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In vitro enzymatic recognition of DNA modified by O,O'-diacetyl or O-acetyl derivatives of the carcinogen 4-hydroxyaminoquinoline-1-oxide.

Purified DNA was modified in vitro by 3H-labelled O-acetyl or O,O'-diacetyl-4-hydroxyaminoquinoline-1-oxide (Ac4HAQO or di Ac-4HAQO). It was then subjected to the action of the single-stranded DNA specific nuclease S1 and the digested fractions were analysed. For both types of modified DNA, the release of non-modified nucleotides was faster than the release of modified nucleotides. This result is at variance with that obtained with acetoxy-acetylaminofluorene-modified DNA: in the latter case, the modified nucleotides were preferentially released. The results suggest that the S1 endonuclease can recognize different conformational changes in DNA, which depend on the carcinogen used. The enzymatic activity (or activities) present in Micrococcus luteus cell extracts released ethanol-soluble products from Ac-4HAQO modified DNA.

4-Hydroxyaminoquinoline-1-oxide

Interlaboratory comparison of antisera and immunoassays for benzo[a]pyrene-diol-epoxide-I-modified DNA.

An interlaboratory comparison of immunoassays using antisera elicited against benzo[a]pyrene-diol-epoxide-modified DNA (BPDE-I-DNA) was carried out resulting in standardization of antisera, competitors and assay conditions. The assays used included competitive enzyme-linked immunosorbent assays (ELISA) with color and fluorescence endpoint detection and an ultrasensitive enzyme radioimmunoassay (USERIA) with a radioactive endpoint. Three different antisera were compared, two of which were obtained from different rabbits immunized with the same BPDE-I-DNA and a third from an animal immunized with another BPDE-I-DNA sample. Samples of standardized BPDE-I-DNA with high (36 pmol adduct/microgram DNA; 1.2 adducts/10(2) nucleotides) and low (4.5 fmol/microgram DNA; 1.5 adducts/10(6) nucleotides) modification levels were prepared and used in each laboratory. The antisera were all elicited against DNAs modified to a high extent, and it was therefore not surprising that they detected adducts in a slightly modified DNA sample with lower efficiency than those in highly modified DNA samples. The discrepancy of antibody recognition between the highly and slightly modified samples varied between 1.4- and 11.2-fold depending on the antiserum and assay. To ascertain the quantitative capability of the immunoassays, the modification level of DNA isolated from mouse keratinocytes treated with [3H]benzo[a]pyrene was determined by radioactivity and immunoassay. These results indicated that when a biological sample is assayed against a BPDE-I-DNA standard modified in the same range as the biological samples (4.5 fmol/microgram), quantitative recovery of adducts is achieved by immunoassay. These studies resulted in the realization that interlaboratory differences in immunoassay procedure can have significant consequences for data comparison and that where possible it is preferable for laboratories to use the same antisera and modified DNA standards.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide

Dosage-dependent modifiers of position effect variegation in Drosophila and a mass action model that explains their effect.

