will be appreciated in some difficult therapeutic decisions. Behind this phase of training for, and evaluating this technique several of its main clinical indications can already be outlined.(ABSTRACT TRUNCATED AT 250 WORDS)


[Drug-induced nephropathies].

Drug-induced nephropathies are frequent. Glomeruli, tubes, interstitium and arterioles may be altered. In this paper, we have tried to know if clinical, biological or histological signs of drug-induced nephropathies are similar or different from those observed in idiopathic nephropathies. We demonstrate that drug-induced nephropathies do not present any particular clinical or biological signs. We find that minimal changes and membranous glomerulopathies are the main lesions observed. In contrast, glomerular proliferations are very rare. Drug-induced tubulopathies are characterized by tubular necrosis with variable extension. Interstitial lesions are absolutely identical to those observed in immunologically mediated nephropathies. Vascular lesions are very rare. It should be noticed that evolution of drug-induced nephropathies differs completely from idiopathic nephropathies. Indeed, renal lesions are usually regressive when the drug administration is stopped. In conclusion, it appears that drug-induced nephropathies mimic other forms of nephropathies. It is important to know that some drugs are excellent experimental models to reproduce some aspects of human renal pathologies.


Adaptation and renewal of the gastrointestinal surgeon to meet the continuous challenge of modern gastroenterology.

The treatment of gastrointestinal diseases has entered into a period of rapid evolution. Gastroenterology has in the last 50 years evolved into a major specialty, covering not only complex clinical and diagnostic areas, but inclusive of sophisticated investigative work and major therapeutic endoscopic technology. Unfortunately, the evolution of gastrointestinal surgery has lagged behind. The scope of the gastrointestinal surgeon has become more limited, as potent pharmacotherapeutic probes, invasive radiological techniques and diagnostic and therapeutic endoscopic advances have been implemented. The development of minimally invasive surgical techniques has introduced a new era in surgical management. However, the establishment of new training programs and the acquisition of skills requiring the acquisition of costly equipment are major issues which surgical departments need to address. A novel training and programmatic configuration for the group of physicians involved in the management of gastrointestinal disease is required to meet this challenge. In particular, internists and surgeons must focus on the development of cost and time effective strategies for the management of clinical gastrointestinal disease. It seems likely, however, that adequate resources and management of these undertakings will only be forthcoming if corporate establishments, venture capital groups, medical health insurance institutions and national research agencies develop a consortium approach with medical schools to address these issues.


Gastric acid in vertebrates.

Gastric secretion of hydrochloric acid appears to be unique to vertebrates and is almost ubiquitous in all fishes, amphibians, reptiles, birds and mammals. Comparative anatomy and physiology suggest that gastric acid has evolved approximately 350 million years ago. The similarity of the acid-secreting mechanism across all classes of vertebrates implies a major advantage for selection, but the evidence regarding its precise purpose remains inconclusive.


Adaptation and renewal of the endocrine stomach.

At present at least seven different endocrine cell types have been identified in the stomach. According to their relative frequency and secretion products the antral gastrin producing G cell and somatostatin producing D cell and the fundic histamine producing ECL cell are the best characterized cell types. Total endocrine cell mass is controlled by various factors from inside and outside the stomach. Density of antral G and D cells depends on the presence and absence of food, on the antral pH and on additional humoral and/or neural factors. Gastrin and not gastric pH has been identified as the most important factor regulating the density of fundic ECL cells. Adaptation of gastric endocrine cells to gastric pH and to the presence, abundance or absence of humoral and neural regulators are well known phenomena though only partially understood. Antral G cells increase and antral D cells decrease during long-term achlorhydria which as a consequence leads to hypergastrinaemia. Examples are pernicious anaemia in man and drug-induced acid suppression under experimental conditions. Interestingly, achlorhydria-induced G cell hyperplasia never progresses to gastrinomas. Fundic ECL cell density increases markedly in the presence of long-lasting hypergastrinaemia independently of gastric pH. In contrast to G cells ECL cell hyperplasia may progress to rarely occurring ECLomas. However, this depends on additional conditioning factors as the presence of severe atrophic gastritis as in pernicious anaemia or a specific genetic trait present in patients with gastrinomas associated with the MEN I syndrome.


Does the stomach adapt to Helicobacter pylori?

To shed some light on the question of gastric adaptation to Helicobacter pylori infection, an overview is given of the various histopathological and clinical consequences of H. pylori infection in man. H. pylori infection can be considered as a chronic bacterial infection. For many individuals there is a balance between a low degree of infection and a low degree of inflammation. The microbial or host factors in adaptation of this balance are largely unknown. If and how 'downregulation' of the inflammatory/immune response does occur need further study.


Gastric carcinoma: failed adaptation to Helicobacter pylori.

Helicobacter pylori is the major cause of chronic gastritis. Unlike bacterial infections in general, H. pylori acquisition causes a chronic, usually life-long infection. After acquisition, chronic inflammation (gastritis) appears and develops slowly into atrophic gastritis (with intestinal metaplasia) in a proportion of affected subjects. Inflammation and atrophy result from a failure of the immune system to eliminate the H. pylori infection. In infected stomach, several cascades of reactions are triggered which may result in impairments of structure and function of the gastric mucosa, some of which lesions also increase the risk of gastric carcinoma (CGA). A sequence of events from an early H. pylori infection into an atrophic gastritis has risen a theory that the H. pylori acquisition is a key issue in the development of GCA. Several aspects in the epidemiology and pathogenesis of GCA can be understood and explained by this infectious background. The H. pylori gastritis is unexpectedly common in patients with GCA of both intestinal or diffuse type, and the infection and gastritis precede the development of cancer. In Finland, 70-80% of the GCA cases seem to develop in connection with an H. pylori-positive gastritis or atrophy, 10-15% develop in a normal stomach (genetically determined GCA cases?), and 10-15% are associated with an H. pylori-negative corpus-limited (autoimmune) gastritis and atrophy. Case control studies suggest that the presence of H. pylori related inflammation raises the risk of GCA twofold, and the appearance of atrophic gastritis (and intestinal metaplasia) raises further this risk 2-3 times, as compared to the risk of GCA in subjects with a normal stomach.


Adaptation of the gastric mucosa to stress. Role of prostaglandin and epidermal growth factor.

This study was designed to determine whether repeated exposures to stress lead to the adaptation of the gastric mucosa to stress ulcerogenesis. Wistar rats with intact or resected salivary glands were exposed to a standard period (3.5 h) of water-immersion and restraint stress every other day up to 8 days. The significant reduction in the severity of gastric lesions was first noticed after the second exposure to stress and was maximal after 6-day exposures to stress. This tolerance to stress ulcerogenesis disappeared after a 6-day rest during which animals were not exposed to stress. Histologically, the hemorrhages and edema seen after a single stress were less frequent during adaptation; instead the mucosa regenerated in spite of continuation of exposure to stress. During adaptation, the mucosal blood flow (MBF) and mucosal biosynthesis of PG were markedly increased. Administration of indomethacin (5 mg/kg i.p.) completely abolished gastric adaptation to stress and this was accompanied by about 85% reduction in mucosal generation of PG and significant decrease in the MBF. Salivectomy, which significantly reduced the luminal contents of epidermal growth factor (EGF) in the stomach, delayed and reduced the adaptation. We conclude that the stomach has the ability to adapt to repeated exposures to stress and that this adaptation is mediated, at least in part, by endogenous PG and EGF.


Gastric adaptation to nonsteroidal anti-inflammatory drugs in man.

Adaptation describes the phenomenon in which visible gastric mucosal injury lessens or resolves completely despite continued administration of an injurious substance such as aspirin. Adaptation occurs in man although the mechanism remains unclear. Recent evidence suggests increased cell proliferation and correction of nonsteroidal anti-inflammatory drug induced reduction in gastric blood flow as possibly being important. Gastric erosions and ulcers in chronic nonsteroidal anti-inflammatory drug users represent failed adaptation. Gastric erosions and ulcers in chronic nonsteroidal anti-inflammatory drug users represent failed adaptation. The factors responsible for failure of adaptation are unknown but one clue is that there appears to be a dose-response effect relating anti-inflammatory dose and effectiveness of adaptation (i.e., adaptation is delayed, or less effective, when higher anti-inflammatory doses are administered). Gastric adaptation can be enhanced by co-therapy with synthetic prostaglandins but not with sucralfate or H2-receptor antagonists.


Adaptation of gastric mucosa to chronic alcohol administration is associated with increased mucosal expression of growth factors and their receptor.

In our previous study we found that chronic, intragastric administration of ethanol to rats produces adaptation of the gastric mucosa to subsequent challenge with an acute dose of 50% ethanol. The mechanism of this mucosal tolerance remains unexplained. Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) stimulate cells growth and proliferation in the gastric mucosa with noted trophic effect, protect the gastric mucosa against acute injury and accelerate healing of injured mucosa. Many of these effects are exerted through EGF and TGF alpha action on their common receptor (EGFR). The aim of the present study was to determine the effect of chronic alcohol administration on cell proliferation and gastric mucosal expression and distribution of EGF, TGF alpha and EGFR. Chronic administration of ethanol (1 ml, 50% ethanol, twice daily) significantly increased the extent of gastric mucosal mucous and proliferative cell zones, the number of proliferating (DNA synthesizing) cells and mucosal expression of EGF, TGF alpha and EGFR by 13, 6, and 20-fold, respectively. Thus, adaptation of gastric mucosa to chronic alcohol administration is associated with increased cell proliferation and increased expression of mucosal EGF, TGF alpha and EGFR.


Cellular and molecular basis of intestinal and pancreatic adaptation.

