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PubMed1980

The sulphatase of ox liver. XXIII. The nature of substrate-modified sulphatase A.

An improved method is described for the preparation of milligram quantities of substrate-modified sulphatase A. The latter has the same molecular weight and the same ability to form a tetramer as has native sulphatase A. It has been shown that the modified enzyme prepared with nitrocatechol [35S]sulphate as substrate contains 1 mol 35SO24- per mol enzyme and that any treatment which causes reversion of the modified enzyme to native enzyme is accompanied by the loss of the bound SO24-. Dialysis of the 35S-modified enzyme against a solution containing SO24- causes a loss of 35SO24- with no change in the amount of modified enzyme in the preparation. It has been shown that the activation of the substrate-modified enzyme by SO24- does not lead to the formation of a third stable form of sulphatase A.

Animals↗
PubMed1977

Preparation and enzymatic hydrolysis of dinucleoside monophosphates and DNA modified with aromatic residues.

The following procedures have been used to prepare fifteen modified dinucleoside monophosphates: (a) bisulfite-catalyzed transamination with aniline to give an N4-phenylcytidine (CPh), (b) bisulfite-catalyzed transamination with beta-naphthylamine to give an N4-beta-naphthylcytidine (CbetaN), (c) alkylation with 7-bromomethylbenz[a] anthracene to afford a 7(benz[a]anthryl-7-methyl)guanosine (GMBA), and (d) reaction with N-acetoxy-2-acetylaminofluorene to give an 8-(N-2-fluorenylacetamido)guanosine (GAAF). The compounds prepared were A-CPh, CPh-A, CPh-G, U-CPh, CPh-U, A-CbetaN, CbetaN-A, G-CbetaN, CbetaN-G, U-CbetaN, CbetaN-U, GMBA-U, U-GMBA, GAAF-U, and U-GAAF. All of the modified compounds were hydrolyzed to the expected monomers with venom and spleen exonucleases. Hydrolysis by micrococcal nuclease was inhibited in the following cases: A-CPh, A-CbetaN, U-GMBA, and U-GAAF. The first three reactions above were applied to denatured calf thymus DNA to prepare modified DNA samples containing from 0.3 to 2.0% bound aromatic residues. The modified nucleic acids were completely hydrolyzed to nucleosides by the combination of venom exonuclease, deoxyribonuclease I and alkaline phosphatase. The same results were obtained with a combination of spleen exonuclease, deoxyribonuclease II, and alkaline phosphatase. Hydrolysis of the modified nucleic acids by micrococcal nuclease and alkaline phosphatase afforded primarily nucleosides, with some dinucleoside monophosphates. The amount of the latter did not exceed that found in the hydrolysis of control DNA, however. Other workers have observed inhibition of enzymatic hydrolysis of nucleic acids modified by aromatic carcinogens. We postulated that their results may have been caused by cross-links, which were avoided in our studies.

Animals↗
PubMed1991

Survival and differentiation within the adult mouse striatum of grafted rat pheochromocytoma cells (PC12) genetically modified to express recombinant beta-NGF.

Rat pheochromocytoma PC12 cells were genetically modified in vitro to express recombinant beta-nerve growth factor (beta-NGF) using a replication-deficient retroviral vector carrying the mouse beta-NGF gene and subsequently implanted into the striatum of a mouse model of Parkinson's disease. The fate of the genetically modified PC12 cells (PC12N.8) was assessed at varying times postimplantation by studying immunoreactivity (IR) to tyrosine hydroxylase (TH) or the rat NGF receptor (NGFR). In vitro, the genetically modified PC12 cells displayed a neuronal morphology in the absence of exogenous NGF which was characterized by extensive neurite outgrowth. In addition, the genetically modified PC12 displayed a catecholaminergic phenotype in vitro as assessed by TH-IR. Following implantation into the striatum, the survival of PC12N.8 cells was limited. Surviving cells could be identified by NGFR-IR, but not by TH-IR. In addition, PC12N.8 cells with a neuronal morphology similar to that observed in vitro were only rarely observed in vivo. No tumors were observed in PC12N.8 graft recipients up to 30 days postimplantation. In contrast, intrastriatal tumors were observed in 50% of the PC12 cell recipients. These data demonstrate that PC12 cells genetically modified in vitro to synthesize beta-NGF do not revert to the mitotic phenotype of the parent PC12 cell line following implantation into the adult striatum, an observation that suggests that these cells may continue to express recombinant beta-NGF in vivo. The data further suggest that the genetically modified PC12 cells lose the catecholaminergic phenotype following implantation into the striatal parenchyma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1988

Quantification of plasma lipids and apolipoproteins in British Halflop rabbits. A comparison between normocholesterolemic rabbits, hypercholesterolemic rabbits (modified WHHL rabbits) and rabbits fed an atherogenic diet.