Twelve dominant enhancers of position effect variegation, representing four loci on the second and third chromosomes of Drosophila melanogaster, have been induced by P-element mutagenesis. Instead of simple transposon insertions, seven of these mutations are cytologically visible duplications and three are deficiencies. The duplications define two distinct regions, each coinciding with a locus that also behaves as a dominant haplo-dependent suppressor of variegation. Conversely, two of the deficiencies overlap with a region that contains a haplo-dependent enhancer of variegation while duplications of this same region act to suppress variegation. The third deficiency defines another haplo-dependent enhancer. These data indicate that loci capable of modifying variegation do so in an antipodal fashion through changes in the wild-type gene copy number and may be divided into two reciprocally acting classes. Class I modifiers enhance variegation when duplicated or suppress variegation when deficient. Class II modifiers enhance when deficient but suppress when duplicated. From our data, and those of others, we propose that in Drosophila there are about 20 to 30 dominant loci that modify variegation. Most appear to be of the class I type whereas only two class II modifiers have been identified so far. From these observations we put forth a model, based on the law of mass action, for understanding how such suppressor-enhancer loci function. We propose that each class I modifier codes for a structural protein component of heterochromatin and their effects on variegation are a consequence of their dosage dependent influence on the extent of the assembly of heterochromatin at the chromosomal site of the position effect. It is further proposed that class II modifiers may inhibit the class I products directly, bind to hypothetical termination sites that define heterochromatin boundaries or promote euchromatin formation. Consistent with our mass action model we find that combining two enhancers together produce additive and not epistatic effects. Also, since different enhancers have different relative strengths on different variegating mutants, we suggest that heterochromatic domains are constructed by a combinatorial association of proteins. The mass action model proposed here is of general significance for any assembly driven reaction and has implications for understanding a wide variety of biological phenomena.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Conformations of poly(dG-dC).poly(dG-dC) modified by the O-acetyl derivative of the carcinogen 4-hydroxyaminoquinoline 1-oxide.

Poly(dG-dC).poly(dG-dC) has been modified by reaction with 4-acetoxyaminoquinoline 1-oxide (Ac-4 HAQO), the ultimate carcinogen of 4-nitroquinoline 1-oxide. The circular dichroism (CD) spectra of the modified and unmodified polymers have been compared under various experimental conditions. The CD spectra were recorded in 1 mM phosphate, 50% (v/v) ethanol, 3.8 M LiCl and 95% (v/v) ethanol, conditions in which poly(dG-dC).poly(dG-dC) adopts the B-, Z-, C- and A-form respectively. In 1 mM phosphate buffer, poly(dG-dC).poly(dG-dC) modified by Ac-4 HAQO seems not to contain regions in the Z-form. Z-form induction could be progressively obtained by the addition of ethanol as follows: in the buffer with about 30% ethanol the modified polymer started to adopt the Z structure, while 40% of ethanol in the buffer was necessary for the unmodified polymer. In the 50% ethanol-1 mM phosphate buffer mixture (v/v), poly(dG-dC).poly(dG-dC) was entirely in the Z-form while poly(dG-dC).poly(dG-dC) modified by Ac-4 HAQO remained partially in the B-form. Enzymatic digestions with the nuclease S1 which is specific of the single-stranded DNA were carried out in order to support the modified poly(dG-dC).poly(dG-dC) CD study conclusions. The role played by the two major adducts on the conformational characteristics of modified polymer is discussed.

Aminoquinolines

Separation of SH-modified myosin subfragment-1 (A1) isozyme into two distinct equimolar fractions by an affinity chromatography.

Our previous kinetic studies indicated that SH-modified myosin subfragment-1 A1 isozyme (S1(A1] contains at least two different types of active sites (Emoto, Y., Kawamura, T., & Tawada, K. (1985) J. Biochem. 98, 735-745). In those studies we have modified highly reactive SH-groups in S1(A1) with thimerosal. In this work, we separated the modified S1(A1) into two equimolar fractions by affinity chromatography with agarose-ADP. For the separation, Mg2+ in the elution buffer was indispensable. Although the two fractions appeared to have the same number of modified SH-groups per mol of S1, they had different enzymic and fluorescent properties. SH-modification with an excess of thimerosal for a much longer duration did not change any of the results: not the chromatographic profile, the properties of the two fractions, nor the number of modified SH-groups. Hence the two different populations were not generated by incomplete modification. After reduction with dithiothreitol, however, the differences between the two fractions disappeared. When we separately re-modified the reduced fractions and re-chromatographed them, in each case we again obtained two fractions, which had the same properties as the two fractions obtained from the original modification with thimerosal. These results demonstrate that the active site heterogeneity in SH-modified S1(A1) had no intrinsic origin in the unmodified S1: it was introduced by the SH-modification, but by an unknown mechanism(s) other than incomplete modification.