This article reviews the structural and functional changes which develop in the intestine and pancreas in response to a variety of stimuli and which characterise adaptive hyper- or hypo-plasia. It then discusses the principal physiological mechanisms controlling this adaptive growth. In the gut, these include luminal nutrition, endocrine, autocrine and paracrine hormonal influences, growth factors, enterotrophic components of pancreatico-biliary secretions, neural factors, changes in blood flow and mesenchyme-epithelial interactions. The cell biology of adaptive growth involves cell membrane receptors (first messengers) and a cascade of intracellular second messengers, the best studied of which is changes in polyamine metabolism and in related enzymes. The effects of ornithine decarboxylase (ODC) blockade with difluoromethyl ornithine (DFMO) and of diamine oxidase (DAO) blockade with aminoguanidine, are described. In general, DFMO inhibits or prevents adaptive hyperplasia while in the small bowel, aminoguanidine treatment induces 'supranormal' adaptation. However, both the gut and the pancreas transport 'exogenous' (ingested in food and circulating in the blood stream) polyamines across their apical and basolateral membranes. The influence of this exogenous polyamine transport on 'endogenous' (enzyme-regulated) intracellular polyamine concentrations, is largely unknown. Finally, the molecular biology of adaptive growth is described briefly--as illustrated by the use of a growth hormone transgenic model in which mice develop marked intestinal mucosal hyperplasia and increases in the relative abundance of insulin-like growth factor-I (IGF-I) mRNA in the intestine.


Adaptive mutagenesis--cause of alimentary cancer?

The tissues of the alimentary tract react to abnormal functional demands or to injury from environmental chemicals by reactions which involve change in morphology, functional characteristics and cellular proliferation. The work hyperplasia, wound repair or response to xenobiotics may become distorted by inherent, or induced, genomic abnormalities of the affected cells. It seems that some of the reactions are 'programmed' or 'planned' and depend on predetermined changes in gene expression. Although the reactions permit survival in the face of environmental hazards, the necessary alterations in gene expression may predispose to malignant change in the affected cells.


Acid secretion, 1932-92: advances, adaptations, and paradoxes.

This paper reviews the evolution of our understanding of various aspects of gastric acid secretion over the past 60 years. Embryologic aspects and neonatal acid secretion are considered, and the relationship between parietal cell mass and acid secretion and the changing concepts of parietal cell activation are discussed. The effect of aging on acid secretion and the relevance of acid secretion in health and disease are reviewed, and current views on adaptation to therapeutic inhibition of acid secretion presented. The aetiologic link between acid secretion and ulcer disease is re-examined, and the role of pepsin, growth factors, and Helicobacter pylori briefly considered.


Trefoil peptide gene expression in gastrointestinal epithelial cells in inflammatory bowel disease.

Trefoil peptides are a growing group of proteins with interesting structural and functional properties. We have defined the pattern of trefoil peptide gene expression in the ulceration-associated cell lineage (UACL) and in the nearby mucosa in Crohn's disease. In the UACL, human spasmolytic polypeptide (hSP) mRNA is expressed in the acinar and proximal duct cells, while pS2 mRNA and peptide are found in the distal duct cells and in the surface cells. In adjacent mucosa, pS2 mRNA and protein are expressed by goblet cells, with the pS2 peptide concentrated in the area of the Golgi and also in the theca. Ultrastructural immunolocalisation showed the pS2 to be co-packaged in the mucous cell granules before being secreted into the intestinal lumen. In addition, pS2 peptide was demonstrated in local neuroendocrine cells and was also co-packaged with the neuroendocrine granules. The crypts associated with the UACL also showed marked neuroendocrine cell hyperplasia. We conclude that pS2 peptide is secreted locally into the viscoelastic coat covering the intestinal mucosa which surrounds Crohn's disease ulcers. In addition, it is clear that intestinal goblet cells, in addition to producing mucins, are a rich source of regulatory peptides. Moreover, pS2 is clearly co-packaged with neurosecretory granules, which are released through basal and lateral membranes so that the contained peptides can act in a paracrine manner. These findings are interpreted in terms of the epidermal growth factor/urogastrone released by the UACL, stimulating pS2 gene expression in surrounding cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Adaptation in the pharmaceutical industry, with particular reference to gastrointestinal drugs and diseases.

In terms of gastrointestinal diseases, the pharmaceutical industry is having to adapt in the face of great success (e.g. anti-ulcer drugs), continued failure (e.g. cancer therapy) and increasing commercial pressures. Whilst success is evident by the presence of four anti-ulcer agents in the top 25 best-selling drugs, the GI tract remains the major site of cancer, a disease where almost no progress in drug treatment has occurred since the discovery of anti-metabolites. In addition to being a major therapeutic target, the GI tract is also the principal route of drug administration with some one hundred billion unit dosages being ingested per year. Not surprisingly, therefore, the gut reigns supreme as a site of minor side-effects. More serious adverse reactions are also common and those associated with anti-proliferative and anti-arthritic drugs can be life-threatening. Thus an agent to combat adverse GI reactions represents a drug development opportunity in itself. In terms of primary diseases of the gut, the pharmaceutical industry is having to adapt to the uncertainties inherent in developing drugs in markets which are poorly defined because of the absence of effective treatments. Foremost amongst these are neoplastic and inflammatory diseases. Although these represent formidable targets, clinical needs and consequently commercial success would far outweight any gains from developing another generation of anti-ulcer drugs to compete with existing anti-secretory agents.


Adaptation of mitochondrial metabolism in liver cirrhosis. Different strategies to maintain a vital function.

Mitochondrial function and structure in cirrhotic livers from humans or rats show a variety of changes as compared to control livers. Mitochondrial ATP production is reduced in rats with CCl4- or thioacetamide-induced liver cirrhosis and in rats with secondary biliary cirrhosis. Activity of the electron transport chain is decreased in rats with secondary biliary cirrhosis. In rats with CCl4-induced cirrhosis, the mitochondrial content of certain constituents of the respiratory chain (cytochrome a + a3, cytochrome b and ubiquinone) is increased and activities of cytochrome c oxidase and ATPase are elevated. Similarly, in humans with liver cirrhosis, mitochondrial cytochrome a + a3 content is elevated and has been used to assess the risk for hepatectomy. In rats with secondary biliary cirrhosis, compensatory strategies include increased mitochondrial volume per hepatocyte and possibly increased extramitochondrial ATP production (increased glycolysis). Thus, a variety of adaptive mechanisms are used to maintain mitochondrial function in cirrhotic livers.


Adaptation and change in gastroenterology.

Predicting the future is a chancy business. In line with other medical specialties, gastroenterology will be subject to rapid and profound changes in the coming decades and will have to adapt and renew its approach to the way medicine will be practised. The pressures to change will be in several areas. Global demographic, political and economic factors will become more intrusive and rapid communication will end isolationism. Developing EC structures and regulations are likely to increase mobility of medical staff and uniformity in the standards of training and practice. Rapid technological advances will have to be reconciled with finite resources and the ever increasing expectations of our aging population.


Congenital toxoplasmosis: is screening desirable?

Toxoplasmosis, a disease caused by the parasite Toxoplasma gondii, is a worldwide health problem. Infection of a pregnant woman can result in severe fetal morbidity and even death. Moreover, there is increasing awareness that congenital toxoplasmosis can cause blindness, epilepsy and other abnormalities in children and adults. Congenital toxoplasmosis can only be prevented by giving information on how to avoid the infection during pregnancy or by routine serologic screening of pregnant women to identify a recent toxoplasma infection that would allow a timely decision for antibiotic treatment and prenatal diagnosis. Advice to pregnant women to apply hygienic measures during pregnancy can reduce with 63% the toxoplasma infection rate during pregnancy and should therefore become standard obstetrical care. Adequate serological screening for toxoplasmosis is possible and allows selection of patients at high risk for delivering a congenitally infected child. Prenatal diagnosis is accurate in diagnosing correctly infected fetuses around the 20th week of gestation. Whether or not serologic screening for toxoplasmosis should be combined with primary prevention will depend on the incidence of congenital toxoplasmosis in a given geographic area.


Diagnosis of Toxoplasma infection in the pregnant woman and the unborn child: current problems.

Prevention of congenital toxoplasmosis requires identification of non immune women at the beginning of pregnancy, instruction on how to avoid contamination and a serological follow-up of the women until the delivery. The latter is easily achieved by a repeated testing for specific IgG and IgM. Most of the interpretation difficulties arise from results suggestive of recent infection obtained on a first specimen. If no rise in IgG titer is demonstrated on a second serum sample, the use of additional tests studying other Ig-isotypes or acute-phase IgG antibodies can be helpful, mainly as a way to exclude the possibility of infection acquired during pregnancy. Congenital infection can be investigated by biological measurements on fetal blood and by ultrasound examination. Detection of specific IgM and IgA in fetal serum must be interpreted with care because of the existing risk of contamination with maternal blood. Demonstration of Toxoplasma gondii in fetal blood or amniotic fluid by mouse inoculation definitely proves the diagnosis; though less sensitive, tissue culture offers the advantage of a more rapid result. The very promising results obtained by the PCR-method applied to amniotic fluid samples give the hope that it can replace som of the existing confirmatory methods.


Treatment of toxoplasmosis in the pregnant mother and newborn child.

The paper presents a review of different treatment regimens employed for 25 years to prevent and treat congenital toxoplasmosis. Unfortunately, no well-controlled, randomized trials have been performed to evaluate the efficacy of different therapies of pregnant women or infected neonates. Treatment in pregnancy may be effective since transplacental passage of parasites is delayed. Spiramycin, a complete safe drug which concentrates in the placenta, may reduce the risk of materno-fetal transmission by 60%, but is in the present doses without influence on an already infected fetus. Pyrimethamine in combination with sulfonamides erradicates more effectively parasites in the placenta, and also in the fetus. Today a combination of both regimens is recommended in pregnancy. As for the infected neonates, intensive treatment of pyrimethamine/sulfonamides alternating with spiramycin until one year of age seems to prevent development of late appearing sequelae. There is obviously a need for international multicenter studies to settle the optimal schedules and duration of therapy which again is highly dependent on the performance of an appropriate serological screening during pregnancy.


Prevention of prenatal toxoplasmosis by serological screening of pregnant women in Austria.

