Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “modified”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources

The sinotubular junction does not progressively dilate four years after modified subcoronary freestyle stentless tissue aortic valve replacement.

BACKGROUND AND AIM OF THE STUDY: Aortic root dilation at the sinotubular junction (STJ) results in aortic regurgitation associated with normal valves and with a complete subcoronary stentless aortic bioprosthesis. The study aim was to assess for progressive aortic root dilation following modified subcoronary Freestyle aortic valve replacement (AVR), and to compare for differences between implant techniques. METHODS: Aortic root diameter was measured at the annulus, sinuses of Valsalva, STJ and tubular aorta on post-pump transesophageal echocardiograms and on early (3-month) and late (>2 years) transthoracic echocardiograms among 16 patients after modified subcoronary Freestyle valve replacement, 16 after root inclusion, and three after total root replacement. RESULTS: Mean follow up was 3.9 +/- 0.8, 3.3 +/- 0.7 and 3.5 +/- 1.1 years for modified subcoronary, root inclusion and total root patients, respectively. The aortic annulus, sinuses and STJ increased in diameter to similar extents between surgery and three months after modified subcoronary and root inclusion surgery, with no further increase at late follow up (modified subcoronary STJ 18.4 +/- 3.7, 21.1 +/- 3.7 and 20.5 +/- 4.4 mm on intraoperative, early and late echocardiography, respectively; root inclusion STJ 21.8 +/- 3.9, 25.4 +/- 4.6 and 24.4 +/- 4.4 mm, respectively). There were no changes in aortic root diameter after total root replacement (STJ 23.7 +/- 1.2 and 25.7 +/- 6.0 on intraoperative and late follow up, respectively). Aortic regurgitation prevalence was low, and similar between groups. CONCLUSION: Small but significant increases in aortic root dimensions were seen during the first three months after modified subcoronary and root inclusion surgery, with no subsequent change. The early changes were likely caused by resorption of paravalvular edema and hematoma transiently affecting aortic root measurements in the perioperative period. There was no evidence of progressive STJ dilation at 3.9 years after modified subcoronary Freestyle AVR.

Aged↗

[Modified Madigan prostatectomy].

OBJECTIVE: To improve Madigan prostatectomy (MPC) for a much satisfactory effect in open surgery. METHODS: A total of 52 patients with benign prostatic hyperplasia (BPH) were treated using MPC. The MPC procedure was modified by exposing anterior prostatic urethra near the bladder neck and conjunction with cystotomy. This modified procedure preserved prostatic urethra intact and could also deal with intracystic lesions at the same time. RESULTS: The intact of prostatic urethra was kept completely or almost for 48 cases. The hemorrhage amount during modified procedure was a less. The mean operative time was 120 minutes. The 35 patients had been followed up for 1 - 12 months. The average Qmax was 18.9 ml/s. The cystourethrography revealed that the urethra and bladder neck were intact in 8 patients postoperatively. Furthermore, the prostatic urethra was obviously wider after modified MPC. CONCLUSIONS: The modified MPC can reduce the urethra injury and enlarge the MPC indications. The modified technique is easy to perform with little complications and much more satisfactory clinical result. The modified MPC is highly recommended.

Aged↗

Improved activity and stability of alkaline phosphatases from psychrophilic and mesophilic organisms by chemically modifying aliphatic or amino groups using tetracarboxy-benzophenone derivatives.