We have established isolation methods and developed electroimmunoassays for rabbit apolipoprotein A-I (apo A-I), apo B, apo C-III and apo E. The assays were used to characterize a hyperlipidemic strain of the British Halflop rabbits (BHL rabbits), obtained after cross-breeding with WHHL rabbits and referred to as modified WHHL rabbits, and to investigate the changes in the apolipoprotein levels induced by feeding normal BHL rabbits an atherogenic diet (0.25% cholesterol and 3% coconut oil). The modified WHHL rabbits were characterized by increased levels of apo B, apo C-III and apo E as well as cholesterol, phospholipids and triacylglycerol as compared to chow-fed BHL rabbits, while the apo A-I levels were only half of those found in the chow-fed animals. The modified WHHL rabbits had virtually no low density lipoprotein (LDL) receptor activity and a low fractional catabolic rate (FCR) of LDL. These results indicate that the modified WHHL rabbit has the homozygous form of the LDL receptor deficiency. The BHL rabbits fed the atherogenic diet showed increased levels of cholesterol, triacylglycerol, apo B, apo C-III and apo E, as compared to those of the chow-fed BHL rabbits. The apo E and apo C-III reached levels in the range of or even higher than those of the modified WHHL rabbits. The apo A-I levels on the other hand did not differ from those of the chow-fed rabbits. Feeding an atherogenic diet led to a decrease in the FCR of LDL to a level similar to that found in the modified WHHL rabbits.

Animals↗
PubMed1986

The standardisation of gauge length: its influence on the relative extensibility of natural and chemically modified pericardium.

Cyclic uniaxial load tests were performed on natural and chemically modified bovine pericardium which is used in the construction of heart valve substitutes. A template was employed to select specimens from the same sites in different pericardial sacs. When the pericardium was chemically modified by glutaraldehyde fixation as an entire sac the tissue showed increased extensibility after modification compared with the natural tissue. The undeformed stress-free length (gauge length) in both the natural and modified tissue was determined by a highly reproducible experimental method giving a coefficient of variation of less than 0.5%. Specimens excised from a natural pericardial sac demonstrated a significant increase (p less than 0.03) in length, 4.97 +/- 3.49%, after a single load cycle, compared with controls placed in isotonic saline but not mechanically tested. The test pieces had returned to their original length by 8.5 h after the mechanical test. After fixation the same specimens decreased significantly in length (p less than 0.001) by 11.18 +/- 4.28%. This shrinkage was not significantly different to that of the control specimens (11.09 +/- 2.47%) which had not been tested. Uniaxial loading of these chemically modified strips demonstrated a similar increase in tissue extensibility compared to the natural tissue if the undeformed length of the test specimen after shrinkage was used as the gauge length. After mechanical conditioning the chemically modified tissue also demonstrated a significant increase (p less than 0.001) in stress-free length (5.35 +/- 0.59% after 36 cycles, 8.92 +/- 1.50% after 2085 cycles). These deformations were not permanent. The tissue had returned to its original length after 38 h in its normal buffered glutaraldehyde storage medium. On the basis of these observations, recommendations for the clarification and standardisation of gauge length definitions were made in natural, chemically modified and mechanically conditioned tissue.

Animals↗
PubMed1983

The fate of autosomal modifiers of the sex-ratio trait in drosophila and other sex-linked meiotic drive systems.

A model is proposed to analyze the behavior of autosomal suppressor modifiers of "Sex-Ratio" meiotic drive in drosophila. These modifiers, if neutral in fitness, are expected to increase because they tend to be associated with the rare sex (males). However, selection operating on the sex-linked drive locus will sometimes act against autosomal modifiers as well because the two loci are always in gametic phase disequilibrium. Conditions under which modifiers will not increase are presented in terms of the relative fitness of the sex-linked drive locus. To prevent the increase of modifiers, the fitness of Sex-Ratio males relative to Standard males has to be no greater than 0.3 and there has to be overdominance in females. This model integrates findings from the search for modifiers and results from the measurement of fitness.

Animals↗
PubMed1996

Hepatocyte culture on carbohydrate-modified star polyethylene oxide hydrogels.