In 1975 Austria introduced an obligatory serological screening of pregnant women for toxoplasmosis. Every woman is tested for antibodies at the beginning of her pregnancy and, in case of seronegativity, again in the second and third trimester. Basic tests are--alternatively--Dye test (SFT) and Indirect Fluorescent Antibody test IFAT); for further clarification, complement fixation test (CFT) and, particularly, various tests for detection of specific IgM and IgA antibodies and, in certain cases, for circulating antigen are carried out. If a primary Toxoplasma gondii infection of the pregnant woman is suspected, immediate therapy--with spiramycin before the 16th week of gestation and with pyrimethamin plus sulfadiazin after the 15th week of gestation--is carried out. Before the introduction of the screening programme, the incidence of prenatal toxoplasma infections was 50-70 per 10,000 births, presently it is below 1 per 10,000 births. Seropositivity among pregnant woman has decreased from almost 50% at the end of the seventies, to 36.7% in recent years (1989-1991). The percentage of suspected primary infection during pregnancy has, however, in the same period increased from less than 0.4% to 0.83%.


Screening for toxoplasmosis in pregnant women: presentation of a screening programme in the former "East"-Germany, and the present status in Germany.

The results of the screening programme (including the examination of fetal IgM) in East-Germany, related to the efficiency of therapy (pyrimethamine/sulfonamid) of the fetal infection risk are presented. For comparison the results of a prospective study of toxoplasmosis in pregnancy (n = 1697) without therapy, and follow up of the connatal infected infants to the age of 9/10 years old are shown. Recommendations for the diagnostic and therapeutical management in Germany for the future are presented.


Screening programme for congenital toxoplasmosis in France.

The high prevalence of Toxoplasma gondii infection in France led to the establishment of a national screening programme. Preventive measures were progressively introduced, and these became compulsory in 1978 with the result that the incidence of congenital toxoplasmosis is now markedly reduced. Further improvements may include more systematic sampling from women before pregnancy, better and adequate health education and centralized notification of both maternal and congenital cases of toxoplasmosis.


Cord blood screening for congenital toxoplasmosis: detection and treatment of asymptomatic newborns in Basel, Switzerland.

Cord blood screening is a helpful tool for the detection of infants probably infected with Toxoplasma gondii, if serological data of the mothers are not available. Testing for toxoplasma specific IgM and IgG antibodies of about 30,000 cord blood sera gave information about the changes in prevalence and incidence of toxoplasmosis in pregnant women in Basel between 1983 and 1991. The follow up and treatment of the infected children revealed the need of a randomized study comparing high and low dose treatment schedules.


Choices in preventive strategies: experience with the prevention of congenital toxoplasmosis in The Netherlands.

The control congenital toxoplasmosis mainly relies on preventive measures, that can be applied on an individual basis as well as within the scope of a collective preventive programme. Several strategies can be adopted, each with its possibilities and impossibilities: primary prevention (health education), secondary prevention (serological screening) or a combination of primary and secondary prevention. Whatever strategy is chosen, decisions have to be taken with respect to the procedures. This paper lists the choices to be made and their consequences. The debate in international literature on the desirability of preventive programmes is summarized.


Newborn screening for congenital Toxoplasma infection: five years experience in Massachusetts, USA.

Since 1986, all Massachusetts newborn filter paper blood specimens, and some from New Hampshire, have been screened for the presence of IgM antibodies to Toxoplasma gondii using an enzyme-linked IgM capture assay. Among approximately 530,000 infants screened, 40 had serologically confirmed congenital toxoplasma infection, and 4 additional infants had borderline serologies, for an overall identification and treatment rate of 1:12,000. False positive results from the newborn's filter paper specimen occurred in 22 infants (1/24,000); these were clarified by tests for IgM and IgG in serum specimens obtained 2-3 weeks later from the infant and mother. The screening program would have failed to detect 3 infants with severe infection who were diagnosed on clinical grounds prenatally or at birth and lacked IgM. No infants with a later diagnosis of congenital toxoplasmosis that was missed by screening are known to our statewide network of pediatric infectious disease consultants. Follow-up studies are in progress to evaluate more completely the sensitivity of the IgM assay in newborns and the efficacy of treatment.


Epidemiology of toxoplasmosis in the U.K.

The overall rate of toxoplasma infection in the U.K. is between 23-33% though there is evidence of regional variation. Seropositivity increases by 0.5-1.0% per annum to reach about 50% at the age of 60 years. The incidence of acute infection in pregnant women is about 2-2.6% per thousand pregnancies while the transplacental transmission rate is reported to range from 0% to 40%. As there is no official notification of congenital toxoplasma infections within U.K. the true number of cases is not known. However, information relating to the prevalence of infection in the general population in the U.K. is outdated and new studies are urgently required.


The program for antenatal screening of toxoplasmosis in Finland: a prospective cohort study.

16,733 pregnant women were studied for toxoplasma specific antibodies during an 18-month period. The number of specimens was 44,181. The IgG seropositivity of mothers was 20.3%. The incidence of primary toxoplasma infections during pregnancy was 4.2 per 1000 seronegative pregnancies by using the traditional criteria, IgG seroconversion and/or a positive IgM. By using the IgG activity test as an additional criterion, the incidence was 2.4 per 1000 seronegative pregnancies. Due to transmission rate of 40%, the number of congenital toxoplasma infections in Finland is more than 50 per year. The evaluation is going on and the cost-benefit analysis will reveal the effectiveness of antenatal screening.


Neonatal screening for congenital toxoplasmosis in Denmark: presentation of the design of a prospective study.

The design of a two year prospective study of 45,000 mothers and their newborn children aiming at determining the incidence of congenital toxoplasmosis in Denmark is presented. Toxoplasma IgG antibodies in a bloodspot from the newborn, routinely collected on filterpaper (the Guthrie card), and IgG antibodies in a stored serum sample from the mother collected in the first trimester are compared. Seroconversion identify mothers infected with T. gondii during pregnancy and identify newborn children at risk of congenital toxoplasmosis. All children at risk will be treated and followed until congenital toxoplasmosis is verified or excluded. Children with verified congenital toxoplasmosis will be followed clinically and the effectiveness of the treatment will be evaluated. The study design allows determination of the materno-fetal transmission rate in untreated pregnancies, and will furthermore allow a good estimate of the incidence of congenital toxoplasmosis in Denmark. In addition we hope that the diagnosis and treatment of cases of subclinical toxoplasmosis will prevent chorioretinitis and minor cerebral disorders later in life. Of 6355 pregnancies tested during the first 3 month of the study, 14 cases of maternal seroconversions have been diagnosed. Only one child had detectable toxoplasma specific IgM antibodies at birth.


Current status of toxoplasmosis in pregnancy in Norway.

The paper reports previous epidemiologic data obtained in Norway and describes briefly the design of a prospective study of primary toxoplasma infection which will be carried out among pregnant women in Norway in the period 1992-1994.


Twenty-two years screening for toxoplasmosis in pregnancy: Liege-Belgium.

Between 1966 and 1987, in Liége--Belgium, 20,901 pregnant women were screened for toxoplasmosis. In this period an increase in seronegative women from 30% to 53% and a decrease in the seroconversion rate from 6.4% to 1.2% was observed. This decrease could be the result of advice and prophylactic measures. Due to the low rate of seroconversion (actually less than 1%), the cost/effectiveness of a systematic screening and fetal diagnosis should be investigated.


Economic evaluation of preventive programmes against congenital toxoplasmosis.

Benefit-cost analysis are applied to different strategies aimed at preventing congenital toxoplasmosis. The first strategy involves health education of pregnant women on how to avoid toxoplasma infection. The second strategy comprise serological surveillance in pregnancy combined with prenatal diagnosis and chemotherapy. The cost of health education is less than the cost of the serological screening, but health education will most likely lead to a haphazard testing of individuals and thereby increasing the cost. The best and most rational approach, and the programme which will prevent most cases and save most money for the society, is a combination of both programmes. Compared with the results of any of the two strategies alone, the benefits of the combined programme will increase significantly, while the cost (NOK 165 per participating woman) will only add fractions to that of the serological screening programme. The benefits of the strategies are influenced by many uncertain factors such as the discount rate, the incidence of infection, the intrauterine transmission rate, the outcome of pregnancy, the prognosis of the offspring, the sensitivity of the screening tests and the effectiveness of the programme. After applying a sensitivity analysis, both programmes were found to be of economic benefit to society at an incidence of maternal toxoplasmosis of 1-1.5 per 1000. Thus the pilot screening initiated in Norway to determine the incidence of infection, seems justified.


Intravesical instillation of drugs in patients with detrusor hyperactivity.

Intravesical administration of drugs may inhibit detrusor hyperactivity. Intravesical drug administration might be clinically useful in patients with detrusor hyperactivity, particularly in patients with neurogenic etiology using CIC. The therapeutic usefulness has to be documented in controlled studies. The mechanisms of action and the potency of the individual substances can not be decided from the present investigations. However, no finding contradicts that the known pharmacological properties of the drugs used are responsible for the effects noted. The different responsiveness to intravesical drugs between patients with neurogenic and non-neurogenic etiology might be due to pathophysiological differences. By intravesical administration of drugs the tissue concentration obtainable within the bladder wall is higher than the one obtainable by systemic administration. The optimal relation between tissue and serum concentrations can be achieved by a careful preparation of the drug solution and by titration of the dose. No side effects were found in the studies and no clinically significant side effects have been reported by other investigators. The risk of late side effects is unknown. The serum concentrations found in man and rabbit, after intravesical instillation of terodiline, indicate that by this route of administration terodiline may be safely used, in spite of the side effects reported at systemic administration. For evaluation of the diagnostic usefulness further documentation of the mechanisms of action and of the pathophysiology are needed.


[Ultrasonic diagnosis of bile duct calculi. A prospective study regarding the effects and the objective and subjective factors on accuracy in choledocholithiasis].