The activity-stability-structure relationship of the cold-active alkaline phosphatase from Red Arctic shrimp, Pandalus borealis (SAP) was studied by chemically modifying aliphatic (C-H) or amino (NH2) groups using benzophenone tetracarboxylic derivatives in either a light (UV-A) or dark reaction. The response of the cold-adapted enzyme was compared to a similarly modified calf alkaline phosphatase (CAP). MALDI-TOF-MS was used to determine the extent and nature of the modifications in both SAP and CAP. On average 2 to 4 amino acid residues were linked to a BP-modifier, with up to 18 to 21 amino acids modified in a smaller portion of the material. The effect of the modifications on kinetic and thermodynamic properties varied with the enzyme and type of modification. The aliphatic-group modified SAP demonstrated typical characteristics of a mesophilic enzyme, consistent with an activity-stability trade-off where gain in thermostability was attained at the expense of decreased activity. In contrast, the activity of the amino-group modified SAP attained an even more psychrophilic character with respect to its kinetic (increase in kcat and Km) and thermodynamic (reduction in deltaH#) properties. Interestingly, the amino-group modified SAP also acquired higher thermostability, thus demonstrating that both activity and stability can be simultaneously enhanced using chemical modification. The study demonstrates the applicability of benzophenone chemical modification for improving the thermal properties of enzymes from psychrophiles and mesophiles.

Alkaline Phosphatase↗

[Comparison of antitumor effects of dendritic cells modified with different forms of hepatocellular cancer antigens].

AIM: To explore the antitumor effects of dendritic cells (DCs) modified with different forms of hepatocellular cancer antigens. METHODS: DCs were modified with freeze-thawed H22 cell lysate, small molecular H22 peptides and Hsp70-H22 peptide complex, respectively. The cytotoxicity of DCs-activated CTLs to H22 cells was detected by MTT colorimetry. The expression level of IFN-gamma mRNA in splenocytes was detected by RT-PCR. The DCs modified with different antigens were used to immunize mice and then the suppressive effects on the growth of tumor were measured. RESULTS: The DCs modified with H22 peptides alone could not activate CTLs. The ability to activate CTLs by DCs modified with Hsp70-H22 peptide complex was stronger than that by DCs modified with freeze-thawed H22 lysate, with the killing rates of CTLs being 47.3% and 18.3%, respectively. The expression level of IFN-gamma mRNA in 3 groups of splenocytes was consistent with the killing rate of CTLs.The growth of H22 cells in mice immunized with DCs modified with freeze-thawed H22 lysate or Hsp70-H22 peptide complex was suppressed, but the suppressive effect of the latter was stronger than that of the former. The tumorigenesis rate in the Hsp70-22 peptide complex group was only 40%, whereas the tumorigenesis rates in the other two groups were 100%. CONCLUSION: Hsp70-H22 peptide complex is a strong sensitizer for DCs, which participates in immune rejection of tumor through activating CTLs and inducing CD4 (+) T cells to differentiate into Th1 cells.

Animals↗

[Enhancing effect of Ulex europaeus agglutinin I modified liposomes on oral insulin absorption in mice].

AIM: To investigate the enhancing effect on insulin absorption through GI. tract in mice by using the Ulex europaeus agglutinin I (UEA1) modified liposomes as the carrier. METHODS: UEA1 modified phosphatidylethanolamine (PE) was prepared by conjugating method of 1-ethyl-3-(3'-dimethylaminopropyl) carbodiimide (EDC), then the modified compound (PE-UEA1) was incorporated into the conventional liposomes of insulin to obtain UEA1 modified liposomes. The agglutination test was performed to examine the UEA1 biological activities after synthesis and modification. When liposomes were applied to healthy mice or diabetic mice at insulin dose of 350 u x kg(-1) orally, the hypoglycemic effect was investigated according to the blood glucose level determination. RESULTS: The blood glucose levels of the healthy mice reduced by UEA1 modified liposomes were (84 +/- 15)% at 4 h, (78 +/- 11)% at 8 h and (90 +/- 12)% at 12 h after oral administration. The conventional liposomes and saline showed no effect. The blood glucose levels of the diabetic mice reduced by UEA1 modified liposomes were (73 +/- 7)% at 4 h, (74 +/- 9)% at 8 h, (86 +/- 9)% at 12 h after oral administration. CONCLUSION: The UEA1 modified liposomes promote the oral absorption of insulin due to the specific-site combination on M cell membrane.

Administration, Oral↗

[Selective determination of dopamine in the presence of high concentration of ascorbic acid with L-cysteine modified glassy carbon electrodes].

