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Biomedical subjects

J Weil

Publications and source records attributed to J Weil.

At least 55 records · Page 3Linked to original sources
PubMed1998

Percutaneous closure of secundum atrial septal defect with a new self centering device ("angel wings").

OBJECTIVE: To investigate the safety, efficacy, and clinical application of a new self centering device ("angel wings") for closure of secundum atrial septal defects (ASD II) and persistent foramen ovale in all age groups. DESIGN: Multicentre, prospective, nonrandomised study. PATIENTS INCLUSION CRITERIA: defects with an occlusive diameter of < or = 20 mm and a surrounding rim of > 4 mm; body weight > 10 kg; and an indication for surgical closure of secundum atrial septal defect. Additionally, there were compassionate indications for closure in patients with persistent foramen ovale. INTERVENTIONS: Defects were closed by a transcatheter device consisting of two square frames made of superelastic nitinol wire. The frames are covered by elastic polyester fabric, which is sewn together at a central circle. All procedures, except for three interventions that were carried out under sedation, were performed under general anaesthesia using transoesophageal echocardiography and fluoroscopy to monitor intervention. RESULTS: Closure was attempted in 75 (71%) of 105 patients. An ASD II was present in 35 children and 15 adults. A persistent foramen ovale was present in 25 adults with suspected paradoxical embolism. Transcatheter closure was unsuccessful in three children and crossover to surgery was required. Residual shunts were found in 20 patients (27%) immediately after the procedure. A transient atrioventricular third degree block occurred in three patients (4%) and the right atrial disk was not fully deployed in three. A minor shunt (< 3 mm) was present in only three (4%) of 72 patients during follow up of 1-17 months. Blood clots on the right atrial disks in two patients (one required lysis) were seen during follow up transoesophageal echocardiography. Serious complications demanding surgical removal of the device occurred in three patients. One patient had haemopericardial tamponade because of an aortic lesion. Left atrial thrombus formation due to an unfolded right atrial disk was found in a second patient and dislodgement of the left atrial disk resulted in a large residual shunt in a third. CONCLUSIONS: Percutaneous closure of a central ASD with a diameter < or = 20 mm in paediatric and adult patients is feasible and effective with this new device. It is a promising alternative to surgical closure. Modifications of the design, however, seem to be mandatory as 4% of patients developed serious complications.

Adolescent↗
PubMed1998

Localization of preproenkephalin mRNA in rat heart: selective gene expression in left ventricular myocardium.

The enkephalins are derived from a common precursor protein known as preproenkephalin (ppENK). Enkephalins appear to be one of the endogenous ligands for the opiate receptors. In the rat the ventricular myocardium contains more ppENK mRNA than any other tissue. To gain further insight into the role of cardiac enkephalins, the regional and developmental distribution of ppENK mRNA was studied by Northern blotting and in situ hybridization. In the early postnatal period, ppENK mRNA is low in atrial and ventricular myocardium. With maturation, ppENK expression increases threefold in left and right ventricular tissue, but not in the atria or cardiac conductive system. Interestingly, ppENK mRNA levels are four times higher in the left than in the right chamber. Thus, to our knowledge, ppENK is the only gene exhibiting marked differences in expression between the adult right and left ventricle. Given the left-side preference of ppENK expression, the possibility is raised that the left ventricle is an endocrine organ that supplies the body with enkephalins.

Aging↗
PubMed1997

Reduction of myocardial myoglobin in bovine dilated cardiomyopathy.

Myoglobin levels are decreased in various animal models of heart failure, a change that has been associated with compromised energy supply. The underlying mechanisms by which myoglobin content decreases in failing myocardium are unknown. Bovine hereditary cardiomyopathy (bCMP) displays several characteristics of human dilated cardiomyopathy with a marked desensitization of the beta-adrenoceptor signal cascade. The aim of the present study was to investigate whether a similar reduction of myoglobin can be seen in this animal model, and to elucidate the possible mechanism of this reduction. Myoglobin protein concentration was decreased by 46-47% (P < 0.05) in left and right ventricular myocardium of failing hearts (n = 9) compared to control hearts (n = 11). No difference was found between atria of diseased and control animals. Immunohistochemistry with a polyclonal antibody against myoglobin revealed a strong and uniform labeling in cardiomyocytes of non-failing hearts. Using microscopic densitometry, immunosignals were significantly decreased in ventricular myocytes of bCMP hearts (168 +/- 5.3 v 118 +/- 8.6 arbitrary units, P < 0.05). Moreover, myoglobin was heterogeneously distributed in bCMP hearts, with single myocytes showing no staining. Slot blot analysis of total RNA demonstrated a 40-50% reduction (P < 0.05) of myoglobin mRNA levels in ventricular but not in atrial myocardium of bCMP hearts. The results support the view that a decrease of myocardial myoglobin is a general phenomenon in end-stage heart failure. It appears to be primarily due to reduced gene expression but may be aggravated by leaking from single myocytes. The decrease of myoglobin may contribute to the imbalance between energy production and energy expenditure in heart failure.