Adenosine Triphosphatases

Serial subcultivation of Giardia lamblia in Keister's modified TYI-S-33 medium containing ultroser G.

The ability of Giardia strains of the duodenalis type to grow in Keister's modified TYI-S-33 medium varies with serum lot. Recently, strains of Giardia including MR4, WB, and Human-1-Portland, have been cultivated in Keister's modified TYI-S-33 medium containing the serum substitute Ultroser G and have been cultured serially as least 40 times. An optimal concentration of 8% Ultroser G promotes maximal growth in Keister's modified TYI-S-33 medium for all three strains. This concentration of Ultroser G will produce a two-log increase in the number of trophozoites in approximately three days post-inoculation. Generation times for the trophozoites ranging from 6 to 11 h have been achieved in Keister's modified TYI-S-33 containing 10% adult bovine serum and from 8 to 13 h in Keister's modified TYI-S-33 with 8% Ultroser G. Despite the excellent growth of Giardia strains in medium containing Ultroser G, the maximum trophozoite density is only about half of that achieved in Keister's modified TYI-S-33 medium supplemented with 10% adult bovine serum. Comparisons of trophozoites grown with serum or the serum substitute reveal no discernable differences in morphology and motility. Additionally, these strains have been successfully cryopreserved and revived in Keister's modified TYI-S-33 medium supplemented with Ultroser G. Because Ultroser G is a characterized mixture of six main groups of ingredients (growth factors, adhesion factors, mineral trace elements, hormones, binding proteins, and vitamins), the variability in cell proliferation that may occur when changing serum lots should be minimized when using this product.

Animals

Identification of Salmonella somatic and flagellar antigens by modified serological methods.

This report describes two modified methods for the identification of Salmonella somatic (O) and flagellar (H) antigens. Over a period of 2 years, both modified methods were found to be approximately three times less labor intensive than the standard methods while requiring no more technical skill. The modified methods were as accurate as the standard methods in identifying the O and H antigens of 350 Salmonella isolates. Furthermore, 43 O antisera reacted exclusively with organisms possessing homologous O antigens when the modified and two standard methods were used. At the antiserum dilutions used for H antigen identification, H antisera did not react with O antigens or heterologous H antigens by either the modified or the standard method. Compared with the standard method for H antigen identification, the modified method was approximately 20 times more economical with respect to antisera and usually generated a 1.5- to 4-fold higher titer. Since the antisera stored for use in the modified method for H antigen identification were usually 100-fold more dilute than the antisera stored for the standard method, an antibody-stabilizing buffer was incorporated in the diluted antisera, allowing these reagents to be used for at least 9 to 16 months.

Agglutination Tests

Outer membrane of Pseudomonas aeruginosa: heat- 2-mercaptoethanol-modifiable proteins.

A number of polyacrylamide gel systems and solubilization procedures were studied to define the number and nature of "major" polypeptide bands in the outer membrane of Pseudomonas aeruginosa. It was shown that five of the eight major outer membrane proteins were "heat modifiable" in that their mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was determined by the solubilization temperature. Four of these heat-modifiable proteins had characteristics similar to protein II of the Escherichia coli outer membrane. Addition of lipopolysaccharide subsequent to solubilization caused reversal of the heat modification. The other heat-modifiable protein, the porin protein F, was unusually stable to sodium dodecyl sulfate. Long periods of boiling in sodium dodecyl sulfate were required to cause conversion to the heat-modified form. This was demonstrated both with outer membrane-associated and purified lipopolysaccharide-depleted protein F. Furthermore, lipopolysaccharide treatment had no effect on the mobility of heat-modified protein F. Thus it is concluded that protein F represents a new class of heat-modifiable protein. It was further demonstrated that the electrophoretic mobility of protein F was modified by 2-mercaptoethanol and that the 2-mercaptoethanol and heat modification of mobility were independent of one another. The optimal conditions for the examination of the outer membrane proteins of P. aeruginosa by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis are discussed.