The reliability and diagnostic sensitivity of the sonographic identification of bile duct concrements is mainly determined by the examiner's competence and the size of the concrements, and secondly also by the diameter or patency of the bile ducts. Basing on the records of 175 patients on whom choledocholithiasis had been performed, a prospective study (reference: concrement removal after ERCP) showed that the sensitivity of the method is almost twice as high with an experienced examiner than with a less experienced physician (80% vs. 47%). In 231 other cases with extrahepatically conditioned cholestasis we found a 93% specificity of sonography in respect of excluding the presence of concrements. 93% of the concrements that were bigger than 10 mm were definitely diagnosed via sonography (71% sensitivity in case of concrements < 10 mm). If the proof of presence of concrements is differentiated according to bile duct width, it is seen that 85% of all concrements were visualised if the width of the ductus choledochus was > or = 8 mm and 71% in case of a width < 8 mm. The results of the study justify the use of sonography as a primary method in the diagnosis of concrements of the bile ducts; under certain conditions it is also possible to exclude the presence of stones. If findings do not agree with the clinical pattern of findings, or if the bile ducts cannot be visualised properly, diagnostic ERCP is indicated.


[Sonography and biliary extracorporeal shockwave lithotripsy (ESWL)].

Ultrasound is an indispensable tool for preliminary diagnosis ("filter function"), during treatment ("monitoring function") and in the follow-up examinations ("follow-up function") after shock-wave lithotripsy of gallstones. It permits rapid and reliable assessment of the therapeutic outcome and early identification of complications, which present-day experience has shown to be rare.


[Endosonography in chronic pancreatitis. A comparative study of endoscopic retrograde pancreatography and endoscopic sonography].

EUS and ERP were performed in 114 patients. 94 patients (32 women, 62 men; mean age 53 years; range 29-78 years) had inflammatory pancreatic disease while 20 patients (6 women, 14 men; mean age 54 years; range 28-78 years) without disease of the pancreas served as controls. ERP-findings served as the gold standard and were classified into stages I-III according to the Cambridge classification. On ERP 51 patients had duct changes typical of chronic pancreatitis (CP). Control cases always displayed a homogeneous echo pattern and a regular outer margin of the pancreas. Abnormal EUS findings were present in all patients with ERP-stages II and III and in 88% of patients with ERP-stage I. 63% of patients with a normal pancreatogram, i.e. ERP-stage 0 showed pathological alterations on EUS examination. Diffuse alterations of the echopattern were seen in 75% of CP patients with stage I, in 88% with stage II and in 96% with stage III. Alternating echo-poor/echo-dense areas were present in 50% of stage I, in 88% of stage II, and in 81% of stage III cases, respectively. 38% of stage I, 56% of stage II, and 27% of stage III cases displayed a lobulated appearance of pancreatic parenchyma. In 80% of the patients these findings were combined with an irregularly lined pancreatic surface. This same combination of EUS-findings in proven CP was also present in 30% of patients with completely normal pancreatic ducts, i.e. ERP-stage 0. Changes of the main pancreatic duct in stages II and III were also seen with EUS in 81% and 96%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


[Value of duplex sonography in diagnosis of renal artery stenosis and its value in follow-up after angioplasty (PTA)].

The assessment of the renal arteries is particularly important in the detection of a renovascular cause of the arterial hypertension. The purpose of the present study was twofold: to evaluate the accuracy of duplex scanning in non-invasively diagnosing renal artery stenoses in hypertensive patients, and to determine the results of transluminal angioplasty of renal artery stenoses as assessed by duplex scanning. In 76 patients with arterial hyertension, 170 renal arteries (18 kidneys supplied by two renal arteries) were examined by both duplex scanning and angiography (DSA in intraarterial and intravenous technique, and conventional arteriography). Peak systolic and end-diastolic flow velocity parameters as well as the Pourcelot-index were determined in the proximal renal artery and compared with the indendently performed angiography. In 102 angiographically proven normal renal arteries, mean +/- SD peak systolic and end-diastolic velocity values were 84.7 +/- 13.9 cm/s and 31.2 +/- 7.8 cm/s, respectively, with a Pourcelot-index of 0.66 +/- 0.07. For detecting renal artery stenoses greater than 50%, duplex scanning had a sensitivity of 86%, and a specificity of 83% for a systolic peak velocity of 140 cm/s and more in the renal artery. In 13 patients with 14 stenosed renal arteries, duplex scanning and intraarterial DSA densitometry were performed before and after transluminal angioplasty of the renal artery stenoses. There was fairly good agreement between transstenotic peak systolic velocities and densitometrically determined degrees of stenosis in the renal artery (r = 0.84). These results show that duplex scanning is an accurate noninvasive diagnostic tool in detecting proximal renal artery stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)


[Pulsatile flow model with elastic blood vessels for duplex ultrasound studies].

Using ultrasound duplex technique flow phenomena in patients' circulation can be examined. For the interpretation of these examinations it is necessary to have extensive knowledge on flow influencing parameters. This can be easily obtained from simplified flow models. This article describes the components of a flow model that allows examination of ultrasonic contrast media flowing through an artificial heart and vessel mimicking tubes. The artificial heart is the drive which pumps a water glycerol cellulose mixture through the circulation in a pulsatile manner. The shape of the ventricle, the compliance of the aorta, the viscosity of the flow medium and the wall elasticity of the examination vessel were taken into account. The attenuation caused by the surrounding tissue is simulated by a variable layer of castor oil. The flow model is suitable to produce flow profiles that are very similar to physiological profiles.


[Written documentation of ultrasound findings. A contribution to rationalization and standardization: how should a report of ultrasound findings be organized?].

A system for documentation of ultrasonographic findings is presented. Characteristic items and features of a report are defined.


[Ultrasonic diagnosis of goiter of the tongue base].

Lingual goitre was found in two adolescents suffering from mild dysphagia. Since there were typical changes in lingual sonomorphology, sonographic evaluation was easy to perform. Lingual thyroid was less echogenic than normal thyroid tissue. Ultrasound may support the decision of the initial treatment and is useful to guide further therapy.


[Ultrasonic diagnosis of so-called "occult" testicular tumor].

A 40-year old man complaining of severe pain in the right mid-abdomen, nausea and vomiting was brought to the casualty department. Sonography revealed retroperitoneal masses in the right mid-abdomen and the left lower abdomen. These masses were confirmed by computed tomography and lymphography to be lymph node metastases. In the smaller right testis, in which a tumour was not suspected, a hypoechoic region was identified, which on histological examination after orchiectomy proved to be a pure seminoma.


Anatomic basis of pronator quadratus flap.

The pronator quadratus m. can be raised as a flap on its main anterior interosseous pedicle, whose characteristics are as follows: diameter of the artery 2.1 mm, diameter of the each of both veins 2.4 mm, length of useful pedicle 70-80 mm, after possible intraneural dissection of the nerves to the flexor pollicis longus m.


Preparation of four-color arterial corrosion casts of the laryngeal arteries.

The supply areas of the superior and inferior laryngeal arteries were studied in order to plan tissue-sparing laryngeal surgery. Arterial corrosion casts with and without preservation of the laryngeal skeleton were prepared and the supply areas of the superior and inferior laryngeal arteries were distinguished from each other by injecting differently colored methacrylates. The ramifications of the laryngeal arteries could be classified clearly in the macerated specimens which preserved the laryngeal skeleton.


Rotation-abduction analysis in 10 normal and 20 pathologic shoulders. Elite system application.

Kinematics of shoulder rotation-abduction in the plane of the scapula were analysed using the Elite system. We evaluated 10 asymptomatic subjects and 20 patients with painful conditions affecting the shoulder, 10 adhesive capsulitis and 10 rotator cuff-tears. The last pathologic cases were reexamined after rehabilitation treatment. The Elite system computed on line the trajectories of 8 retro reflective markers glued on the main reference points (3 on the spine, 3 on the scapula and 2 on the humerus). Angles and linear velocities were also evaluated. The lower humeral site displacement and gleno-humeral angle increase allowed differentiation of the normal shoulder rotation-abduction from the abnormal movement. Hence, rehabilitation progress could be followed up.


Growth of the human metatarsal bones in the fetal period (13-24 weeks postconception): a quantitative study.

We studied metatarsal growth in 600 metatarsal bones (60 pairs of feet) taken from 60 human fetuses (35 males and 25 females) ranging in age from 13 to 24 weeks postconception. The data obtained for the total length (TL) and for the ossified metatarsal length (OML) were correlated to fetal crown-rump length (C-R). The ossified metatarsal length presented a growth rate greater than the total length growth rate. There was no statistical difference between either the right and left metatarsals or males and females in total length and ossified metatarsal length growth during the period studied. We believe that metatarsal growth curves could be used to monitor fetal foot growth.


The ramification of the superficial branch of the superior gluteal artery. Anatomical basis of a new gluteus maximus myocutaneous flap.

In order to design a new gluteus maximus myocutaneous flap, the ramification of the superficial branch of the superior gluteal artery was investigated in 56 sides of 33 Japanese cadavers. The superficial branch constantly divides into two main branches, which are called the ascending and transverse branches in this study. Of the ascending and transverse branches, one or both usually give off at least one well developed division running on the undersurface of the gluteus maximus muscle (98.2%). This division, which is called the intermediate branch in this study, generally reaches the superior edge of the muscle giving off only a couple of muscular branches and pierces the muscle and its deep fascia to supply skin (83.6%). Perforators of the intermediate branch constantly emerge from the fascia near the middle or lower one-third point on a line extending from the middle of the iliac crest to the tip of the greater trochanter.


The thenar muscles. New findings.

Examination of the thenar muscles in 30 anatomical preparations of the hand have shown that the abductor pollicis brevis, the opponens pollicis, and the adductor pollicis muscles are made up of several muscle bellies. The number and insertions of these bellies are varied. Both heads of flexor pollicis brevis do not originate from any particular muscle belly. The superficial head of this muscle always inserted into the head of the thumb metacarpal, either completely, or, some of the fibres of the dorsal aponeurosis of the thumb were attached to the base of the proximal phalanx. Furthermore the anatomy of the abductor pollicis brevis muscle was related to the presence of a tendinous slip from abductor pollicis longus. These variations could have an influence on proprioception in the thumb ray.


Fascial layers of the scalp. A study of 48 cadaveric dissections.