OBJECTIVE: To establish an assay system for determination of dopamine (DA) in the presence of ascorbic acid (AA) with L-cysteine modified glassy carbon electrode. METHODS: L-cysteine was modified onto glassy carbon electrode electrochemically, and with this modified electrode, dopamine was determined by linear sweep stripping voltammetry. RESULTS: L-cysteine polymer-modified electrode had strong catalytic effect towards the electrochemical oxidation of DA. The modified electrode showed good properties in determination of DA with coexisting AA. Under selected conditions, the linearity of DA was in the range of 2.0 x 10(-7) - 1.0 x 10(-4) mol/L with the detection limit of 2.0 x 10(-8) mol/L. The stability, reliability and recovery of this L-cysteine-modified electrode based on electrochemical method were also satisfactory. CONCLUSION: L-cysteine-modified electrode can avoid the interference by AA for determination of DA.

Ascorbic Acid↗

[Cellular uptake and cytotoxicity of modified chitosans as gene carriers].

OBJECTIVE: To evaluate the effects of arginine modified chitosan or hexadecylated modified chitosan as gene carriers on the cellular uptake by vascular smooth muscle cells and its in vitro cytotoxicity. METHODS Plasmid DNA was labeled with alpha-32P-dATP and complexed with the modified chitosans or unmodified chitosan to form nanoparticle complexes by complex coacervation method. Uptake of all kinds of chitosan/ DNA nanoparticle complexes (CNC) by A10 cells was measured by beta-liquid scintillation counting. The in vitro cytotoxicity of the CNC was evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. RESULTS: The diameters of the CNC ranged from 55.9-174.9 nm and the zeta potentials were from 10. 8 mV for the arginine modified chitosan/DNA nanoparticle complexes (ACNC) to 1.8 mV for the hexadecylated chitosan/DNA nanoparticle complexes (HCNC). The cellular uptake of the modified chitosan/ DNA nanoparticle complexes (MCNC) by A10 cells increased significantly when compared with the unmodified chitosan/DNA nanoparticle complexes (UCNC) (P < 0.05), with the HCNC at N/P ratio of 1:1 and the ACNC at ratio of 8:1 showing the highest cellular uptake (1.3 fold higher than UCNC, P < 0.05). MCNC were much less cytotoxic when compared with Lipofectamine 2000-DNA nanoparticles. CONCLUSION: DNA nanoparticle complexes prepared with either arginine or hexadecylated modified chitosan can improve the cellular uptake of the DNA, while the in vitro cytotoxicity of both of the modified chitosan is much less than that of Lipofectamine 2000.

Animals↗

[In vitro anti-tumor effect of CTL induced by HSP70-Id complex-modified dendritic cells].

OBJECTIVE: To prepare the tumor antigen peptide complex (HSP70-1d) of HSP70 and idiotype (Id) from SmIg ScFv fragment in patients with Chronic B cell leukemia (B-CLL), and to study the anti-tumor effect of cytotoxic T lymphocyte (CTL) induced by HSP70-Id complex-modified dendritic cell (DC) in vitro and explore their immune mechanism. METHODS: Purified HSP70 was combined into peptide complex (HSP70-Id) with the prepared Id-ScFv from B-CLL cells in vitro by using biochemical technique. The plastic-adherent monocytes from human peripheral blood were cultured and induced into DC with rhGM-CSF and rhIL-4 using cell culture and separation technique. The cultured DC were harvested and pulsed by HSP70-Id complex. DC morphology was observed under converted phase microscope and its phenotype was characterized by FCM on 8th day as well as their secreting cytokines were measured. Host lymphocytes were stimulated by DC loaded with HSP70-Id complex and co-cultured in the medium containing IL-2. The activation and proliferation of lymphocytes were examined by MTr test, which was also used to assay cytotoxicity of CTL elicited by modified DC to Daudi, K562 and HepG2 tumor cells, and FCM analyzed the changes of T lymphocyte subsets. RESULTS: Mature DCs were obtained successfully, showing typical morphology and phenotypic properties, the expression ratio of cellular surface molecules, CD1a was 20% - 30%, CD83 was more than 72% , both CD86 and HLA-DR over-expressed obviously in the complex-loaded DC group secreting cytokines of Thl type, IL-12 and TNF-alpha. The culturing lymphocytes that were activated by modified DC could more effectively and specifically kill Daudi (71. 24%), but not K562 and HepG2 tumor cells. Results of FCM assay demonstrated that percentage of CD4+ and CD8+ T lymphocytes cocultured with complex-modified DC increased notably to 56.51% and 70.21%, respectively. CD4+ T/ CD8+ T proportion was changed from 1.49 to 0.81. The dose of peptide would be reduced to 1/50 if specific CTL induced by complex-modified DC instead of directly by peptide complex. CONCLUSION: DCs modified by HSP70-Id complex exhibit powerful biological activities, and could induce CTL to specific cytotoxicity against carcinoma cells. It might be produced by cooperation of CD4+ T, CD8+ T lymphocytes and DC. The results also suggested that DC modified by HSP70-Id complex can present antigen and induce CTL with high efficacy and specificity.

