bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rate‐Dependent Block in the Sinus Venosa of the Swine Heart during Transverse Right Atrial Activation: Correlation Between Electrophysiologic and Anatomic Findings
Authors: GONZALEZ MARIO D. , ERGA KNUT S. , RIVERA JAIME , CONTRERAS LEONARDO J. , MLADINICH CHRISTOPHER R. , SCHULTZ JEFF D. , AFONSO VALTINO X. 
Published: February 2005

Introduction: Whether the crista terminalis or the sinus venosa result in rate‐dependent block during transverse activation of the right atrial activation remains unknown. In the present study, right atrial activation at different cycle lengths was studied in the swine heart using high‐resolution noncontact mapping (Endocardial Solutions). The location of the block was tagged and correlated with postmortem anatomical findings. Methods and Results: Eight pigs were studied using noncontact mapping to obtain right atrial geometry and detailed sequence of activation using noncontact endocardial mapping. During sinus rhythm, activation proceeded uninterrupted craniocaudally along the sinus venosa and crista terminalis with similar conduction velocities (1.08 ± 0.17 and 1.17 ± 0.14 m/sec, respectively). Proximal coronary sinus stimulation was used to create transverse activation of the posterior right atrial wall. A rate‐dependent decrease in conduction velocity occurred in the sinus venosa region (0.93 ± 0.21, 0.82 ± 0.14, and 0.52 ± 0.09 m/sec at 500, 400, and 300 ms, respectively; P < 0.05). The line of block verified by isopotential mapping and double potentials was obtained at cycle lengths of 240 ± 30 ms. This line of the block was tagged with radiofrequency current lesions. Postmortem, all lesions were located in the sinus venosa region, 9.8 ± 4.1 mm from the posteromedial edge of the crista terminalis. This region showed abrupt changes in muscle fiber thickness and orientation as well as in collagen content. Conclusions: The sinus venosa and not the crista terminalis results in a rate‐dependent line of block during transverse right atrial activation. The morphologic characteristics of the sinus venosa appear to facilitate block in this region.
Temporal Patterns of Ventricular Tachyarrhythmia Recurrences Follow a Weibull Distribution
Authors: WOOD MARK A. , GUNDERSON BRUCE , XIA AMY , ZHOU XIAOHONG , PADMANABHAN VASANT , ELLENBOGEN KENNETH A. 
Published: February 2005

Introduction: The objective of this study was to test whether the temporal patterns of ventricular tachyarrhythmia recurrences in patients with implantable cardioverter‐defibrillator (ICD) follow a random or a clustered distribution. Methods: Data analysis was conducted using the Medtronic (Minneapolis, MN) Gem DR database of 521 ICD patients. Patients with ≥3 sustained ventricular tachyarrhythmia detections that resulted in shock or antitachycardia pacing therapies were studied. The times between consecutively treated ICD detections for each patient were compared to an exponential model of random recurrences and a Weibull model for clustered recurrences. Results: Seventy‐one patients had ≥ 3VT episodes during follow‐up of 131 ± 86 days. A total of 2347 VT episodes were recorded (33 ± 65 episodes/patient, median 10 episodes/patient). Patient age was 66 ± 13 years, 78% male, 83% coronary artery disease, ejection fraction 31 ± 11%, and 63% were taking antiarrhythmic drugs. By the Kolmogorov‐Smirnov goodness‐of‐fit test, 38 of 71 patients (53.5%) showed that the pattern of detections differed from an exponential model (P < 0.01 for each patient and the proportion of patients was similar to chance at P = 0.65). In contrast, only 11 out of 71 patients (15.5%) showed that the pattern differed from the Weibull model (P < 0.01 for each patient). The proportion of patients fitting the Weibull model was significantly greater than chance and was greater that the proportion fitting the exponential model (both P < 0.001). The time interval between consecutive detections was less than 1 hour for 78% of all 2347 detections. The proportion of all 521 patients with ≥2, ≥3, ≥ 4, ≥6, ≥8, and ≥10 ICD detections in a 24‐hour period was 10.5%, 9.5%, 8.1%, 7.0%, 6.3%, and 5.2%, respectively. Conclusion: In most patients with ≥3 ICD detections, the recurrence pattern of treated ventricular tachyarrhythmia detections are clustered and can be described by a Weibull distribution. The proportion of patients with multiple detections in a 24‐hour period declines in a linear fashion as the number of events in 24 hours increases from 2 to 10 events.
Dissociation of Membrane Potential and Intracellular Calcium during Ventricular Fibrillation
Authors: WU SUHUA , WEISS JAMES N. , CHOU CHUNG‐CHUAN , ATTIN MINA , HAYASHI HIDEKI , LIN SHIEN‐FONG 
Published: February 2005

