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Electropharmacologic effects of class I and class III antiarrhythmia drugs on typical atrial flutter: insights into the mechanism of termination.

BACKGROUND: Acute effects of class I and class III antiarrhythmia drugs on the reentrant circuit of typical atrial flutter are not fully studied. Furthermore, the critical electrophysiologic determinants of flutter termination by antiarrhythmia drugs are not clear. METHODS AND RESULTS: The study population consisted of 36 patients (mean age, 53+/-17 years) with clinically documented typical atrial flutter. A 20-pole "halo" catheter was positioned around the tricuspid annulus. Incremental pacing was performed to measure the conduction velocity along the isthmus and lateral wall, and extrastimulation was performed to evaluate atrial refractory period in the baseline state and after intravenous infusion of ibutilide, propafenone, and amiodarone. Efficacy of these drugs in conversion of typical atrial flutter and patterns of termination were also determined. Ibutilide significantly increased the atrial refractory period and decreased conduction velocity in the isthmus at short pacing cycle length. It terminated atrial flutter in 8 (67%) of 12 patients after prolongation of flutter cycle length due to increase (86+/-19%) of conduction time in the isthmus. Propafenone predominantly decreased conduction velocity with use dependency and significantly increased atrial refractory period, but it only converted atrial flutter in 4 (33%) of 12 patients. Amiodarone had fewer effects on atrial refractory period and conduction velocity than did ibutilide and propafenone, and it terminated atrial flutter in only 4 (33%) of 12 patients. Termination of typical atrial flutter was due to failure of wave front propagation through the isthmus, which occurred with cycle length oscillation, abruptly without variability of cycle length, or after premature activation of the reentrant circuit. CONCLUSIONS: Ibutilide, with a unique increase in atrial refractoriness, was more effective in conversion of atrial flutter than were propafenone and amiodarone.

Adult↗

Human leukocyte antigen class I, class II, and tumor necrosis factor-alpha polymorphisms in a healthy elder Mexican Mestizo population.

BACKGROUND: There is strong evidence that an individual's genetic background is an important predisposing factor to longevity. In the present study we analysed the frequency of HLA class I, class II, as well as the TNF-alpha -308 polymorphism that may be related to an increased life span in Mexican Mestizo healthy elders. RESULTS: HLA typing was performed by polymerase chain reaction sequence specific oligonucleotide (PCR SSO) reverse dot blot. The TNF-alpha -308 polymorphism was assessed by PCR restriction fragment length polymorphism. A significant increased frequency of HLA-DRB1*11 was found in elderly women whereas this allele was not present in elderly males. The TNF2 allele was also increased in the elder group when compared to young controls. The frequencies of the remaining alleles tested were not statistically different among groups. CONCLUSION: These data suggest an ethnicity independent tendency of HLA-DRB1*11 in elder females to increase life span and a possible role of the TNF2 allele with the successful remodelling of senescent immune system.

Journal Article↗

Structural classification of plant chitinases: two subclasses in class I and class II chitinases.

For the classification of plant chitinases, phylogenetic relationships were analyzed besides the established classification of domain structure and C-terminal extension sequences. Two genetically different subclasses (high and low molecular weight) were found for the main structure of class I and class II chitinases in their phylogenetic trees. The genetic distance of these subclasses showed that the high molecular weight subclass may be an ancestral molecule.

Amino Acid Sequence↗

Antifungal activity of rye (Secale cereale) seed chitinases: the different binding manner of class I and class II chitinases to the fungal cell walls.

The antifungal activities of rye seed chitinase-a (RSC-a, class I) and -c (RSC-c, class II) were studied in detail using two different bioassays with Trichoderma sp. as well as binding and degradation experiments with the cell walls prepared from its mycelia. RSC-a inhibited more strongly the re-extension of the hyphae, containing mainly mature cells, than RSC-c did. Upon incubation of the fungus with fluorescent chitinases, FITC-labeled RSC-a was found to be located in the hyphal tips, lateral walls, and septa, while FITC-labeled RSC-c was only in the hyphal tip. RSC-a had a greater affinity for the cell walls than RSC-c. RSC-a liberated a larger amount of reducing sugar from the cell walls than RSC-c did. These results inferred that RSC-a first binds to the lateral walls and septa, consisting of the mature cell walls, and degrades mature chitin fiber, while RSC-c binds only to the hyphal tip followed by degradation of only nascent chitin. As a result, RSC-a inhibited fungal growth more effectively than RSC-c. Furthermore, it was suggested that the chitin-binding domain in RSC-a assists the antifungal action of RSC-a by binding to the fungal hypha.