Bacterial Proteins

A modified procedure for simultaneous extraction and subsequent assay of calcium-dependent and lysosomal protease systems from a skeletal muscle biopsy.

An extraction and assay system was developed for quantifying endogenous muscle proteases from a single 5-g sample. A single extraction buffer was developed for simultaneous extraction of both calcium-dependent proteases (CDP) and cathepsins. Protease activity determined by the modified procedure was compared to standard procedures currently used in our laboratory. The successful use of the modified procedure on muscle biopsies was verified. Activities per gram of ovine longissimus muscle of CDP system components for 50-g standard and 5-g modified procedures were not different (P greater than .05) for CDP-I (1.16 vs 1.08), CDP-II (.89 vs 1.03), or CDP inhibitor (2.34 vs 2.32), respectively. Activities of cathepsins per gram of muscle for standard and modified procedures were higher (P less than .05) for the modified procedure (cathepsins B + L, 202.0 vs 309.8), but not different (P greater than .05) for cathepsin B (76.6 vs 98.8). Cystatin-like activity was not different (P greater than .05; 3.4 vs 3.2). To test the effect of location within the longissimus muscle on protease activities, 5 g of longissimus muscle was removed immediately postmortem from each of six locations from each side of three steer carcasses. Location within the longissimus muscle had no effect (P greater than .05) on the protease activities measured. Protease activities determined on bovine longissimus muscle biopsies with the modified procedure were similar to immediate postmortem activities. These data verify that the modified procedure was as able to quantify endogenous muscle proteases as the standard procedures and could be used on muscle biopsies. This procedure should be useful in studying the role of endogenous muscle proteases in muscle growth and postmortem proteolysis.

Animals

Control release of prostaglandin E2 from polylactic acid microcapsules, microparticles and modified microparticles.

Low molecular weight polylactic acid (PLA) microparticles containing prostaglandin E2 were prepared. An average particle size of 30 micron was obtained by grinding at low temperature. These particles were further treated by heating to modify the shape and the release pattern. Microscopic studies showed that the modified particles had a smoother surface than the non-modified particles. The drug was also incorporated into PLA microcapsules using the solvent evaporation process, but the incorporation efficiency was lower. We studied the release profiles of modified particles prepared using different molecular weight PLA. The release rate depended on the molecular weight with lower molecular weights having a greater release rate. In addition, the release studies showed different matrix forms made from the same molecular weight PLA had different release patterns. For example, the microcapsules released the drug very slowly whereas the modified particles exhibited a moderate release rate. It was also noted that the matrix release model could describe the release patterns of microcapsules and modified particles very well. However, the release patterns of non-modified microparticles did not follow this model.

Capsules

Treatment of carcinoma of the breast by modified radical mastectomy.

To evaluate the results of treatment of Stage I and Stage II-T1 and T2, NO and N1-carcinoma of the breast by modified radical mastectomy with preservation of the pectoralis major muscle, the survival rates of all such patients treated by the senior author from 1965 through 1968 were compared with the survival rates of a simultaneous group of patients with similar stage disease treated by conventional radical mastectomy by the same surgeon. There were a total of 134 patients, of whom 51 had modified radical mastectomy and 83 conventional radical mastectomy. The five year survival rate for those treated by standard radical mastectomy was 81 per cent, and for those treated by modified radical mastectomy, it was 84 per cent. In patients with histologically negative axillary lymph nodes, the rates were 86 per cent following both radical mastectomy and modified radical mastectomy. Four per cent of the surviving patients after modified radical mastectomy and 7 per cent of the five year survivors after radical mastectomy had evidence of metastases at five years. Locally recurrent disease was noted in 5 per cent of those who had modified radical mastectomy and 7 per cent of those who underwent standard radical mastectomy. This analysis demonstrates that there is no significant difference in the survival and recurrence rates after conventional radical mastectomy and ,odified radical mastectomy of the Patey type. There is a high incidence of recurrence-free survival after both of these operations. Since modified radical mastectomy is less traumatic, involving less damage to muscular tissues, and is followed by significantly decreased deformity, it is advised as the treatment of choice for patients with carcinoma of the breast having no or minimal evidence of axillary node involvement. More extensive tumors adherent to the pectoral fascia or associated with multiple or large palpable axillary nodes should still be treated by conventional radical mastectomy.