Introduction: The cardiac action potential (AP) and the intracellular Ca transient (CaT) are closely associated under normal physiological conditions, but not during ventricular fibrillation (VF). The purpose of this study was to determine whether this dissociation is directly related to the fast activation rate during VF. Methods and Results: We optically mapped AP and CaT simultaneously in nine isolated rabbit hearts. Pinacidil, a KATP channel opener, was used to shorten the action potential duration (APD) in order to capture tissue at fast pacing rates or to induce ventricular tachycardia (VT) comparable to VF activation rates. Mutual information (MI) was used to calculate the degree of AP and CaT coupling. Pinacidil (40 μM) infusion significantly shortened APD. The CL of VF without pinacidil averaged 77 ± 13 ms, whereas the shortest CL achieved during VT under pinacidil infusion was 76 ms. MIs during fast pacing (1.13 ± 0.15 bits) and fast VT (0.88 ± 0.18 bits) were higher than those during baseline VF (0.39 ± 0.11 bits), VF with pinacidil infusion (0.21 ± 0.07 bits) and VF after pinacidil washout (0.36 ± 0.15 bits). MIs during fast pacing or fast VT were higher than that of VFs at comparable dominant frequencies. Conclusions: CaT is closely associated with the AP during fast pacing and fast VT, but not during VF. The reduced MI during VF is not secondary to the fast rate of activation.
Genetic Predisposition to Latex Allergy
Authors: Brown Robert H. , Hamilton Robert G. , Mintz Margaret , Jedlicka Anne E. , Scott Alan L. , Kleeberger Steven R. 
Published: February 2005

Background
Occupational exposure of healthcare workers to natural rubber latex has led to sensitization and potentially life-threatening anaphylaxis. Although environmental exposure to natural rubber latex products is necessary for sensitization, it is not sufficient. A number of genetic factors also seem to contribute to the latex sensitization; however, the multigenic nature of the allergic phenotype has made the identification of susceptibility genes difficult. The current study tests the hypothesis that known functional polymorphisms in genes encoding interleukin 4, interleukin 13, and interleukin 18 occur in a higher frequency in healthcare workers with natural rubber latex allergy.

Methods
Four hundred thirty-two healthcare workers with occupational exposure to natural rubber latex were screened using a clinical history questionnaire and latex-specific immunoglobulin E serology. Genomic DNA was extracted from peripheral blood lymphocytes and analyzed for single-nucleotide polymorphisms in candidate genes of interest. Data from cases and controls were analyzed by nominal logistic regression, with P < 0.05 considered significant.

Results
The latex allergy phenotype was significantly associated with promoter polymorphisms in IL13 -1055 (P = 0.02), IL18 -607 (P = 0.02), and IL18 -656 (P = 0.02) compared with nonatopic controls.

Conclusions
The significant association of IL13 and IL18 promoter polymorphisms with latex allergy suggests a potential location for genetic control in the induction of latex allergy in individuals and extends the understanding of the genetic basis for the induction of immediate-type hypersensitivity in healthcare workers occupationally exposed to natural rubber latex.
Genotyping the Butyrylcholinesterase in Patients with Prolonged Neuromuscular Block after Succinylcholine
Authors: Levano Soledad , Ginz Hans , Siegemund Martin , Filipovic Miodrag , Voronkov Evgueni , Urwyler Albert , Girard Thierry 
Published: February 2005

Background
Succinylcholine remains the standard neuromuscular blocking drug for tracheal intubation in emergency situations. The short duration of action is due to its rapid hydrolytic degradation by butyrylcholinesterase (plasmacholinesterase). Multiple variants of this enzyme are known (A, F, S, H, J, K variants) with different effects on enzyme activity. This study was undertaken to evaluate the use of molecular genetic methods in patients with clinically prolonged neuromuscular block.

Methods
Nine patients with a neuromuscular block of 14 min to 5 h were selected. All four exons of the butyrylcholinesterase were amplified by polymerase chain reaction and analyzed by automated sequencing. Molecular genetic results were compared with clinical relaxation time and with biochemical test results (total butyrylcholinesterase activity, dibucaine and fluoride inhibition).

Results
Seven of nine patients were mutation carriers. Five of these had more than one mutation. The A and K variants were the most frequent variations. Three of four patients who were homozygous for the A variant were also carriers of the K allele. The authors identified one novel mutation (G1294T) introducing a stop codon at amino acid position 432. The duration of neuromuscular block was substantially different between patients with identical butyrylcholinesterase genotypes.