We describe the synthesis and in vitro biological characterization of a new class of carbohydrate-modified hydrogels based on radiation-cross-linked star polyethylene oxide (PEO). Hydrogels were synthesized from either of two types of PEO star molecules in order to vary the terminal hydroxyl content of the gels while keeping other gel properties such as molecular weight between cross-links and water content constant. The resulting gels were covalently modified with monosaccharide ligands and the behaviour of primary rat hepatocytes on the modified gels was evaluated under culture conditions. Hepatocytes exhibited a sugar-specific adhesion to the modified gels, adhering to gels bearing galactose but not glucose. Cell spreading was observed on both types of galactose-modified PEO star gels; moreover, the gels supported long-term (6 d) culture and differentiated function of primary hepatocytes. Further, on comparing the cell spreading behaviour observed on the PEO star gels with that reported previously for galactose-modified polyacrylamide, we find that our gels elicit spreading at ligand concentrations lower by an order of magnitude. A simple mechanistic analysis indicates that this enhanced ability of PEO star gels to support spreading of primary hepatocytes on low concentrations of immobilized galactose derives from freedom of the immobilized ligands to come within sufficiently close proximity to mimic a high-affinity branched oligosaccharide.

Animals↗
PubMed1991

Quantitative analysis of carbodiimide modified DNA and immunoprobing by adduct specific antibodies.

Antibodies have been raised against N-cyclohexyl-N-(4-methylmorpholinium)ethyl carbodiimide (CMC) modified single-stranded DNA and characterized by competitive and non-competitive immunoassays to be highly specific for CMC base adduct in homopolymers poly(dG), poly(dT) and DNA. The antibodies recognize picogram concentrations of CMC treated DNA with no cross reactivity to at least 1000-fold excess of unmodified DNA or CMC treated poly(dA). The detection limit of antibodies at 1.4 fmol CMC adduct allows quantitation at a CMC/base ratio of 4.6.10(-7). Based upon single modified base-containing synthetic oligomers, a 7-fold higher binding preference is observed for CMC modified thymine than guanine bases. CMC binding to supercoiled DNA is found to depend upon reaction temperature and ionic strength. CMC-modified supercoiled SV40 and ColE1 DNA, exhibit specific antibody binding proportional to the DNA concentration and extent of CMC modification. However, antibody binding observed is independent of the conformation or strandedness of CMC-modified DNA. DNA extensively modified with CMC retains its inherent capacity to specifically and quantitatively hybridize with complementary DNA immobilized to membranes upon direct blotting or Southern transfers from gels. Hybridized CMC-DNA, through antibody binding, provides for the sensitive and non-isotopic detection of the target DNA sequences.

Antibody Affinity↗
PubMed1986

Gly-Pro-Arg-Pro modifies the glutamine residues in the alpha- and gamma-chains of fibrinogen: inhibition of transglutaminase cross-linking.

During blood clotting Factor XIIIa, a transglutaminase, catalyzes the formation of covalent bonds between the epsilon-amino group of lysine and the gamma-carboxamide group of peptide-bound glutamine residues between fibrin molecules. We report that glycyl-L-prolyl-L-arginyl-L-proline (GPRP), a tetrapeptide that binds to the fibrin polymerization sites (D-domain) in fibrin(ogen), inhibits transglutaminase cross-linking by modifying the glutamine residues in the alpha- and gamma-chains of fibrinogen. Purified platelet Factor XIIIa, and tissue transglutaminase from adult bovine aortic endothelial cells were used for the cross-linking studies. Gly-Pro (GP) and Gly-Pro-Gly-Gly (GPGG), peptides which do not bind to fibrinogen, had no effect on transglutaminase cross-linking. GPRP inhibited platelet Factor XIIIa-catalyzed cross-linking between the gamma-chains of the following fibrin(ogen) derivatives: fibrin monomers, fibrinogen and polymerized fibrin fibers. GPRP functioned as a reversible, noncompetitive inhibitor of Factor XIIIa-catalyzed incorporation of [3H]putrescine and [14C]methylamine into fibrinogen and Fragment D1. GPRP did not inhibit 125I-Factor XIIIa binding to polymerized fibrin, demonstrating that the Factor XIIIa binding sites on fibrin were not modified. GPRP also had no effect on Factor XIIIa cross-linking of [3H]putrescine to casein. This demonstrates that GPRP specifically modified the glutamine cross-linking sites in fibrinogen, and had no effect on either Factor XIIIa or the lysine residues in fibrinogen. GPRP also inhibited [14C]putrescine incorporation into the alpha- and gamma-chains of fibrinogen without inhibiting beta-chain incorporation, suggesting that the intermolecular cross-linking sites were selectively affected. Furthermore, GPRP inhibited tissue transglutaminase-catalyzed incorporation of [3H]putrescine into both fibrinogen and Fragment D1, without modifying [3H]putrescine incorporation into casein. GPRP also inhibited intermolecular alpha-alpha-chain cross-linking catalyzed by tissue transglutaminase. This demonstrates that the glutamine residues in the alpha-chains involved in intermolecular cross-linking are modified by GPRP. This is the first demonstration that a molecule binding to the fibrin polymerization sites on the D-domain of fibrinogen modifies the glutamine cross-linking sites on the alpha- and gamma-chains of fibrinogen.