Adult

Mixed lymphocyte reactivity and cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes in C57BL/10 congenic and B10-A recombinant mouse strains.

Cell-mediated lympholysis (CML) to trinitrophenyl (TNP)-modified autologous splenic lymphocytes has been recently reported in the mouse (1). Both the sensitization and effector phases of this phenomenon were shown to be T-cell mediated. Effector cell specificity studies indicated that modification of the target cells is a necessary but insufficient requirement for cytolysis, and suggested that altered cell surface components controlled by genes mapping in the mouse major histocompatibility H-2 complex (MHC) are important in the specificity of the cytotoxic reaction (1). In allogeneic models the generation of cytotoxic effector cells has been shown to be preceded or accompanied by immunogen- induced proliferation of responding lymphocytes, i.e. a mixed lymphocyte reaction (MLR) (2-5), although the generation of effectors may not necessarily always be the consequence of extensive cell proliferation (5). If the induction of cytotoxic effector lymphocytes by modified syngeneic spleen cells is characteristic of sensitization with cellular alloantigens, one would expect to find that sensitization with TNP-modified autologous cells would also induce thymidine incorporation by the responding cells in the culture. The present report demonstrates that both stimulation of thymidine incorporation and generation of cytotoxic effector cells are part of the in vitro response to TNP-modified autologous lymphocytes. However, the MLR to TNP- modified autologous cells consistently appeared to be less pronounced when compared with an allogeneic MLR, whereas the cytotoxic activity of the effector cells generated by sensitization against TNP-modified autologous cells was frequently as high as that detected against H-2 alloantigens. These two components of reactivity to "modified self" are verified in several C57BL/10 congenic and B10.A recombinant mouse strains.

Animals

Respiratory tract gene transfer. Transplantation of genetically modified T-lymphocytes directly to the respiratory epithelial surface.

To evaluate the strategy for potentially treating respiratory disorders with genetically modified T-lymphocytes, the interleukin-2 (IL-2)-dependent murine T-cell line, CTLL2, was genetically altered with the Escherichia coli beta-galactosidase (beta-gal) gene (lacZ) in vitro with a retroviral vector and the modified T-cells were transplanted directly to the respiratory epithelial surface of syngeneic C57Bl/6 mice. Southern and Northern analyses confirmed that the neomycin-selected modified T-cells contained and expressed the lacZ gene. The fate of the modified T-cells (CTLL2/lacZ) was followed by flow cytometry with T-cell surface marker Thy1.2 and fluorescent beta-gal analysis. One day after transplantation (7.5 x 10(5) CTLL2/lacZ T-cells/g of body weight), 95 +/- 3% of the Thy1.2+ T-cells recovered from respiratory epithelial lining fluid (ELF) were beta-gal+. Importantly, the modified T-cells remained in the lung for some time; at 3 days, Thy1.2+ beta-gal+ T-cells represented 63 +/- 12% of ELF Thy1.2+ T-cells and 59 +/- 6% of Thy1.2+ T-cells recovered from the whole lung. At 7 days, 33 +/- 8% of the Thy 1.2+ cells in ELF and 75 +/- 6% of the Thy1.2+ cells in whole lung were Thy1.2+ beta-gal+. In contrast, the proportion of the Thy1.2+ beta-gal+ T-cells in the spleen, the major extrapulmonary lymphatic organ, never rose above 3 +/- 1% of the total Thy1.2+ cells. The number of Thy1.2+ beta-gal+ T-cells in the lung could be modified by the systemic administration of IL-2, with whole lung Thy1.2+ beta-gal+ T-cells increasing 4.6-fold 3 days after transplantation, compared with non-IL-2-treated animals. These studies suggest that direct transplantation of genetically modified T-cells into the lung is feasible and represents a viable strategy for lung-specific gene transfer.