The arrangement and structure of the fascial layers of the scalp were studied in 48 red neoprene latex-injected cadavers with the aid of an operating microscope. The galea aponeurotica was continuous with a superficial temporal fascia. Deep to the galea, the subaponeurotic connective tissue was bilaminar. There was an outer, vascular, areolar layer, and an inner, avascular, membranous layer. Underlying the temporalis muscle, the pericranium was thinner and more adherent than elsewhere with no subpericranial tissue.


Radiologic anatomy of the paranasal sinuses in the child.

The development of the paranasal or accessory sinuses begins very early in utero. In the newborn the ethmoidal sinus, which gives rise to all the other sinuses, as well as the maxillary sinus, can already be identified on x-rays. The frontal sinus appears as a triangle at the age of four and oversteps the supraorbital margin at the age of six. The sphenoidal sinus begins to excavate the concha sphenoidalis at the age of four and can be seen on x-rays at the age of eight, when it extends to the hypophyseal fossa. In the twelve-year-old child all sinuses almost reach their final sizes. However, the size and shape of all sinuses, particularly of the frontal and the sphenoidal sinuses are very different.


Bi- and three-dimensional CT study of carpal bone motion occurring in lateral deviation.

A computed tomography (CT) study of the right wrists of 15 volunteers and of 5 anatomical preparations in neutral position, radial (15 degrees) and ulnar (30 degrees) deviation enables to tackle the qualitative analysis of carpal bone motion. The CT Scans were analyzed and reconstructed in three dimensions by means of the Philips CAMRA S100 computer program. The results show that the capitate, the metacarpals II and III and, to a lesser extent, the trapezium and the trapezoid are poorly mobile. Our study points to the role of the flexor and extensor carpi ulnaris muscles in the stability of the internal carpus, confirming that the pisiform is a sesamoid bone in the flexor carpi ulnaris tendon. A model of longitudinal functional structure of the carpus during lateral deviation, intermediate between those of Navarro and Taleisnik, is proposed.


High resolution MRI of the normal finger at 0.1 T: anatomic correlations.

MR images of the fingers are obtained in a 128 x 128 or 256 x 256 matrix format using a prototype of a mini imager dedicated to the hand. The vertical field of 0.1 T is provided by an electro-magnet with an air gap of 15 cm equipped with a single solenoidal coil. No Faraday cage is used. The maximum in plane pixel resolution of 100 mu is obtained for a field of view of 2.5 cm with a slice thickness of 2 mm. The identification of fine structures of the finger is demonstrated by the anatomical and histological correlations. This type of imager which is adapted to very limited field of views demonstrate that high resolution MRI of limb extremities can be achieved at 0.1 T.


Retroaortic left renal vein: a report of six cases.

Six cases of retroaortic left renal vein have been studied, two in corpses and four by means of Computed Tomography. Any previous pathology has been rejected. The total number of dissected specimens was 116, whereas the patients with non-pathological retroperitoneum studied by CT numbered 170. In our six cases, the left renal vein formed a single trunk of considerable size, retroaortic position and directed obliquely towards the inferior vena cava.


Avian model for 13-cis-retinoic acid embryopathy: morphological characterization of ventricular septal defects.

In developing an avian model for 13-cis-retinoic acid (13cisRA) embryopathy, we found 13cisRA induced cardiovascular defects, especially Type I ventricular septal defects (VSDs) (Hart et al.: Teratology 41:463-472, '90). As the first step of investigating possible mechanisms, we have examined the light microscopic morphology of RA-induced cardiovascular defects in chick embryos. Fertilized eggs were injected via yolk sac with 150 micrograms 13cisRA in dimethylsulfoxide (DMSO), DMSO or mock injection on embryonic day 5 (E5). On E6, E7, or E8, surviving embryos were sacrificed and fixed in 10% formalin. Thoracic blocks were exised, embedded in paraffin and serially sectioned through the heart, base to apex. Slides were stained, screened for tissue orientation, then coded and evaluated without knowledge of treatment group. Examination of serial sections permitted qualitative evaluation of conotruncal ridge volume, mesenchymal organization, necrosis and extent of fusion. Extent of fusion was the only parameter influenced by 13cisRA treatment. On E6, ridge fusion was incomplete in all groups at comparable levels. On E7, ridge fusion in 13cisRA-treated embryos had not progressed as far proximally as in controls. By E8, there was a significant difference in the extent of fusion between 13cisRA-treated and non-RA-treated groups. We conclude 13cisRA-induced VSDs resulted from defective conotruncal ridge fusion and that the fusion defects did not result from decreased tissue volume, altered mesenchymal organization or increased necrosis.


Abnormalities in ureter and kidney development in mice given acetazolamide-amiloride or dimethadione (DMO) during embryogenesis.

These experiments more accurately define the effects of the combination acetazolamide-amiloride or a single dose of dimethadione (DMO), the active metabolite of trimethadione, on the development of the ureter. When acetazolamide-amiloride was administered in C57BL/6NCrlBR mice on day 9, 9.5, or 10 of gestation (plug = day 0) a second ureter was formed, anterior to the original ureter, inducing a second kidney. The second ureter then fails to make a connection with the developing bladder and remains attached to the mesonephric duct. The mesonephric duct becomes the vas deferens in the male and deteriorates completely in the female leading to either a restricted ureter or a blocked ureter depending on the sex of the fetus. Administration of a single dose of DMO between gestational day 9 and 10.3 produced both renal agenesis and ureters of varying lengths. Some ureters were of normal length with a tuft of one or two nephrons at their tip, while others were one half or one quarter of their normal length. In some instances the ureter was completely absent. The reason for this strong effect on the ureter is unknown.


Clinical anophthalmia: an epidemiological study in northeast Italy based on 368,256 consecutive births.

We describe an epidemiological and clinical study of Clinical Anophthalmia in a population of consecutive live and stillborns enrolled in a hospital based registry of congenital malformations in Northeast Italy during the period from 1981 to 1989; 22 cases were detected among 368,256 births yielding a birth prevalence of 0.60 per 10,000 (95% CI 0.34-0.84); 20 cases were associated with at least one other major malformation. Malformation syndrome, association, or sequence was diagnosed in 13, while a non-recognizable multiple defect pattern was observed in 7/20 (35%). A chromosomal anomaly was present in eight syndromic cases. No significant trend over time, nor space or time clusters, were detected. As most CAn cases are associated with other anomalies recognizable by ultrasound, a decreasing trend in its prevalence at birth is expected in the future.


A population-based study of congenital diaphragmatic hernia.

From 1983 through 1987, in a California population of 718,208 births, 237 infants were born with a congenital diaphragmatic hernia (CDH), a birth prevalence of 3.30 per 10,000 total births (live births and stillbirths). We proposed that the various types of this defect, characterized by their different pathogeneses, would be reflected in differences in their descriptive epidemiologies. We evaluated various demographic, maternal, and infant characteristics for three major types of defects, the Morgagni hernia, the pars sternalis hernia, and the posterolateral hernia, categorizing the latter type into isolated defect (N = 129), multiple congenital anomalies including nonchromosomal syndromes (N = 86), trisomies (N = 10), and chromosomal anomalies other than trisomies (N = 2). For the posterolateral hernia, we present the distribution of associated anomalies (43%) and specifically of midline defects (19%). Although the number of cases for the Morgagni hernia (N = 5) and the pars sternalis hernia (N = 5) were small, comparisons with the posterolateral hernia suggested lower sex ratios, of borderline significance for the pars sternalis hernia (P < 0.09), and higher mean maternal ages for both groups. Within the posterolateral type, we found a significantly higher male to female ratio (M/F = 1.58) only for the isolated subgroup compared to the population (P < 0.03), and a borderline significant rural/urban difference in prevalences (2.12 vs. 1.45 per 10,000) (P < 0.06). Additionally, the distribution of monthly prevalence rates adjusted for gestational age suggested opposite seasonal trends between the isolated and the other posterolateral hernias; within this latter subgroup the difference between the highest monthly rate (1.68) and the lowest (0.96) was of borderline significance (P < 0.09). Our results suggest the need to consider the respective types and subgroups of CDH separately in epidemiologic studies.


The perception of teratogenic risk of cocaine.

While there has been a substantial increase in recreational use of cocaine by young adults, conclusive evidence for cocaine teratogenicity in humans is lacking, and even those believing the drug is teratogenic agree that the rates are quite small. While counseling pregnant women on their teratogenic risk, it was our impression that there is an unrealistically high perception of reproductive risk of cocaine. We wished to quantify the perception of teratogenic risk of cocaine by the public, physicians, and by pregnant women who were counseled following gestational exposure to the drug. Women taking cocaine during the first trimester of pregnancy (n = 54), controls with post secondary education (n = 30), and physicians (n = 30) were asked, using a visual analogue scale, to quantify the teratogenic risk of cocaine and the tendency to terminate/continue the pregnancy after first trimester exposure; in the case of the "public" and physicians this was a hypothetical question. Both physicians and the controls perceived cocaine to be teratogenic (13.4 +/- 11% risk of major malformations by physicians, and 56.5 +/- 22.8% by the "public"). The controls believed cocaine to be as hazardous as thalidomide (57.2 +/- 25.6% risk for thalidomide). Asked whether they would wish to terminate such pregnancy in their family, most physicians (56%) and the controls (70%) had a greater than 50% tendency to terminate.(ABSTRACT TRUNCATED AT 250 WORDS)


Process of building biologically based dose-response models for developmental defects.

The problem of developing biologically-based dose-response models is addressed for predicting the prevalence of birth defects at low doses of toxic chemicals administered during pregnancy. To illustrate the process of incorporating biological information, a model is postulated to predict the prevalence of cleft palate for a chemical that reduces embryonic/fetal growth, which results in inadequate palatal cells for closure. Experimental bioassay data examining the prevalence of cleft palate in mice exposed to the herbicide 2,4,5-T are used to illustrate the process. With the limited data available, it is necessary to assume a model for cell growth and the relationship between the cell growth rate parameter and dose of 2,4,5-T. Also, a relationship between cleft palate prevalence and growth is assumed and then checked with experimental data. The purpose of the paper is not to provide a universal biologically based dose-response model for cleft palate, but rather to demonstrate the extent, and type of information and data required. It remains to be seen if the form of the model is appropriate for chemicals that primarily produce embryo/fetal malformations or death via reduced or delayed cellular growth.