Animals↗
PubMed1990

Growth of Listeria monocytogenes Scott A, serotype 4 and competitive spoilage organisms in raw chicken packaged under modified atmospheres and in air.

The development of Listeria monocytogenes Scott A, serotype 4 and aerobic plate counts on minced raw chicken were determined independently at 4, 10 and 27 degrees C. Samples were packaged in flexible film under two modified atmospheres (one containing oxygen and one containing no oxygen) or air. The anaerobic modified atmosphere (75:25, CO2:N2) resulted in the failure of both the aerobic plate counts and L. monocytogenes to grow at all temperatures. Both the L. monocytogenes and aerobic plate counts grew in air at all temperatures. The aerobic modified atmosphere (72.5:22.5:5, CO2:N2:O2), which more closely duplicates commercial practice, inhibited the increase in aerobic plate counts by more than 4 log10 cfu/g compared to air at 4 degrees C. However, the L. monocytogenes was not affected by this atmosphere and increased in numbers by nearly 6 log10 cfu/g at 4 degrees C in 21 days. Regression analysis of the log10 growth and 95% confidence intervals showed that the differences between aerobic plate counts and L. monocytogenes in modified atmosphere were large. The ability of L. monocytogenes to grow in the aerobic modified atmosphere was not affected by level of the L. monocytogenes inoculum nor by the initial level of aerobic plate counts. These data show that modified atmosphere packaging of raw chicken (and probably other meats) can substantially inhibit the aerobic spoilage flora while allowing pathogenic L. monocytogenes to increase.

Animals↗
PubMed1994

The modified Liverpool total elbow prosthesis.

We present the results of the modified Liverpool total elbow joint replacement. The humeral component of the original prosthesis was modified because of a high incidence of loosening. 19 patients who had total elbow joint replacement for rheumatoid arthritis were reviewed 8 years after surgery. 14 patients had the modified prosthesis implanted. There was dramatic relief of pain and improvement in function following surgery. There was a reduced fixed flexion deformity and an increased range of movement with the modified prosthesis. None of the humeral components of the modified prosthesis have as yet required revision. In selected patients therefore, this operation is a predictably successful procedure. Our follow-up confirms the ability of the modified prosthesis to provide a pain-free, stable and mobile joint.

Aged↗
PubMed1995

Phylogenetic conservation of modified nucleotides in the terminal loop 1 of the spliceosomal U5 snRNA.

In order to study the phylogenetic conservation of modified nucleotides in the spliceosomal U5 snRNA, we determined the nucleotide sequences of the U5 snRNAs from the slime mold Physarum polycephalum (EMBL data bank accession numbers: X74440 and X74441) and we identified the pseudouridine and 2'-O-methylated residues. From a comparison of all the U5 snRNAs studied at the level of nucleotide modifications, we concluded that the modified nucleotides in U5 snRNA can be divided into three classes according to their degree of conservation: i) the modified nucleotides of the 5' terminal cap structure that display some variations from one species to the other; ii) the modified nucleotides located in the helical part of the stem/loop structure I that vary greatly in number, position and identity from one species to the other; and iii) the modified nucleotides of the terminal loop 1, that are almost identical in all the species studied. Taking into account the recent discovery of a crucial role played by this terminal loop of U5 snRNA in 5' and 3' splice site definition, we postulate that the numerous modified nucleotides it contains, five out of a total of 11, play an important role in spliceosome assembly and function. Their possible role is discussed.

Animals↗
PubMed1981

The effects of modifiers on enzyme catalysis: a non-classical nearest neighbor approach.