Antifungal Agents↗

Health-related quality of life in patients with class II and class III obesity.

BACKGROUND: Severe obesity may substantially impact quality of life. We estimated the health-related quality of life (HRQoL) in patients with class II and class III obesity, and explored the impact of patient characteristics and co-morbidities on quality of life. METHODS: 110 patients with BMI > or = 35 kg/m2 presenting for evaluation for bariatric surgery were asked to complete the EuroQoL questionnaire. Co-morbidities of the patients were recorded, including coxarthralgia, gonarthralgia, foot problems (pain and arthrosis), diabetes, dyslipidemia, hypertension, infertility, coronary heart disease, low back pain, peptic esophagitis, sleep apnea syndrome, urinary stress incontinence, and venous insufficiency. The determinants of HRQoL on the EQ-VAS score and EQ-5D index (both ranging from 0-100) were analyzed in a univariate and multivariate linear regression model. RESULTS: The mean EQ-5D index (societal perspective) was 76, whereas the mean EQ-VAS (patient perspective) was 66 (P<0.0001). The mean number of comorbidities was 4.9 (range 0-11). Dyslipidemia (68%), low back pain (63%) and venous insufficiency (57%) were the 3 most frequent co-morbidities. However, low back pain (beta= -11.4) and foot problems (beta= -8.5) were significantly associated with a reduction in the EQ-VAS score, whereas low back pain (beta= -8.4) and coronary heart disease (beta= -24.9) were significantly associated with a reduction in the EQ-5D index. CONCLUSION: The number and type of co-morbidities determine HRQoL in patients with severe obesity. Within our study population, a higher BMI, however, was not associated with a lower quality of life.

Adult↗

Teaching Class I and Class II direct composite restorations: results of a survey of dental schools.

The authors surveyed 54 North American dental schools about their teaching programs for posterior composite restorations. Marked variations were noted in the time spent teaching the use of these restorations, their indications and contraindications, and the techniques used for preparing and inserting the restorations. Although the time devoted to teaching placement of posterior composite restorations has increased during the last 10 to 12 years, most recent dental school graduates have minimal clinical experience with Class I and Class II composite restoration.

Bicuspid↗

Novel antiarrhythmic compounds with combined class IB and class III mode of action.

Cardiac arrhythmias represent a major area of cardiovascular research, and for drug therapy, a large choice of antiarrhythmic agents have been available. However, clinical trials with antiarrhythmic drugs have recently indicated that serious side effects may considerably limit the use of various antiarrhythmic agents, in particular, for preventing arrhythmia-related mortality. Amiodarone with its complex mode of action, while exerting a strong and favorable antiarrhythmic action, posseses extracardiac untoward side effects originating from its chemical structure. In this paper, we report on our attempt to develop conceptually new, therapeutically valuable antiarrhythmic compounds, in which Class I/B and Class III features were combined into single molecules bearing no structural resemblance to amiodarone. Synthesis and pharmacological screening of series of N-(phenylalkyl)-N-(phenoxyalkyl)amines led us to discover some new promising compounds with the required dual mode of action. GYKI-16638, selected for further investigation, was also found to possess a remarkable in vivo antiarrhythmic effect, and it is now considered as a safe new antiarrhythmic drug candidate.

Action Potentials↗

An evaluation of the radiopacity of composite restorative materials used in Class I and Class II cavities.

The radiopacity of 28 shades of 18 composite brands, recommended for use in Class I and Class II cavities, and one amalgam were tested in accordance with the instructions in the latest draft standards of ISO for resin-based filling materials. The composition of the inorganic fillers in the materials was analyzed by optical emission spectroscopy. Twelve composites showed radiopacity greater than enamel, for five the radiopacity was lower than that of dentin, and for two materials the radiopacity was between that of enamel and dentin. The optical emission spectroscopy analyses showed a large variety in the composition of the fillers. The elements added to increase radiopacity in the composite materials are barium, strontium, zinc, zirconium, and ytterbium.