Cell Line, Tumor↗

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↗

Structural determinants of quaternary ammonium blockers for batrachotoxin-modified Na+ channels.

Amphipathic quaternary ammonium (QA) compounds are potent blockers of batrachotoxin (BTX)-modified Na+ channels incorporated into planar lipid bilayers. To examine the topology of the QA binding site, we selected two series of QA compounds as structural probes. One series contains two separate hydrophobic moieties but with a common hydrophilic dimethyl QA ion. Most of the QAs within this group bind to BTX-modified Na+ channels with relatively high affinities. For example, benzyldimethyldodecyl ammonium ions, when applied internally, block single, muscle, BTX-modified Na+ channels in bilayers with a one-to-one relationship and display an equilibrium dissociation constant (Kd) of 0.2 microM at +50 mV. Furthermore, the QA dwell times appear to correlate with QA hydrophobic interactions with the channel. These results indicate that there are two large hydrophobic binding domains within the QA binding site. The QAs in the second series contain a hydrophilic head group (trialkylammonium) of variable size but with a common dodecyl hydrophobic tail. Tripropyldodecyl QAs block BTX-modified Na+ channels more effectively (Kd = 0.4 microM at +50 mV) than do trimethyl- and triethyldodecyl QAs, suggesting that the internal Na+ permeation pathway is at least 9 A wide. However, tributyl- and tripentyldodecyl QAs show much lower affinities for BTX-modified Na+ channels at comparable concentrations. These drugs are cut off from binding, probably as a result of the size of their hydrophilic heads (> 10 A), which may be too large to fit in the QA binding site and too bulky to travel freely within the internal permeation pathway. Under whole-cell voltage-clamp conditions, we have further found that BTX-modified Na+ currents in clonal GH3 cells can be blocked by these two series of QA ions, albeit only when the activation gate is open. Closed channels at rest do not bind appreciably with these QA ions. Binding of QA ions is reduced by external Na+ ions in GH3 cells in a manner indicating that external Na+ ions can clear the bound QA ions from the Na+ pore. These results from GH3 cells mirror those obtained with QA blockers in K+ channels of squid axons and suggest that the QA binding domains in BTX-modified Na+ channels and K+ channels may be structurally conserved.

Animals↗

[Clinical experience with modified method of tubal ligation].

OBJECTIVE: To evaluate the clinical results with modified tubal ligation method. METHODS: From 1983 to 1992, 700 cases of modified tubal ligation operation with tubes cut and overlapped were performed in our hospital, and this was compared with 602 cases of Pomeroy's and 502 cases of modified Uchida's method. Patients were followed at 6 months, 2 and 5 years. Pregnancy rates, menstruation disturbances, lower abdominal or back pain, and leucorrhea were observed. RESULTS: Patients with modified tubal ligation method had a pregnancy rate of 0.43%, which was significantly lower than that of Pomeroy's 1.50% (P < 0.05). The modified method group also had few complications. The occurence rate of menorrhage and prolonged bleeding were apparently lower than that of Pomeroy's too (P < 0.01). CONCLUSION: This modified tubal ligation method is more effective and practicable than Pomeroy's and modified Uchida's method.