We present a nearest neighbor lattice model of the effects of modifiers on two-state enzyme catalysis of the reaction S in equilibrium with p. We do not in general make the assumptions of the classical approach to cooperative catalysis that yield (1) adsorption isotherms of the same form as those for the corresponding equilibrium system and (2) a rate of the catalyzed reaction proportional to the number of occupied catalytic sites. Closed form results are obtained for two approximations, the Bragg-Williams and the quasi-chemical. The latter requires (1), but is exact for several simple cases, including the concerted model, under this condition. Under (1) it is found that an interaction between modifier and catalytic sites, whether attractive or repulsive, increases the magnitudes of the slopes of the adsorption isotherms but that interactions between identical sites (catalytic or modifier) increase these magnitudes if attractive and decrease them if repulsive. Thus, the former interaction allows for phase transitions if sufficiently attractive or repulsive, but the latter only if sufficiently attractive. Herein also lies the explanation for why the concerted model displays only "positive cooperativity". It is further seen that it is not possible to classify a modifier as an activator or inhibitor of the catalyzed reaction solely on the basis of the sign of the interaction energy between catalytic and modifier sites. For a given energy, the rate of the reaction may increase or decrease in response to the modifier, or it may respond biphasically. Similarly, the rate may respond biphasically to the activities of s or p, leading to instabilities. Thus, possibilities of multiple nonequilibrium stationary states or spatio-temporal patterns are raised.

Enzymes↗
PubMed1992

HPLC determination of a chemically modified nonantimicrobial tetracycline: biological implications.

Chemically modified tetracycline (4-de-dimethylamino tetracycline), like commercially available tetracyclines, is known to inhibit experimentally induced pathologic collagen breakdown. A method for measurement of chemically modified tetracycline in small volumes (50 microliters) of rat serum was developed using reversed-phase HPLC; this was necessary because this tetracycline analog lacks antimicrobial activity and, therefore, cannot be measured with standard bioassays. This method uses the same solution for extraction and elution thus providing a simple and rapid assay for both drugs. Using this technique, the concentration of chemically modified tetracycline and tetracycline were determined in rat serum at different times after oral administration. The serum concentration of chemically modified tetracycline was much higher than that for tetracycline, and its serum half-life was greater. The IC50 of chemically modified tetracycline and tetracycline, as inhibitors of collagenase from rat polymorphonuclear leukocytes, was determined and found to be 4.1 x 10(-8) M (0.02 micrograms/ml) and 2.4 x 10(-4) M (120 micrograms/ml), respectively. Based on the serum levels of these drugs after oral administration, and their IC50 values, chemically modified tetracycline is potentially a far more potent inhibitor of excess collagenase activity than tetracycline, during pathologic conditions, and may have the added advantage of not producing some of the typical complications of long-term antibiotic therapy.

Animals↗
PubMed1995

Tumor targeting and pharmacokinetics of unmodified and modified F(ab)2 fragments of an anti-CEA murine monoclonal antibody (Immu-14).

Pharmacokinetic studies were performed with two different 111In-labeled F(ab)2 fragments of an anti-CEA murine monoclonal immunoglobulin G (Immun-14). Unmodified F(ab)2 and modified Fab-BMH-Fab fragments were compared in nude mice bearing a LS-174T human colon carcinoma tumor xenograft. Tumor accumulation is significantly higher for modified fragments than for unmodified fragments at all time points. At 24 h post injection, tumor uptake for modified and unmodified fragments reached 40 and 25% ID g, respectively. The retention of radioactivity in the liver was approx. 2-fold higher for modified fragments. Kidney uptake of modified fragments was at least 2-fold lower than that of unmodified fragments. Although blood radioactivity decreased rapidly for both fragments, the cumulative tumor activity was 40% higher for Fab-BMH-Fab fragment. Modified F(ab)2 fragments can deliver higher radiation doses to the tumor.

Animals↗
PubMed1995

Biodistribution and tumor localization of 111In-labeled unmodified and modified F(ab')2 fragments of human monoclonal IgM (16.88) in a nude mouse model.