Animals↗
PubMed1997

The dorsal middle phalangeal finger flap. Mid-term results of 43 cases.

The dorsal middle phalangeal finger (DMF) flap is a (neuro)vascular island flap based on one palmar proper digital artery, its venae comitantes (and/or a separate dorsal vein) and the dorsal branch(es) of the palmar digital nerve. The main nerve supply of the donor finger is left undisturbed. The flap may be raised on a short antegrade, long antegrade or a retrograde pedicle, and used as a free, arterial and/or venous flow-through or neurovascular flap. In a prospective study (mean follow-up of 50 months), the results of 43 DMF flaps were analysed. All flaps survived, retained patency of their vascular pedicles and fulfilled their goals. Neurovascular flaps provided sensate coverage at the S3+ level with static 2-point discrimination values of about 10 mm. Dissection between the proper digital nerve and the rest of the neurovascular bundle induced a 5% incidence of cold intolerance and a 12% occurrence of S3+ hypaesthesia. Advantages, drawbacks and indications of DMF flaps are outlined.

Adolescent↗
PubMed1997

Three-dimensional reconstitution of embryonic cardiomyocytes in a collagen matrix: a new heart muscle model system.

A method has been developed for culturing cardiac myocytes in a collagen matrix to produce a coherently contracting 3-dimensional model heart tissue that allows direct measurement of isometric contractile force. Embryonic chick cardiomyocytes were mixed with collagen solution and allowed to gel between two Velcro-coated glass tubes. During culture, the cardiomyocytes formed spontaneously beating cardiac myocyte-populated matrices (CMPMs) anchored at opposite ends to the Velcro-covered tubes through which they could be attached to a force measuring system. Immunohistochemistry and electron microscopy revealed a highly organized tissue-like structure of alpha-actin and alpha-tropomyosin-positive cardiac myocytes exhibiting typical cross-striation, sarcomeric myofilaments, intercalated discs, desmosomes, and tight junctions. Force measurements of paced or unpaced CMPMs were performed in organ baths after 6-11 days of cultivation and were stable for up to 24 h. Force increased with frequency between 0.8 and 2.0 Hz (positive "staircase"), increasing rest length (Starling mechanism), and increasing extracellular calcium. The utility of this system as a test bed for genetic manipulation was demonstrated by infecting the CMPMs with a recombinant beta-galactosidase-carrying adenovirus. Transduction efficiency increased from about 5% (MOI 0.1) to about 50% (MOI 100). CMPMs display more physiological characteristics of intact heart tissue than monolayer cultures. This approach, simpler and faster than generation of transgenic animals, should allow functional consequences of genetic or pharmacological manipulation of cardiomyocytes in vitro to be studied under highly controlled conditions.

Actins↗
PubMed1996

Enzyme conversion of lignocellulosic plant materials for resource recovery in a Controlled Ecological Life Support System.

A large amount of inedible plant material composed primarily of the carbohydrate materials cellulose, hemicellulose, and lignin is generated as a result of plant growth in a Controlled Ecological Life-Support System (CELSS). Cellulose is a linear homopolymer of glucose, which when properly processed will yield glucose, a valuable sugar because it can be added directly to human diets. Hemicellulose is a heteropolymer of hexoses and pentoses that can be treated to give a sugar mixture that is potentially a valuable fermentable carbon source. Such fermentations yield desirable supplements to the edible products from hydroponically-grown plants such as rapeseed, soybean, cowpea, or rice. Lignin is a three-dimensionally branched aromatic polymer, composed of phenyl propane units, which is susceptible to bioconversion through the growth of the white rot fungus, Pluerotus ostreatus. Processing conditions, that include both a hot water pretreatment and fungal growth and that lead to the facile conversion of plant polysaccharides to glucose, are presented.

Biodegradation, Environmental↗
PubMed1996

Regulation of the human Gi alpha-2 gene promotor activity in embryonic chicken cardiomyocytes.