Animals

A double-monoclonal immunoenzymometric assay for alpha 1-fetoprotein modified for increased analytical precision.

We modified a one-step, two-site, double monoclonal immunoenzymometric assay (Abbott Laboratories) for serum alpha1-fetoprotein (AFP) to increase its sensitivity and improve test precision at the low end. We increased sample size, incubation interval, and reaction time and temperature, and decreased the final reaction volume. Interassay CVs for the modified method ranged from 6.2 to 8.0% for mean concentrations of AFP in serum of 5.2 to 34.2 micrograms/L--substantially better than those for the unmodified monoclonal method--and agreed well with those of the comparison method (modified Abbott polyclonal immunoenzymometric assay). AFP values by the modified monoclonal procedure (y) correlated well with results by the polyclonal method (x): y = 0.983x + 1.84 micrograms/L (r = 0.927, n = 59). The detection limit of the modified monoclonal test was 0.2 microgram/L, as compared with 1.0 and 1.4 micrograms/L, respectively, for the modified polyclonal and the unmodified monoclonal procedures. We recommend using the modified monoclonal method for monitoring cancer patients with low tumor burden.

Antibodies, Monoclonal

T cell responses induced by the parenteral injection of antigen-modified syngeneic cells. I. Induction, characterization, and regulation of antigen-specific T helper cells involved in delayed-type hypersensitivity responses.

This report presents evidence for the role of antigen-specific helper T cells in augmenting the in vivo development of delayed-type hypersensitivity (DTH) responses to both hapten and protein antigens. The role of these helper T cells in the in vivo induction and regulation of DTH responses was investigated. Mice were primed subcutaneously with optimal numbers (3 X 10(7)) of either protein antigen- or TNP-modified syngeneic spleen cells. Primed spleen or lymph node cells, but not thymocytes or unprimed cells, were found to significantly augment the DTH response of syngeneic recipients injected subcutaneously with suboptimal numbers (1 to 2 X 10(6)) of antigen-modified syngeneic cells. Primed spleen or lymph node cells augmented both in vivo ear swelling reactions and in vitro antigen-induced T cell proliferative responses in recipient animals. The helper effect was found to be mediated by a population of radioresistant, Thy-1+, Lyt-1+2-, I-A+ cells, a phenotype identical to that of antigen-specific Tprlf cells found in primed lymph nodes. In contrast, effector TDH cells were found to be Thy-1+, Lyt-1+2-, I-A- cells. Splenic T cells from TNP-primed mice augmented TNP-specific DTH responses, but not DTH to irrelevant protein antigens, and vice versa. Helper T cell induction correlated with the presence of H-2 I-region determinants on the inducer cells, because antigen-modified spleen cells were the most efficient inducers, modified thymocytes were less efficient, and modified erythrocytes were ineffective. Mapping studies also indicated that I-region identity between the antigen-modified spleen cell immunogen and the Th donors was both necessary and sufficient for DTH Th cell induction. In addition, functional helper T cell activity could be both specifically tolerized and suppressed by the transfer or suppressor T cells raised by the i.v. injection of antigen-modified syngeneic cells.

Animals

[Effect of tyrosine-74-modified cytochrome C on electron transfer in Keilin-Hartree submitochondrial particles].