Adult↗

Effects of immediate modified feeding on infantile gastroenteritis.

BACKGROUND: Standard treatment of infants who are dehydrated as a result of acute gastroenteritis is to administer oral rehydration therapy (ORT). Traditionally, food has been withdrawn for 24-48 h, but there is no conclusive evidence that this is of any real benefit to the patient. Immediate modified feeding, in which an infant on ORT is not starved but administered a limited diet, may have benefits in the treatment of gastroenteritis, especially in children who are nutritionally compromised before they develop the illness. AIM: A pilot study was carried out to investigate the effects of giving infants suffering from acute gastroenteritis a limited modified diet in conjunction with ORT. METHOD: Infants recruited into the study by their general practitioner or by a research doctor in the hospital casualty unit of Bristol Children's Hospital were randomly allocated to receive ORT with or without immediate modified feeding. The duration of diarrhoea, weight change, and incidence of vomiting and lactose intolerance were measured in both treatment groups, and the results were compared. RESULTS: Of the infants studied, 27 received ORT and immediate modified feeding, and 32 ORT alone. The duration of diarrhoea, and incidence of vomiting or lactose intolerance were no greater in the group receiving immediate modified feeding. Patients who received ORT and immediate modified feeding appeared to gain more weight than the infants who were starved for 24-48 h, but this difference was not statistically significant. CONCLUSION: Immediate modified feeding is safe and effective, and may have nutritional advantages over traditional ORT with starvation. A similar but multicentre study using unmodified diet, i.e. child's normal diet, is being carried out by a working group of The European Society of Paediatrics, Gastroenterology and Nutrition (ESPGAN).

Child, Preschool↗

Molecular design of hybrid tumor necrosis factor-alpha III: polyethylene glycol-modified tumor necrosis factor-alpha has markedly enhanced antitumor potency due to longer plasma half-life and higher tumor accumulation.

We have reported that chemical modification of tumor necrosis factor-alpha (TNF-alpha) with polyethylene glycol (PEG) markedly increases its antitumor potency without any adverse side effects. MPEG-TNF-alpha, especially, in which 56% of the lysine amino groups of TNF-alpha are coupled with PEG, exhibits 100-fold more antitumor activity in vivo than native TNF-alpha in the Meth-A murine sarcoma model. In this study, we investigated the pharmacokinetics of PEG-modified TNF-alpha with various molecular sizes to clarify the mechanisms of the enhanced antitumor potency of MPEG-TNF-alpha. The plasma half-lives of modified TNF-alpha increased with increasing molecular size. The decreased plasma clearance of modified TNF-alpha was partially caused by the shielding effect of the proteolytic sites in TNF-alpha by the attached PEG and the decreased transport from blood to various tissues. Almost all native TNF-alpha was uniformly distributed to the kidney and reticuloendothelial system within 1 hr of an intravenous administration, and rapidly disappeared from these tissues at 3 hr. However, very little native TNF-alpha was transported into the tumor. The absolute distributed amount and distribution profile of modified TNF-alpha to tissues other than the tumor were the same as those of native TNF-alpha, whereas the plasma levels of the modified TNF-alpha were higher than plasma levels of the native TNF-alpha. The tumor distribution of modified TNF-alpha was markedly enhanced compared with native TNF-alpha and gradually increased over time. About 9-fold more MPEG-TNF-alpha was distributed to the tumor than native TNF-alpha. Thus, we found that the marked increase in the antitumor potency of PEG-modified TNF-alpha resulted from the enhanced blood residency and tumor accumulation. The antitumor effect of MPEG-TNF-alpha against sarcoma-180 other than Meth-A fibrosarcoma was also about 100 times greater than that of native TNF-alpha when systemically administered. The optimal PEGylation of TNF-alpha facilitated its antitumor potency and MPEG-TNF-alpha may be useful systemic antitumor therapeutic drug.

Animals↗