Increased expression of the inhibitory G protein Gi alpha-2 is assumed to contribute to desensitization of adenylyl cyclase in human heart failure. The mechanisms of upregulation involve increases in myocardial Gi alpha-2 protein, mRNA and gene transcriptional activity. To elucidate these mechanisms in more detail, the 5' flanking region of the human Gi alpha-2 gene (-1214/+115 bp) was cloned upstream of the bacterial chloramphenicol acetyltransferase (CAT) gene and transfected in embryonic chick cardiomyocytes. CAT activity was measured 48 h after transfection. Unstimulated activity of the -1214/+115 bp construct was about 10-fold higher than activity of the basal CAT-construct (pGEMCAT). 5' deletion from -1214/+115 to -85/+115 bp upstream of the transcriptional start site increased, further stepwise deletions to 46/+115 gradually decreased promotor activity. Deletion from -46/+115 to -33/+115 bp completely abolished promotor activity. Stimulation of cardiomyocytes that had been transfected with the -1214/+115 CAT-construct with isoprenaline (10 microM), forskolin (10 microM), forskolin (10 microM) plus IBMX (10 microM) or dibutyryl-cAMP (1 mM) for 24 h induced an increase in CAT activity to 139 +/- 12% (n = 9), 211 +/- 18% (n = 12), 256 +/- 20% (n = 5) and 198 +/- 28% (n = 7) of unstimulated values, respectively. We conclude: 1) In chicken cardiomyocytes a sequence element of 52 bp between -85 and -33 bp is necessary to provide basal Gi alpha-2 promotor activity. 2) Elevation of cAMP has a stimulatory effect on the human Gi alpha-2 promotor, thereby offering a mechanism for beta-adrenoceptor-mediated increases in Gi alpha-2 in the heart.

Animals↗
PubMed1995

Prophylactic aspirin and risk of peptic ulcer bleeding.

OBJECTIVE: To determine the risks of hospitalisation for bleeding peptic ulcer with the current prophylactic aspirin regimens of 300 mg daily or less. DESIGN: A case-control study with hospital and community controls. SETTING: Hospitals in Glasgow, Newcastle, Nottingham, Oxford, and Portsmouth. SUBJECTS: 1121 patients with gastric or duodenal ulcer bleeding matched with hospital and community controls. RESULTS: 144 (12.8%) cases had been regular users of aspirin (taken at least five days a week for at least the previous month) compared with 101 (9.0%) hospital and 77 (7.8%) community controls. Odds ratios were raised for all doses of aspirin taken, whether compared with hospital or community controls (compared with combined controls: 75 mg, 2.3 (95% confidence interval 1.2 to 4.4); 150 mg, 3.2 (1.7 to 6.5); 300 mg, 3.9 (2.5 to 6.3)). Results were not explained by confounding influences of age, sex, prior ulcer history or dyspepsia, or concurrent non-aspirin non-steroidal anti-inflammatory drug use. Risks seemed particularly high in patients who took non-aspirin non-steroidal anti-inflammatory drugs concurrently. CONCLUSION: No conventionally used prophylactic aspirin regimen seems free of the risk of peptic ulcer complications.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

The ryanodine binding sarcoplasmic reticulum calcium release channel in nonfailing and in failing human myocardium.

The ryanodine-sensitive Ca2+ release channel (RyaCRC) of the sarcoplasmic reticulum plays a key role in the intracellular Ca2+ handling in cardiomyocytes. Altered expression of the RyaCRC has been supposed to contribute to abnormal cellular Ca2+ handling and to myocardial dysfunction in dilated and ischemic cardiomyopathy. In the present study the 3H-ryanodine binding site in human myocardial homogenates was characterized and the density of the RyaCRC (which corresponds to the cardiac ryanodine receptor) was determined in nonfailing and in failing human myocardium. Homogenates were prepared from nonfailing left ventricular myocardium from the hearts of 5 organ donors (NF) and from failing myocardium from 14 explanted hearts of transplant recipients with end-stage heart failure resulting from dilated (DCM, n = 5) or ischemic (ICM, n = 9) cardiomyopathy. Radioligand saturation binding experiments revealed a specific, high-affinity 3H-ryanodine binding site (Kd-values: NF: 0.65 +/- 0.11 nmol/l, DCM: 0.66 +/- 0.09 nmol/l, ICM: 0.88 +/- 0.18 nmol/l; n.s.) in all preparations. Specific 3H-ryanodine binding depended on the free Ca2+ concentration in the assay. It was maximal at 3-100 micro mol/l Ca2+. The binding was inhibited by the RyaCRC antagonists ruthenium red (Ki-value: 0.32 [0.18-0.56] micromol/l, n = 5) and Mg2+ (Ki-value: 2.95 [1.23-7.11] mmol/l, n = 5). The RyaCRC density was 103.5 +/- 11.9 fmol/mg protein in nonfailing myocardium. There was no significant change in the RyaCRC density in dilated or ischemic cardiomyopathy (112.4 +/- 17.1 and 122.7 +/- 13.9 fmol/mg protein) compared to nonfailing control myocardium. In summary, 3H-ryanodine binds specifically and with high-affinity to the RyaCRC in human myocardium. There is no change in the RyaCRC density in failing myocardium of patients with DCM or ICM in comparison to non-failing controls.