Lens and mesenchyme ultrastructure in gestational day 11 trisomy 1 mice.

The lenses and head mesenchyme of two 11-gestational day trisomy 1 mouse embryos and a normal littermate were examined using transmission electron microscopy (TEM). One trisomic embryo had a small lens with a lens stalk; the other was aphakic. The resolution available with TEM allowed detailed evaluation of cell organelles, spatial relationships and the intra- and extracellular structural environment of the lens and head mesenchyme in normal and aneuploid embryos. Differences in fine structure between normal and trisomic lenses included (1) type of epithelium, (2) size of intercellular lacunae, and (3) activity of Golgi complexes. Differences in mesenchyme included (1) the number and size of cytoplasmic extensions, (2) shape of the cells, and (3) reduced endotheliomesenchymal interactions.


Neural tube defects without neural crest defects in splotch mice.

Homozygous Splotch mutant mice (Sp/Sp) die on day 14 of gestation with neural tube defects, curly tail, and malformations of neural crest derivatives. Sp1H mice, which have a radiation-induced allele of Splotch with a similar phenotype, were used for this study. The neural tube defects are always located in the lumbosacral region and in 50% of the cases also in the region of the hindbrain. In this report, rare cases of neural tube defects and tail defects among the offspring of crosses between Splotch (Sp1H) heterozygotes are presented, which are not associated with a neural crest defect. This suggests that the development of the neural tube and neural crest defects in this mutant is caused by independent mechanisms or is dependent on the dosage of the mutant gene, with different thresholds being pathogenetic in the neural tube and neural crest, respectively.


Craniometric measurements of craniofacial malformations in the X-linked hypophosphatemic (Hyp) mouse on two different genetic backgrounds: C57BL/6J and B6C3H.

This study reports data on craniometric measurements in the X-linked hypophosphatemic (Hyp) mouse on two different genetic backgrounds: C57BL/6J and B6C3H. Heads of normal females "+/+," normal males "+/Y," heterozygous mutant females "Hyp/+," and hemizygous mutant males "Hyp/Y" for each genetic background were examined. Data were collected via skull measurements. On a C57BL/6J background, the neurocranium of mutants "Hyp/+" and "Hyp/Y" was shorter and slightly higher than in normal counterparts. On a B6C3H background, mutant mice "Hyp/+" and "Hyp/Y" were shorter in neurocranial length than in normal counterparts. Viscerocranial height was larger in "Hyp/Y" than in normal counterparts. No differences in neurocranial and mandibular height were found. Mutant mice on a C57BL/6J background were compared to mutant mice on a B6C3H background. No differences in neurocranial length were found. Cranial length was shorter in "Hyp/Y" on C57BL/6J than in "Hyp/+" on B6C3H. Facial length parameters were shorter in "Hyp/Y" on C57BL/6J than in "Hyp/Y" and "Hyp/+" mutant mice on B6C3H. Mandibular length was shorter in "Hyp/Y" on C57BL/6J than in "Hyp/+" on C57BL/6J and both mutant mice ("Hyp/Y" and "Hyp/+") on a B6C3H background. The results of this study indicate that craniofacial growth is less affected in mutant mice on a B6C3H genetic background than in mutant mice on a C57BL/6J genetic background.


Preferred use of primary radiolabeled anti-platelet monoclonal antibodies. Comparison of immunoblotting methods for the analysis of functional domains on human platelets.

Several methodologies used for the identification and characterization of platelet receptors for antiplatelet monoclonal antibodies are compared. Two antiplatelet monoclonal antibodies, are investigated due to their potent effects on human platelet function. A platelet-activating monoclonal antibody, called M.Ab.F11, is able to induce platelet aggregation and granular secretion. A platelet-inhibitory monoclonal antibody, named G10, strongly blocks the platelet aggregation and granular secretion induced by M.Ab.F11, as well as by physiological agonists. In order to identify the specific antigens recognized by these monoclonal antibodies, we tested a number of immunostaining methods. Comparison of various procedures revealed that a high degree of nonspecific interactions with platelet proteins occurred when the commonly used secondary reagents, protein A and radiolabeled or enzyme-conjugated secondary antibodies interacted with the platelet proteins either in the presence or absence of primary monoclonal antibodies. On the other hand, we observed a high degree of specificity and selectivity when only radiolabeled anti-platelet monoclonal antibodies were used as single reagents. It is established that M.Ab.F11 interacts with the platelet membrane proteins of 32 and 35 Kd, and M.Ab.G10 recognizes 100 Kd protein, which corresponds to GPIIIa molecule.


Collagen-induced rat platelet reactivity is enhanced in whole blood in both the presence and absence of dense granule secretion.

Collagen induced aggregation, ATP secretion and thromboxane (TxB2) generation of storage pool deficient platelets were compared to normal platelets of closely related rat strains. Platelet function was monitored in citrated-platelet-rich-plasma (PRP) and citrated whole blood. Wistar (W) and fawn-hooded (FH) rat strains and their F2 hybrids were utilized. The W strain, which is ancestral to the FH strain, is not storage pool deficient while the FH strain is. This was manifested by the total lack of collagen induced ATP secretion from platelets of the FH strain while the platelets of the W strain secreted normally. Utilizing platelets from the F2 generation of WxFH matings, the absence of dense granule secretion (ATP) from the FH platelets, as well as other platelet defects of FH rats, were shown to be associated with homozygosity for the red-eyed dilution gene [r]. The non-secreting FH platelets were utilized to determine the effects of secreted dense granule constituents upon collagen induced aggregation and TxB2 generation. The non-secreting storage pool deficient platelets did aggregate and did generate TxB2 upon stimulation with collagen; however, the storage pool deficient FH platelets demonstrated less TxB2 generation and did not aggregate as effectively as the normally secreting platelets of the W strain. When evaluating collagen induced platelet function in whole blood as compared to PRP, the storage pool deficient platelets remained less reactive than normally secreting platelets, but both platelet types demonstrated enhanced aggregation and increased TxB2 generation in whole blood.


Thrombosis in spinal cord injury.

Some traditional coagulation assays and several new molecular markers of hemostatic activation were measured in 37 patients with spinal cord injury (SCI). Twenty one of the patients (57%) developed deep vein thrombosis (DVT). The radiofibrinogen uptake test (RFUT) was used to diagnose DVT. Thirty eight percent of quadriplegic and 88% of paraplegic patients developed DVT (p < 0.005). No significant differences were found in platelet counts, mean platelet volumes, fibrinogen levels, von Willebrand factor (Ag) levels, platelet factor 4 and beta thromboglobulin concentrations between the groups with and without DVT. Fibrinopeptide A, thrombin/antithrombin III (TAT) complexes and plasma D-dimer levels were significantly higher in the patients with thrombosis. Most patients with DVT had elevated TAT complex levels up to three days before the RFUT became positive. D-dimer levels were highest after the diagnosis had been made.


Bacterial expression, purification, and partial characterization of amino acids 94-155 of human tissue factor pathway inhibitor (TFPI) as an inhibitor of blood coagulation factor Xa.

Tissue factor pathway inhibitor (TFPI) is a plasma-derived protein which inhibits two of the active serine proteases present during normal blood coagulation. Inhibition of both of these proteases, factors VIIa and Xa, is thought to require a factor Xa-TFPI complex. To begin to investigate the interactions between factor Xa and TFPI, amino acids 94-155, which encode for the second Kunitz domain (K2) of TFPI, were expressed, purified, and partially characterized. Expression of the recombinant peptide was accomplished using an E. coli expression system which produced the peptide at an expression level of approximately 2-5% of total cell protein. The peptide was localized to disulfide-linked refractile bodies which were solubilized by reduction in the presence of denaturant and the soluble protein refolded. Oxidized K2 was purified from the refold mixture using a two-step procedure employing gel filtration chromatography and reverse-phase HPLC. The unprocessed form of the recombinant peptide, Met-Ala-K2 (rMA-K2), was characterized. This peptide was purified to apparent homogeneity as determined by SDS-PAGE, quantitative amino acid, Edman degradation, and electrospray mass spectrometry analyses (> 95% pure). The product bound to factor Xa covalently coupled to a solid support in the presence of 2M sodium chloride demonstrating its affinity for this enzyme. Preincubation of rMA-K2 peptide with factor Xa neutralized, with 1.1:1 stoichiometry, the ability of factor Xa to hydrolyze a small chromogenic substrate. Additionally, rMA-K2 prolonged the time to clot formation in a plasma-based assay dependent on factor Xa concentration. Finally, this peptide mildly prolonged the prothrombin and modified prothrombin times of normal pooled plasma. Taken together this data demonstrates that this region of TFPI inhibits factor Xa activity and allows for further characterization of this enzyme-inhibitor complex.


The effect of dietary n-3 fatty acids on in vivo platelet aggregation in the cerebral microcirculation.

Diets enriched in n-3 fish oil have been suggested to decrease coronary artery disease in part through their ability to decrease cyclooxygenase-dependent platelet aggregation. However little is known concerning the effect of n-3 fatty acids on in vivo platelet aggregation. The purpose of these experiments was to determine whether dietary n-3 fatty acids affect the rate at which platelet aggregation occurs in cerebral arterioles. Fish oil (200 mg eicosapentaenoic acid + 143 mg docosahexaenoic acid/kg), corn oil or water was given daily by gavage to mice (n = 30) for six weeks and then in vivo platelet aggregation was induced by the light plus dye method, which injuries the endothelium. Two additional groups of mice were acutely treated with saline or indomethacin (0.5 mg/kg, ip), with the latter serving as a positive control for therapeutic inhibition of platelet aggregation. Serum thromboxane B2 was analyzed by RIA. All fed groups gained weight equally. Serum thromboxane B2 was decreased by 40% in the fish oil group (p = 0.05 vs. corn oil, p = 0.07 vs. water). The mean (+/- SE) time to first aggregate in pial arterioles was 101 +/- 6, 91 +/- 6 and 101 +/- 9 seconds in the fish corn oil and water groups, respectively. Indomethacin significantly increased the time to first arteriolar aggregate by 35% (p < 0.002) and caused an 80% reduction in serum thromboxane. These studies show dietary fish oil produces a moderate reduction in serum TxB2 level and does not affect arteriolar platelet aggregation whereas indomethacin produces a drastic TxB2 reduction and significantly slows platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)


Intraplatelet von Willebrand factor and ABO blood group.