Composite Resins↗

Differential decondensation of class I (rat) and class II (mouse) spermatozoa nuclei by physiological concentrations of heparin and glutathione.

The kinetics of sperm nuclear decondensation induced by the action of physiological concentrations of heparin and glutathione was studied by comparing two rodents: the rat, with very stable protamine P1 containing chromatin (class I nuclei), and the mouse, with protamine P1 and protamine P2 (class II nuclei). Sperm suspensions were incubated at different temperatures (37, 40, 43, and 46 degrees C) in media while keeping a constant concentration of either heparin or GSH and increasing concentrations of the other reagent. Spermatozoa nuclei without any treatment incubated for 72 h appear densely condensed. Swelling of mouse spermatozoa nuclei was observed after 30 min of incubation in the presence of efficient concentrations of heparin-GSH. The extent of this time lag was significantly reduced at higher temperatures. This behavior was also observable in the rat, but required time lags of 3-4 h. Electron microscopy observations showed that the pattern of nuclear decondensation was different in both animal species. Mice sperm nuclei initiates its decompaction by the peripheral regions and this behavior remains until late stages of decondensation. On the contrary, rat spermatozoa nuclei decondense initially at the central part of the nuclei while the periphery remains condensed, showing numerous residues of densely packed chromatin. In both cases, the chromatin is organized into "hub-like" nuclear bodies joined by a network of chromatin fibers.

Animals↗

Cancer regression induced by modified CTL therapy is regulated by HLA class II and class I antigens in Japanese patients with advanced cancer.

Autologous cancer-specific bulk CTLs are unlikely to be induced by in vitro CTL generation (ivtCTLG) using peripheral blood mononuclear cells (PBMCs) of cancer patients when autologous cancer cells are used as in vitro stimulators. However, autologous cancer-specific bulk CTLs are frequently activated when allogeneic cancer cells are used as in vitro stimulators, regardless of the type of cancer cell. We have developed a cancer-specific immunotherapy called modified CTL therapy, which involves adoptive immunotherapy of autologous cancer-specific bulk CTLs after active immunization of autologous or allogeneic cancer cells screened as in vitro stimulators according to their ability to induce autologous cancer-specific CTLs (ACS. CTLs). Cancer did not regress in patients in whom ACS.CTLs were not induced by ivtCTLG using the patients' PBMCs in therapy. Cancer regression, albeit temporary, occurred solely in patients under the immunological condition that ACS.CTLs were induced by ivtCTLG using PBMCs through the therapy. The induction of ACS.CTLs by ivtCTLG using patient PBMCs in therapy was related to patients' HLA class II antigens. HLA DR8 was seen more frequently in ACS.CTL-inducible patients than in ACS.CTL-uninducible patients (P=0.051). On the contrary, HLA DQ3 was seen more frequently in ACS.CTL-uninducible patients (P=0.055). On the other hand, the success in therapy, albeit temporary, was related mainly to patients' HLA class I antigens. HLA B61 was seen more frequently in patients whose therapy proved effective than in patients whose therapy proved ineffective (P=0.018). HLA Cw7 was seen more frequently in therapy-ineffective patients (P=0.040).

Adult↗

Application of world class service to world class nursing.

U.S. nursing is in trouble. These numerous and multidimensional troubles include general job dissatisfaction, low morale, a severe nurse shortage, a high turnover rate, and a rapid cost increase. A brief study of the healthcare industry in other industrialized nations revealed that those nations do not face the same problems or at least their problems are not as severe. More specifically, the Japanese nursing industry has no shortage. This article addresses some of the United State's nursing problems and presents some solutions from World Class Service concepts to those problems. The concepts of flexible scheduling, simplification of processes and standardization, on-the-job training, employee involvement, and team building are discussed in the context of World Class Nursing. Finally, the importance of regarding all of the above mentioned concepts as an integral part of healthcare improvement efforts is emphasized.