Adult↗
PubMed1995

Bovine hereditary cardiomyopathy: an animal model of human dilated cardiomyopathy.

UNLABELLED: Bovine hereditary cardiomyopathy (bCMP) displays clinical characteristics of human idiopathic dilated cardiomyopathy (DCM). We studied isometric force of contraction in right ventricular trabeculae, plasma and tissue catecholamines, beta- and alpha 1-adrenoceptor density, Gi proteins and adenylyl cyclase activity in eight hearts with bCMP and eight control hearts (right and left atria and ventricles each). RESULTS: Compared to control, the potency of isoprenaline in bCMP was eight-fold decreased, whereas the maximal positive inotropic effect of isoprenaline as well as the efficacy and potency of calcium were unchanged. Plasma noradrenaline was increased by 240%. Tissue noradrenaline and adrenaline were decreased by 36-63% and 58-69%, whereas dopamine was increased by 105-218%. beta-adrenoceptor density was drastically reduced by 90%, but binding affinity was unchanged. alpha-Adrenoceptor density and binding affinity were unchanged. Total PTX-substrates were increased in bCMP by 28-99%. Basal adenylyl cyclase activity was decreased by 36-47%. Similarly, stimulation by GTP, GMPPNP, isoprenaline, sodium fluoride, manganese or forskolin was attenuated by 26-62% (atria) and 45-66% (ventricles). In conclusion, we found marked activation of the sympatho-adrenergic system, downregulation of beta-adrenoceptors, upregulation of Gi proteins, global desensitization of adenylyl cyclase and selective subsensitivity to beta-adrenergic inotropic stimulation. These results closely resemble the characteristic alterations in the beta-adrenoceptor-G protein-adenylyl cyclase pathway in human heart failure, indicating that they are general features of heart failure. The similarity to human DCM, the inheritance and the availability of large tissue samples make bCMP a suitable model for human DCM.

Adenylate Cyclase Toxin↗
PubMed1995

Enrichment of G protein alpha-subunit mRNAS in the AV-conducting system of the mammalian heart.

We investigated the expression pattern of the heterotrimeric G proteins Gs alpha, Gi alpha-2 and Go alpha in rat and guinea-pig heart by in situ hybridization. Cryosections were hybridized with single-stranded 35S-cRNA probes complementary to subtype-specific sequences of the respective mRNAs. Hybridization signals were visualized by exposition to X-ray films and dipping autoradiography. The rank order of abundance was Gi alpha-2 approximately Gs alpha >> Go alpha. In general, G protein alpha-subunit mRNAs were evenly distributed in the heart including endo- and epicardium, large vessels and valves. Go alpha-mRNA levels were significantly higher in atria than in ventricles. In contrast to the rather uniform labeling of working myocardium, expression of all three G proteins was enriched in small intramural blood vessels and in subendocardial Purkinje fibers of septum and papillary muscles. A more marked enrichment of Gs alpha-, Gi alpha-2- and especially Go alpha-mRNA was seen in neuronal ganglionic cells in the atrial septum and posterior regions of the atrium. The main finding, however, was an enrichment of all three G protein mRNAs in the atrioventricular conductive tissue. The accumulation was strictly co-localized with acetylcholinesterase-positive regions identified as the atrioventricular node, the bundle of His and the right and left bundle branches and was seen similarly in rat and guinea-pig hearts. Quantitative in situ hybridization revealed Gs alpha-, Gi alpha-2- and Go alpha-mRNA levels in the bundle of His to be 206 +/- 0.13%. 191 +/- 0.15% and 165 +/- 0.06%, respectively, of that in the surrounding interventricular working myocardium. These findings indicate that heterotrimeric G proteins play an important role in modulation of electrical conductance in the heart.