Levels of plasma Von Willebrand Factor (vWF) are known to be influenced by ABO Blood Group but such an influence on platelet vWF is not known. Forty-three healthy donors had blood drawn for measurement of plasma and platelet vWF, both antigenic (vWF:Ag) and functional (RCo). Twenty-six were Group O and seventeen were Group A. Groups did not differ in age, platelet count, hemoglobin, white cell counts, platelet rich plasma counts nor length of in vitro storage of samples prior to assay. Plasma levels of vWF:Ag and RCo was lower in Group O as expected. Platelet RCo was lower in Group O and such a trend was present for vWF:Ag. This influence of ABO Groups on platelet vWF was modest compared to that on plasma vWF.


Dibucaine elicits platelet procoagulant activity in factor VIII and factor X activation by a mechanism involving a sulfhydryl-dependent enzyme.

Dibucaine, a potent inhibitor of platelet aggregation and platelet release, was found to enhance the ability of fresh gel-filtered or washed human platelets to support factor VIII activation and factor X activation. Dibucaine-treated platelets increased the peak of factor VIII clotting activity by 2-fold compared to activity with untreated platelets. Similarly platelets optimally stimulated by dibucaine (1.0-1.5 mM for 5 min at 37 degrees C) supported as much factor X activation by factors IXa and VIII (measured in a chromogenic assay) as platelets optimally stimulated by ionophore A23187 (15 microM). An assay of platelet calcium-dependent sulfhydryl proteases was devised and used to test the effect of various inhibitors on these platelet proteases. The membrane-permeable sulfhydryl inhibitor Thiolyte MB inhibited platelet calcium-dependent protease activity; whereas, membrane-impermeable Thiolyte MQ did not. Thiolyte MB also blocked the ability of dibucaine-stimulated platelets to support factor X activation. Incubation of fresh, gel-filtered platelets with calpain inhibitor II (N-Ac-L-L-Normethioninal) completely inhibited the calcium-dependent sulfhydryl protease activity of these platelets but did not affect their ability to support factor X activation after subsequent incubation with dibucaine. These data support the interpretation that an intracellular SH-dependent enzyme, which may not be calpain, is involved in the expression of platelet procoagulant activity in dibucaine-treated platelets.


Antithrombin III supplementation during orthotopic liver transplantation in cirrhotic patients: a randomized trial.

Severe intraoperative bleeding is one of the main problems during liver transplantation. Acquired hemostatic defects, namely primary or secondary hyperfibrinolysis, are considered significant pathogenetic events. Antithrombin III (ATIII), the main physiological serine protease inhibitor, has a critical role in the regulation of hemostasis. 29 patients with post necrotic cirrhosis undergoing liver transplantation were randomized to receive or not ATIII replacement therapy before the induction of anaesthesia and thereafter throughout surgery. Activation of both coagulation and fibrinolysis (increase of thrombin-antithrombin complexes, fibrin and fibrinogen degradation products) were demonstrated in both groups. Blood loss and transfusion requirements were not affected by ATIII administration.


Extracorporeal membrane oxygenation (ECMO) for neonatal respiratory failure.

Extracorporeal membrane oxygenation (ECMO) has been a successful treatment (82% survival) in over 5000 neonates with severe respiratory failure (80% predicted mortality without ECMO). ECMO is prolonged extracorporeal cardiopulmonary bypass achieved by extrathoracic vascular cannulation using a modified heart-lung machine. ECMO is currently the treatment of choice for full-term newborns with severe respiratory failure. The report summarizes indications, resulting complications, and future applications of neonatal ECMO.


Use of the greater omentum for treatment and prophylaxis of anastomotic and stump dehiscence in major airway surgery.

In 6 patients suffering from anastomotic dehiscence following bronchoplastic procedures of the central airways or from acute bronchial stump fistula following pneumonectomy, the therapeutic efficiency of omentopexy in the management of the fistula was investigated. In 5 other patients with an increased risk of anastomotic leakage after sleeve pneumonectomy or pneumonectomy with carinal resection the omentum was effectfully used to prevent such complication. 4 out of 5 evaluable patients had successful treatment of the anastomosis and stump fistula. Complications arising from the additional laparotomy were not observed.


Perioperative antibiotic prophylaxis in general thoracic surgery.

A prospective study of the efficacy of ampicillin in combination with sulbactam, a beta-lactamase inhibitor, (A/S) in perioperative prophylaxis was performed. The study consisted of two independent parts performed at the same time. Part I included 60 patients with lobectomies and segmentectomies. Group A (A/S 1 x 3 g "single shot") was compared with group B (A/S 3 x 3 g). Superficial wound infections occurred in 3 patients of group A and in 2 patients of group B. There was no empyema. Bronchitis and pneumonia were found in 10 patients of group A and in 7 patients of group B. Part II examined 25 pneumonectomies receiving A/S 3 x 3 g for 3 days. Concentrations of ampicillin and sulbactam in serum and lung tissue were determined and showed adequate levels to cope with usual bacteria in lung surgery. There was one superficial wound infection, 2 cases of bronchitis, and 2 cases of pneumonia.


The surgical treatment of spontaneous pneumothorax by video-thoracoscopy.

Since March 1991, 66 patients with spontaneous pneumothorax were treated thoracoscopically employing the principles of minimally invasive surgery. Of these cases, 14 involved a first occurrence, 18 had a pneumothorax longer than 7 days, and 34 were recurrences; causative lung disease was determined in 25 patients. The blebs and bullae were ligated with chromic catgut Roeder loop or resected with the Endo-GIA stapler. If pathological changes to the lung consistent with Vanderschueren's stage IV were found (n = 36), the treatment was extended to include a parietal pleurectomy. No complications requiring therapy were encountered, the average postoperative hospital stay was 3.2 days. During an average observation period of 10 months (1-27) the recurrence rate was 4.5%. Thoracoscopic therapy proved to be a simple and safe method for all forms of spontaneous pneumothorax.


Valvotomy for isolated congenital aortic stenosis in children: prognostic factors for outcome.

Early and late results after surgery for isolated congenital valvar aortic stenosis were evaluated in a total of 86 children under 16 years of age (mean 7.4 years). Primary procedure was always conservative. There were 7/86 (8.1%) early deaths. All infants who died after the operation were younger than 4 months of age. Among the clinical variables tested by the univariate analysis only age and duration of cardiopulmonary bypass were significant prognostic factors for early death. There were 6/67 (7.7%) valve-related late deaths. Multivariate analysis could not identify any risk factors for early and late mortality. Actuarial survival was 97% (95% CL 93-101%) after 5 years, 94% (88-100%) after 10 years, 90% (82-98%) after 15 years, and 87% (77-97%) after 20 years. A total of 22/79 (28%) early survivors had a first reoperation and 5 had a second reoperation. Long follow-up interval was the only significant factor for reoperation. Actuarial reoperation-free interval was 91% (85-98%) after 5 years, 70% (58-81%) after 10 years, and 50% (34-64%) after 15 years. Significant factors for poor valve function were long duration of follow-up, endocarditis, and young age at operation. The probability of normal valve function was 91% (84-98%) after 5 years, 67% (55-79%) after 10 years, and 54% (40-68%) after 15 years.


Effects of pulsatile and nonpulsatile perfusion mode during extracorporeal circulation--a comparative clinical study.

In a prospective randomized study with 80 male patients scheduled for aorto-coronary bypass grafting we investigated the influence of pulsatile and nonpulsatile perfusion mode on cell count (leukocytes, platelets, hematocrit), concentrations of thromboxane (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), plasma hemoglobin, PMN-elastase, complement C3a, clotting factor XII, lactate, plasmatic inhibitors (C1-INH, AT-III, alpha 2-antiplasmin), arterio-venous oxygen difference (AVDO2) and hemodynamic parameters. Changes in hematocrit were similar in both groups, whereas plasma hemoglobin concentration was significantly higher with pulsatile perfusion. Platelet count paralleled changes in hematocrit and was not influenced by the perfusion mode. Leukocyte count as well as concentrations of PMN-elastase and C3a showed a strong increase during cardiopulmonary bypass, but there were no significant differences between the two groups. Similar changes of the concentrations of TXB2 and 6-keto-PGF1 alpha were noted irrespective of the perfusion mode applied. The observed alterations in the concentrations of clotting factor XII, alpha 2-antiplasmin, AT-III and C1-INH largely paralleled hematocrit changes in either flow mode. Significant differences between the two groups were found with lactate: with nonpulsatile perfusion there was a slight but continuous increase, while with pulsatile flow lactate levels remained unchanged. There was no evidence for a better oxygen uptake (AVDO2) with pulsatile perfusion. Pulsatile perfusion seems to be advantageous to tissue perfusion, however, at the cost of a higher rate of hemolysis. We cannot confirm further salutary effects of the pulsatile perfusion mode with the 1-pump-system on cellular and humoral blood constituents.(ABSTRACT TRUNCATED AT 250 WORDS)


Experimental and first clinical experiences with implantable ultrasonic Doppler probes for postoperative bypass control after coronary surgery.

Concerning postoperative bypass hemodynamics after open heart surgery only few data are known. With this new implantable doppler probe we developed an easy-to-use bedside method for monitoring postoperative bypass function after coronary artery bypass grafting. The accuracy of our method is shown by using a circulation model and by animal studies. Furthermore first clinical data are shown which support our conclusion of having found a sensitive method for monitoring small vessels' hemodynamics.


The use of mesh-tube-constricted dilated or varicose veins as arterial bypass conduit.