The tyrosine-74 modified cytochrome c is obtained by the interaction of cytochrome c with N-(2, 2, 5, 5-tetramethyl-3-carboxy-piroline-oxyl) Imidazol. The absorbtion spectrum of the modified derivative at the visible region does not differ substantially from the native protein. The band of absorbtion at 695 nm, which shows that the performed modification is soft and the conformation of the modified cytochrome c is close to that of the native protein. Redox potential of the modified cytochrome c, determined by spectrophotometric titration, does not differ from that of the native protein. Submitochondrial particles, deficient of cytochrome c, are reconstructed with modified protein. In both substrates of biologic oxidation succinate and ascorbate the electron transport is restored by the modified protein in considerably higher concentrations than those of the native cytochrome c. Inspite of small conformation differences and unchanged redox potential of the modified cytochrome c substantial differences are observed in its electron-carrying properties as well as its interaction with the membrane cytochrome c reductase and oxydase.

Animals

Hemodynamic and clinical comparison of the Hancock modified orifice and standard orifice bioprostheses in the aortic position.

Bioprosthetic aortic valve replacement in patients with a small aortic root has been associated with postoperative transvalvular gradients. A modified orifice Hancock xenograft bioprosthesis has been developed and is purported to increase significantly the effective orifice area (as evaluated by in vitro testing) compared to the standard orifice Hancock bioprosthesis. To assess the in vivo differences, we compared 481 patients with standard orifice prostheses with 156 patients with modified orifice prostheses. Postoperative catheterization was performed in 24 patients with modified orifice (valve diameters 19 to 25 mm) with 14 with standard orifice valves (valve diameters 21 to 25 mm). Actuarial rates of survival, valve failure, endocarditis, and thromboembolism did not differ significantly between the two subgroups. Peak aortic valve gradients on the whole were less in the modified orifice subgroup than in the standard origice subgroup (12 +/- 1 torr versus 20 +/- 6 torr [mean +/- SEM]), but the difference was not statistically significant (p greather than 0.05). The calculated in vivo aortic valve areas were slightly, but insignificantly, greater in the modified orifice subgroup than in the standard orifice subgroup (p greater than 0.05). These in vivo data partially corroborate the in vitro findings of increased effective orifice area and internal-to-external diameter ratio for the modified orifice bioprosthesis. The hemodynamic differences between the two valve types are small, however, and the putative clinical advantages inherent in the use of the modified orifice bioprosthesis remain to be completely defined.

Aortic Valve

A prospective trial comparing the efficacy and complications of the modified Dornier HM3 and MFL 5000 lithotriptors for solitary renal calculi.

A prospective randomized study of 198 patients was conducted to compare the efficacy of the modified Dornier HM3 lithotriptor to the MFL 5000 lithotriptor. Entrance criteria included solitary stones at any location within the upper collecting system that had not previously been treated with lithotripsy. Following lithotripsy the patients were evaluated by a blinded radiologist with a plain abdominal film, tomograms and renal ultrasound at 1, 4 and 12 weeks. Patients were classified at 12 weeks after lithotripsy as failing treatment if any stone fragments were imaged. Of the patients 170 were available for complete 3-month followup. No statistical or clinical difference in stone-free rates was apparent for calculi in the ureter or renal pelvis in either group. Of patients with lower caliceal stones 80% had no residual fragments visualized at 12 weeks when treated with the modified HM3 device versus 56% with the MFL 5000 lithotriptor (p = 0.05). Treatment time on the MFL 5000 unit was significantly prolonged compared with the modified HM3 device (0.7 hours versus 0.4 hours, respectively) resulting in fewer patients being treated in a given day (p < 0.001). No statistical difference in complication rates could be found between the 2 machines. Steinstrasse were noted in 10% of the patients treated with the modified HM3 device and 6% of the MFL 5000 group. Subcapsular hematomas were noted in 4% of the MFL 5000 treatment arm compared to 1% in the modified HM3 group. Overall, the MFL 5000 lithotriptor was believed to offer no significant clinical advantage over the modified HM3 device in terms of lithotripsy efficacy, although the multifunctional table did offer more versatility for stone treatment. For a busy lithotripsy center, the modified HM3 lithotriptor is still the most efficacious.

Adult