Unmodified F(ab')2 and modified Fab'-BMH-Fab' fragments of human monoclonal IgM (16.88) were compared for biodistribution and tumor localization in nude mice bearing LS-174T human colon carcinoma xenografts. Although both unmodified and modified fragments of IgM cleared rapidly from the blood, the radioactivity retentions for each fragment in liver and kidney were significantly different. Kidney uptake of the modified fragment was about 4-fold lower than kidney uptake of the unmodified fragment. Radioactivity uptake in liver was 2-4-fold higher for the modified fragment. Lower liver and higher kidney uptake of unmodified fragments reflected the labile disulfide linkage of F(ab')2 in their hinge region and the subsequent behavior of the Fab' fragments resulting from the reduction of the disulfide linkage. Higher liver and lower kidney retention of modified fragments, on the other hand, resulted from the different cleavage mechanism of the stable thioether linkage. Tumor targeting was similar for unmodified and modified fragments at approx. 4% of injected dose per gram. These results indicate that the changes in fragment linkage chemistry may provide different pharmacokinetic patterns in vivo and improve the therapeutic application of radiolabeled fragments in human patients.

Animals↗
PubMed1997

Modified ultrafiltration attenuates dilutional coagulopathy in pediatric open heart operations.

BACKGROUND: Extreme hemodilution caused by relatively large prime volumes required for cardiopulmonary bypass in infants causes a dilutional coagulopathy, characterized by low concentrations of fibrinogen and other circulating coagulation factors. Modified ultrafiltration results in hemoconcentration and is associated with decreases in postoperative bleeding and transfusion requirements in children. This study was undertaken to quantify the effect of modified ultrafiltration on concentrations of fibrinogen, plasma proteins, and platelets in infants and small children. METHODS: Twenty patients less than 15 kg were studied. Cardiopulmonary bypass circuits were primed with crystalloid solutions. Red blood cells were added during cardiopulmonary bypass for hematocrits less than 15%. Colloid solutions were not administered. Concentrations of fibrinogen, plasma proteins, and platelets, and hematocrit were measured before cardiopulmonary bypass, before modified ultrafiltration, and after modified ultrafiltration. RESULTS: Modified ultrafiltration was associated with significant (p < 0.001) increases in hematocrit (19% +/- 6% to 31% +/- 9%), fibrinogen (65 +/- 29 to 101 +/- 45 mg/dL), and total plasma proteins (2.7 +/- 0.3 to 4.9 +/- 0.7 g/dL), but no change (p = 0.129) in platelet count. CONCLUSIONS: We conclude that modified ultrafiltration significantly attenuates the dilutional coagulopathy associated with cardiopulmonary bypass in infants.

Blood Coagulation Disorders↗
PubMed1998

Modified Konno-Rastan procedure for subaortic stenosis: indications, operative techniques, and results.

BACKGROUND: Diffuse or unresectable subaortic stenosis (SAS) necessitates an aggressive surgical approach for the elimination of left ventricular outflow tract obstruction. In this article we report our experience with the modified Konno-Rastan procedure, with inherent preservation of the native aortic valve and annulus, in the treatment of diffuse or unresectable SAS. METHODS: Sixteen children (age range, 21 months to 18 years) underwent the modified Konno-Rastan procedure through either a transventricular (n = 12) or a transatrial approach (n = 4) to the conal septum. Indications for operation were recurrent SAS (n = 3), hypertrophic obstructive cardiomyopathy (n = 3), tunnel stenosis (n = 2), SAS related to a canal (n = 3), and SAS after ventricular septal defect closure (n = 5). Eleven patients had undergone previous procedures and 5 underwent the modified Konno-Rastan procedure as their primary operation. RESULTS: The mean preoperative left ventricular outflow tract gradient of 50 +/- 17 mm Hg was reduced to 3 +/- 7 mm Hg (p < 0.001) after surgical repair. Postoperative complications included sternal infection (n = 1), heart block (n = 2), mediastinal bleeding (n = 1), and renal and cerebral ischemia (n = 1). There was 1 late postoperative death caused by pneumonia 2 years after operation (6.2% mortality rate). The mean follow-up period was 62 +/- 39 months and all patients had complete relief of preoperative symptoms and were in New York Heart Association class I. One patient underwent a successful redo modified Konno-Rastan procedure 7 years after the first operation for residual left ventricular outflow tract obstruction immediately below the aortic valve. One patient is awaiting reoperation for aortic incompetence unrelated to conal enlargement 1.5 years after the first procedure. CONCLUSIONS: The modified Konno-Rastan procedure represents an excellent therapy for diffuse or unresectable SAS in patients with a normal aortic valve. In addition, it produces excellent results in a limited number of patients with hypertrophic obstructive cardiomyopathy, in whom the Morrow procedure traditionally has been performed. Although it usually is performed through a transventricular approach, the modified Konno-Rastan procedure also can be performed through a transatrial approach; this is particularly useful in patients who have had previous ventricular septal defect closure associated with SAS occurring proximal to the prosthetic patch.

Adolescent↗