Acetylcholinesterase↗
PubMed1995

Predictors of early deterioration and mortality in black Americans with spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Black Americans with spontaneous intracerebral hemorrhage (SICH) may have unique clinical characteristics that affect outcome. The aim of this study was to determine the prognostic value of clinical characteristics and initial CT scan for outcome in black Americans with SICH. METHODS: Clinical and demographic data were extracted from the charts of 182 consecutive black Americans admitted for SICH diagnosed by clinical criteria and initial CT scan. Hemorrhage volumes were calculated from admission CT scans by a computerized method. Univariate and multiple logistic regression analyses were performed to determine independent predictors of early deterioration (defined as a decrease from an initial Glasgow Coma Scale score > 12 by > or = 4 points within 24 hours from presentation) and mortality. RESULTS: Both hemorrhage volume and ventricular extension were significant, independent predictors of early deterioration (odds ratio [OR], 6.78; 95% confidence interval [CI], 1.89 to 24.35 and OR, 4.67; 95% CI, 1.30 to 16.72, respectively) and mortality (OR, 6.66; 95% CI, 2.85 to 15.58 and OR, 4.23; 95% CI, 1.82 to 9.82, respectively). A Glasgow Coma Scale score < or = 12 also predicted mortality (OR, 3.23; 95% CI, 1.46 to 7.14). Initial mean arterial pressure was not an independent predictor of early deterioration or mortality. CONCLUSIONS: Hemorrhage volume and ventricular extension are the best predictors of early deterioration and mortality in black Americans with SICH.

Black People↗
PubMed1994

Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs.

Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of peptic ulcer complications, but it is not clear whether some drugs are more likely than others to cause such complications. We compared previous use of NSAIDs in 1144 patients aged 60 and older admitted to hospitals in five large cities with peptic ulcer bleeding and in 1126 hospital controls and 989 community controls matched for age and sex. Peptic ulcer bleeding was strongly associated with use of non-aspirin NSAIDs of any type during the 3 months before admission (411 cases, 351 controls; odds ratio 4.5 [95% CI 3.6 to 5.6]). The odds ratios for peptic ulcer bleeding were lowest for ibuprofen (2.0 [1.4-2.8]) and diclofenac (4.2 [2.6-6.8]), and intermediate for indomethacin, naproxen, and piroxicam (11.3 [6.3-20.3], 9.1 [5.5-15.1], and 13.7 [7.1-26.3]). Azapropazone and ketoprofen carried the highest risks (31.5 [10.3-96.9] and 23.7 [7.6-74.2]). Risks also increased with drug dose (low dose 2.5 [1.7-3.8], intermediate 4.5 [3.3-6.0], and high 8.6 [5.8-12.6]) for all drugs combined. Appropriate clinical strategies could prevent many episodes of peptic ulcer bleeding: NSAIDs should be used only in patients who do not respond to other analgesics; the lowest possible doses should be used; and the least toxic NSAIDs should be selected.

Aged↗
PubMed1994

Cellulose pretreatments of lignocellulosic substrates.

Cellulose in inedible plant materials, forestry residues, and municipal wastes must be pretreated to disrupt its physical structure, thereby making its hydrolysis to glucose practical. Developments since 1991 are summarized.

Acids↗
PubMed1994

Self expanding stents in congenital heart disease.

OBJECTIVES: To show potential indications for and clinical use of self expanding stents in patients with congenital heart disease. DESIGN: Descriptive study of selected, non-randomised patients with balloon expandable but persistent stenoses in whom the use of a balloon expandable stent was considered suboptimal or impossible. SETTING: A tertiary referral centre. PATIENTS: 10 patients, aged 15 days to 32 years. Six patients after atriopulmonary or cavopulmonary anastomosis, two with pulmonary atresia and multiple aortopulmonary collaterals, one with coarctation of the aorta, and one with congenital pulmonary venous stenosis. RESULTS: Successful, uncomplicated, placement of 10 stents with the desired haemodynamic results, even in tortuous vessels with many stenoses. CONCLUSIONS: Self expanding stents have a role in the treatment of patients with congenital heart disease. They should be considered when a smaller delivery system and flexibility would aid placement, or in the treatment of long or multiple sequential stenoses.

Adolescent↗