In general, dilated and varicose veins are not used as arterial bypass grafts despite their physiological endothelial lining. A uniform small diameter may be achieved by inserting such veins into mesh tubes. To test the degree to which dilated veins can be constricted without forming folds, in-vitro and experimental investigations were performed before such composites were used for clinical reconstructive surgery. Ovine jugular veins with a diameter of 15 mm were inserted into 6 mm tubes. After casting in paraffin wax none of the specimens showed folds on the flow surface. In 12 sheep pairs of mesh-constricted jugular veins and native femoral veins were implanted as femoropopliteal bypass grafts. Six animals were killed at 6 months and 6 at one year. All bypasses remained patent and none showed signs of obstruction caused by folds or anastomotic hyperplasia at angiographic control. Intimal hyperplasia was significantly reduced from 416 +/- 143 microns in the midportion of native vein grafts to 231 +/- 76 microns (p = 0.0001 paired t-test) in constricted veins as well as at the anastomoses (358 +/- 256 microns vs. 180 +/- 73 microns; p = 0.008). Partially or totally mesh-tube-constricted varicose veins were used for infrainguinal reconstructions in 19 patients and for coronary revascularization in 3. All grafts showed an even calibration at control angiography. As constriction does not lead to internal folds, varicose or dilated veins may be used successfully as bypass grafts after insertion into mesh tubes. The external reinforcement reduces the intimal hyperplasia within the graft and also reduces anastomotic hyperplasia.


Aortic valve replacement with the pulmonary autograft--experience of 23 cases.

Since 1988 an intensive homograft-program has existed at the Linz General Hospital. We have installed an own hospital-based homograft bank, where the allografts, after a 24-hour sterilization-period in an antibiotic solution and a controlled freezing procedure, are stored in liquid nitrogen at -196 degrees C. In 1991 for the first time aortic valve replacement was performed by pulmonary autograft in 23, mainly younger, patients. Essentially our technique conforms with that of D. N. Ross, in the course of which 18 autografts were implanted in subcoronary position and 5 aortic-root replacements were performed. 3 patients died perioperatively, 2 times a severe post-operative bleeding with following hypoxemic brain damage being the cause; 3 more patients had to be rethoracotomized because of postoperative bleedings. All these were attributed to a technical difficulty, which was overcome. In one patient a left-ventricular assist device had to be installed due to a left-ventricular failure, a successful heart transplantation followed on the 8th postoperative day. A follow-up was conducted in all patients every 3 months. In 2 patients a substantial valve incompetence of grade II-III and grade III was detected, all other patients showed no regurgitation of clinical relevance. Despite our initial difficulties it is our opinion that the many advantages-no anticoagulation necessary, no valve sound, less incidence of bacterial endocarditis, and longer durability-do justify this operative procedure.


Isolated coronary artery bypass grafting in patients 75 years of age and older: is age per se a contraindication?

137 patients with a mean age of 77.3 years (Group A) who underwent isolated coronary artery bypass grafting (CABG) were compared to 137 patients with a mean age of 55.6 years (Group B) who also underwent isolated CABG on the same or the adjacent day as the Group A patients. Group A patients were more commonly women, and had a significantly higher incidence of unstable angina, emergency operations, extensive coronary disease, peripheral vascular disease, and multiorgan debility. However, their left-ventricular function and the extent of revascularisation was similar to Group B patients. They also had significantly more operative mortality (7.2% vs 1.45%, p < 0.001). cardiac and non-cardiac complications, and longer hospital stay (14.2 vs 8.8 days, p < 0.001) than group B patients. At a mean follow-up of 29.8 months, no significant differences were noted in Group A versus Group B patients in terms of long-term survival (95% vs 94%), freedom from angina (82% vs 81%), cardiac readmission (10% vs 12%), or in the incidence of new myocardial infarction or new CABG. Actuarial survival at 4 years was 76.9% in Group A patients and 90.1% in Group B patients. Severe angina due to extensive coronary disease commonly makes urgent surgery unavoidable in this growing population of very old patients, but the operative mortality is modest and survivors do enjoy several years of life, remaining as free of angina, etc., as similar but younger patients.


Low-output syndrome after heart surgery: is a monotherapy with phosphodiesterase-III inhibitors feasible? A comparative study of amrinone and enoximone.

In order to determine whether the primary use of a phosphodiesterase-III (PDE) inhibitor as monotherapy for severe cardiac low-output states (LOS) is in fact practicable, we investigated the haemodynamic effects of amrinone and enoximone in a prospective randomized study. After elective CABG, AVR, or MVR, patients with cardiac LOS were given amrinone (n = 10) or enoximone (n = 9). Following bolus saturation (1.0-2.0 mg/kg [XA = 1.4] or 0.5-1 mg/kg [XE = 0.9] in total), a dose of 5-10 microgram/kg/min was given by infusion. The standard monitoring program included discontinuous haemodynamic measurements (Swan-Ganz) over a maximum time period of 48 hours, arterial and venous blood-gas analyses, and clinical chemistry. The preoperative clinical and haemodynamic status of the enoximone (E) group (55% CABG patients; MPAP 27 +/- 2.5 mmHg, PCWP 20 +/- 2.9 mmHg, PVR 201 +/- 35 dyn.s.cm-5) was considerably worse than that of the amrinone (A) group (70% CABG patients; MPAP 23 +/- 2.3 mmHg, PCWP 16 +/- 3.5 mmHg, PVR 153 +/- 28 dyn.s.cm-5). Both PDE inhibitor preparations led to a significant increase in cardiac index (from 1.9 +/- 0.1 to 2.5 +/- 0.12 L/min/m2 (A) and from 1.98 +/- 0.1 to 2.6 +/- 0.18 L/min/m2 (E) within 30 minutes, accompanied by a simultaneous decrease in filling pressures and vascular resistances. For up to 2 hours, 3/10 (A) and 2/9 (E) patients required additional positive inotropic support with adrenaline. There were no significant differences between the two groups at any time.(ABSTRACT TRUNCATED AT 250 WORDS)


Congenital intrapericardial aneurysm of the left-atrial appendage.

An interesting case of congenital intrapericardial aneurysm of the left-atrial appendage is reported. The patient presented with recurrent supraventricular arrhythmias and progressive exercise intolerance and fatigue. Computerised axial tomography aided in the diagnosis by excluding the presence of any thrombus in the sac. The aneurysm could be safely excised via a left thoracotomy without cardiopulmonary bypass. The relevant literature on this problem is briefly discussed.


[Design of a tibial intramedullary nail based on anatomic studies of intraosseous vessels].

The design of the tibial medullary nail can be improved in order to preserve intraosseus vessels by osteosynthesis of the tibia. The nutrient artery of the human tibia enters the compacta in an average height of 33% dorsally and is leaving it in a height of 50% of the tibial length. In the medullary cavity the vessel splits up. The main branch continues the distal course on the dorsal/dorsolateral side of the medullary cavity (endosteal). In the distal diaphysis this endosteal vessel is of great importance, since the periosteal blood supply in this region with high incidence of pseudarthrosis is guaranteed only by branches of the anterior tibial artery. Using a new unreamed tibial nail, which is flattened dorsally, it is possible to preserve the endostal main artery of the tibia.


[Morphometric analysis of the vascular tree of fetal tubular bones in an experimental model].

The area of interest for the longitudinal growth is the distal growth plate. In a postmortem study we were interested in changes of the epiphyseal vascular length density after fracture and surgical therapy of foetal and neonatal femora (25th to 40th post conceptional weeks). We formed three groups of equal size. Group A (25 femora) was the control group. In group B and C we performed fractures in the middle third of the femora, in group C the femora was operated with a plate afterwards. A microangiography of all femora occurred and after plastination transparent slices were produced. In this manner we could study the epiphyseal vessels in the growth plate. Using image analyses we could show that vascular density of the epiphyseal growth plate could be verified only through fracture but not by surgical therapy. The integrity of the distal epiphyseal vascular architecture is the aim after all.


[Evaluating the independence of paraplegic patients at the end of the first rehabilitation--a multicenter project of computer-assisted quality control in rehabilitation].

Rehabilitation of patients who became handicapped due to illness or trauma is a difficult process, involving many therapeutic sections. The necessity to document the results of different rehabilitation programs led to the development of numerous scoring systems in the USA within the last 25 years, considering mainly functional results. The present functional assessment score (DMGP-Selbständigkeitserfassung für Tetraplegiker) for the documentation of self-sufficiency in tetraplegic patients after primary rehabilitation has been designed to record the quality of rehabilitation programs and has been exclusively designed for patients with quadriplegia, it there fore has the advantage of a better and more precise documentation over other general functional scoring systems, especially for the interests of different sections (occupational therapy, physiotherapy) being involved in this special rehabilitation program. The aim of the documentation is to record the degree of independence of tetraplegic patients after primary rehabilitation, considering the individual requirements of aids and the assumption of circumstances suitable for wheel-chairs. Since all data are collected on a computer-readable form each participating clinic has the opportunity for an individual analysis of the own results, as well as the opportunity of comparing it with the collective results.


[Complications after surgical management of radial head fractures].

As surgical management of fractures of the head of the radius unfortunately does not always yield satisfactory results, we performed a detailed study of these complications with special regard to several criteria. Over a period of five years, 44 cases of fractures of the head of the radius received surgical treatment at the Graz Hospital for Accident Surgery. Correlating with the literature known to us we found a relatively high rate of complications (17 of 44 cases, nine of the 17 cases required reoperation). If, however, we consider cases with a loss of mobility of up to 30 degrees in bending and stretching and rotation of the forearm still as satisfactory, of our 44 patients who were operated on for fractures of the head of the radius 37 showed satisfactory results and only seven poor ones.


[Treatment of closed dislocations of the knee joint].

Nineteen knee dislocations in 18 patients (one bilateral) occurred over a period of twelve years. The age range was 17 to 70 years with an average age of 33 years. There was no injury of the popliteal artery and five peroneal nerve injuries in the group. One compartment syndrome occurred after reduction. The follow-up study including examination showed good and satisfactory results for early surgical repair. After delayed surgical repair there were more signs of instability, pain and restrictive range of flexion movement. Early operative repair followed by cast bracing for six weeks and an intensive mobilisation therapy after cast bracing are the method of choice. An immobilisation period of three to four weeks is possible.