Economics, Nursing↗

[A study of seat-taking in seminar classes: data analysis of three seminar classes in a women's university].

The purpose of this study was to examine the conditions under which human territoriality (self/other boundary-regulation mechanism) appears in seat-taking behavior. Seat-taking in a social psychology seminar class of twelve students at a women's university was observed during the 1983, 1984 and 1985 academic years by female part-time lecturer (the author herself). At the beginning of each class, the lecturer drew the figure of the students' seating arrangement at a rectangular table, while calling each student's name. Questionnaires were also administered to the students at the end of the observation in the period 1983 and 1985 academic years. The results obtained were: 1) each student was more attached to one seating area and seating side than the others, 2) this fact reflected her seating preference to some extent, 3) no student monopolize the special seats to which she was most attached, 4) extra spaces were left between the lecturer's and the student's seat. The third finding was considered to be due to homogeneity of the student with respect to major, grade and sex and their temporal relationships within the seminar group. Also the fourth result was due to the status difference between the lecturer and the students, which led to the recognition that the seating places were mutually exclusive for both sides of them.

Adult↗

Medical devices; retention of three preamendment class III devices in class III--FDA. Final rule.

The Food and Drug Administration (FDA) is retaining the following three preamendments class III devices in class III: Lung water monitor, powered vaginal muscle stimulator for therapeutic use, and stair-climbing wheelchair. The agency is taking this action because insufficient information exists to determine that special controls would provide reasonable assurance of their safety and effectiveness, and/or these devices present a potential unreasonable risk of illness or injury.

Device Approval↗

Medical devices; reclassification of six cardiovascular preamendments class III devices into class II. Final rule.

The Food and Drug Administration (FDA) is reclassifying six cardiovascular pre amendments devices from class III (pre market approval) into class II (special controls). FDA is also identifying the special controls that the agency believes will reasonably ensure the safety and effectiveness of the devices. This reclassification is being undertaken on the agency's own initiative based on new information under the Federal Food, Drug, and Cosmetic Act (the act), as amended by the Safe Medical Devices Act of 1990 and the Food and Drug Administration Modernization Act of 1997. The agency is also revising the identification of one of the devices subject to this rule to simplify the classification regulation and is correcting a typographical error that was incorporated into the regulations.

Cardiology↗

Medical devices; reclassification of three anesthesiology preamendments class III devices into class II. Final rule.

The Food and Drug Administration (FDA) is reclassifying three anesthesiology preamendments devices from class III (premarket approval) into class II (special controls). FDA is also identifying the special controls that the agency believes will reasonably ensure the safety and effectiveness of the devices. This reclassification is being undertaken on the agency's own initiative based on new information under the Federal Food, Drug, and Cosmetic Act (the act), as amended by the Safe Medical Devices Act of 1990 and the FDA Modernization Act of 1997.

Anesthesiology↗

[Clinical characteristics affecting the need for relining of class 1 and class 2 removable mandibular prostheses].

This study attempts to identify, from a sample of people wearing a class 1 or 2 removable prosthetic device on the lower jaw, the extent of the relining needs for these prostheses and their determining factors. Epidemiological methods were used to solve this problem. The relining needs increase with the amount of time elapsed since the prosthetic device was put in the mouth (p = 0.014). As for the other factors reviewed, i.e. class of device, type of retainers used, and occlusion, the authors have identified trends instead of real risk factors, since the impact of this study was significantly reduced due to the small number of people we were able to recruit. It was not always possible, therefore, to verify the statistical meaning of the associations observed. In clinical practice, the treatment plan should include a periodical evaluation of the relining needs. As it is now impossible to establish the approximate time when a prosthetic device may need relining, patients wearing one should be examined periodically and regularly.

Adult↗

[Major histocompatibility complex class II transactivator (CIITA) hammer- head ribozyme transfer inhibits major histocompatibility complex class II (MHC-II) expression in Jukart cells].

OBJECTIVE: Graft versus host disease (GVHD), a major cause of graft failure in allo-hematopoietic cell transplantation, was associated with the presence of major histocompatibility complex class II (MHCII), also called human leukocyte antigen (HLAII), on the tissues and organs of host. MHCII played a critical role in the induction of immune responses by presenting fragments of allo-antigenic peptides to CD(4)(+) T lymphocytes, then by resulting in CD(8)(+) T lymphocytes activation. Therefore, it was very important for compatibility of MHCII in allo-transplantation. But it was impossible to down-modulate MHCIIexpression directly. There were codominance and multiple allele for MHCII molecules which was owing to their complicated polymorphism, therefore it was difficult to repress every MHCII molecule expression. MHC class II transactivator (CIITA) was the major rate-limiting factor for both constitutive and inducible MHCIIexpression., and with rare exceptions, its expression paralleled that of MHCII transcripts. This study investigated the effect of anti-CIITA hammerhead ribozyme (Rz) on interferon (IFN)-gamma induced MHCII expression in Jukart cell line. METHODS: Three hammerhead Rz specific to 134, 218, 464 sites of CIITA gene were synthesized and named as Rz134, Rz218, Rz464, respectively. Then they were cloned into the EcoRI/BamHI of vector pGEM-7zf(+). CIITA target gene was obtained from Raji cell by RT-PCR, and then inserted also into the pGEM-7zf(+) plasmid. The above recombinant plasmids were screened out by sequence analysis. Hammerhead Rz and their target RNA were transcribed and then mixed up and incubated in vitro. The cleavage products were analyzed by PAGE and silver-staining. Rz464 was selected as the one with the highest activity, and then inserted into the plasmid with internal ribosome entry site-enhanced green fluorescent protein (pIRES2-EGFP), pRz464. Stable transfectants of Jukart cell line with pRz464 (pRz464-J) were tested for classic MHCII (HLA-DR, DP, DQ) induction by recombinant human IFN-gamma. mRNA abundance of CIITA was measured by RT-PCR. RESULTS: When induced with IFN-gamma, the expression of HLA-DR, DP, DQ in pRz464 positive (pRz464+) Jukart cells was 2.7%, 6.4% and 2.1%, respectively, and that in Jukart cells transfected by non-related ribozyme was 10.1%, 57.8% and 5.1%, respectively. Therefore, Rz464 suppressed IFN-gamma-induced up-regulation of HLA-DR, DP and DQ by 73.27%, 88.93% and 58.82%, respectively. Meanwhile, the mRNA content of CIITA was reduced significantly (P < 0.01). CONCLUSION: CIITA hammerhead ribozyme transfer inhibited MHC-II expression in Jukart cells. The above result provided insight into the future application of anti-CIITA hammerhead ribozyme for the antigen-specific tolerance induction and anti-GVHD treatment in the hematopoietic stem cell transplantation.

Cell Line, Tumor↗

Association of HLA class I and class II alleles with psoriasis vulgaris in Turkish population. Influence of type I and II psoriasis.

OBJECTIVE: To investigate the role of human leukocyte antigen (HLA) in susceptibility to psoriasis vulgaris in the Northeast region of Turkey and to contribute to the data related to HLA and psoriasis. METHODS: The study included 72 unrelated psoriatic patients (43 men and 29 women; aged 11-76 years) admitted to the Dermatology Department, University Research Hospital, Erzurum, Turkey between April 2002 and November 2003. We studied the distribution of HLA class I and II antigens in patients with psoriasis: 72 patients were divided into 2 groups according to the onset of psoriasis before age 40 years with family history (type I) and onset after age 40 without family history (type II). The HLA class I and II antigens were analyzed using the PCR-SSP method in 72 patients and in 104 controls. RESULTS: We found an increase in HLA-A*30 and A*68, B*7, B*13, B*57, Cw6, and DRB1*07 antigens in psoriatic patients compared with controls. As we compared type I and type II psoriasis with control group, B*57, Cw6 and DRB1*07 alleles were more significant in patients with type I psoriasis. Our patients with type II psoriasis represented a significant association with the HLA-B*13. CONCLUSION: Our findings along with previous HLA studies on psoriasis vulgaris patients from different racial groups showed that HLA-B*57 and DRB1*07 alleles are associated with the disease.

Adolescent↗