Conclusions
Variations in the genetic sequence of butyrylcholinesterase are frequent in patients with prolonged duration of action of succinylcholine. Direct sequencing of the whole butyrylcholinesterase gene is an appropriate method for genotyping and, accordingly, should be used in future clinical studies with drugs metabolized by this enzyme (e.g., succinylcholine, mivacurium).
Effect of α2B-Adrenoceptor Polymorphism on Peripheral Vasoconstriction in Healthy Volunteers
Authors: Talke Pekka , Stapelfeldt Claudia , Lobo Errol , Brown Ronald , Scheinin Mika , Snapir Amir 
Published: February 2005

Background
Alpha-2B adrenoceptor is the vasoconstrictive subtype in the mouse. Human alpha2B-AR deletion (D) allele has been associated with loss of short-term agonist-promoted receptor desensitization, which may lead to increased vasoconstriction on alpha2 activation. The goal of this study was to test the hypothesis that alpha2B-adrenoceptor activation induces enhanced vasoconstriction in carriers of the DD genotype, compared with carriers of the insertion/insertion (II) genotype.

Methods
The authors administered increasing doses of dexmedetomidine (targeting plasma concentrations of 0.15, 0.3, 0.6, and 1.2 ng/ml) to 16 healthy young volunteers (8 carrying the alpha2B DD genotype, 8 carrying the II genotype) in whom sympatholytic effects of the drug were attenuated by general anesthesia. Measurements were made of finger blood volume (an indicator of vasoconstriction) by photoplethysmographic determination of light transmitted through a finger, finger blood flow by venous occlusion plethysmography, and hemodynamic variables.

Results
All concentration of dexmedetomidine increased light transmitted through the finger (vasoconstriction) and systolic blood pressure and decreased heart rate in both groups (P < 0.001 for all). Dexmedetomidine reduced finger arterial inflow only in the DD group (P < 0.001). Dexmedetomidine had no effect on finger venous outflow or venous capacitance. There were no significant differences between the II and DD groups in any of the variables.

Conclusions
The results of this study confirm the alpha2 agonist induced vasomotor and hemodynamic effects in peripheral vasculature. However, the results do not support the hypothesis that alpha2B-adrenoceptor polymorphism has an effect on peripheral vasoconstriction in humans.
Pharmacogenetic Determinants of Human Liver Microsomal Alfentanil Metabolism and the Role of Cytochrome P450 3A5
Authors: Klees Theresa Mariero , Sheffels Pamela , Thummel Kenneth E. , Kharasch Evan D. 
Published: February 2005

Background
There is considerable unexplained interindividual variability in the clearance of alfentanil. Alfentanil undergoes extensive metabolism by cytochrome P4503A4 (CYP3A4). CYP3A5 is structurally similar to CYP3A4 and metabolizes most CYP3A4 substrates but is polymorphically expressed. Livers with the CYP3A5*1 allele contain higher amounts of the native CYP3A5 protein than livers homozygous for the mutant CYP3A5*3 allele. This investigation tested the hypothesis that alfentanil is a substrate for CYP3A5 and that CYP3A5 pharmacogenetic variability influences human liver alfentanil metabolism.

Methods
Alfentanil metabolism to noralfentanil and N-phenylpropionamide was determined in microsomes from two groups of human livers, characterized for CYP3A4 and CYP3A5 protein content: low CYP3A5 (2.0-5.2% of total CYP3A, n = 10) and high CYP3A5 (46-76% of total CYP3A, n = 10). Mean CYP3A4 content was the same in both groups. The effects of the CYP3A inhibitors troleandomycin and ketoconazole, the latter being more potent toward CYP3A4, on alfentanil metabolism were also determined.

Results
In the low versus high CYP3A5 livers, respectively, noralfentanil formation was 77 +/- 31 versus 255 +/- 170 pmol . min . mg, N-phenylpropionamide formation was 8.0 +/- 3.1 versus 20.5 +/- 14.0 pmol . min . mg, and the metabolite ratio was 9.5 +/- 0.4 versus 12.7 +/- 1.4 (P < 0.05 for all). There was a poor correlation between alfentanil metabolism and CYP3A4 content but an excellent correlation when CYP3A5 (i.e., total CYP3A content) was considered (r = 0.81, P < 0.0001). Troleandomycin inhibited alfentanil metabolism similarly in the low and high CYP3A5 livers; ketoconazole inhibition was less in the high CYP3A5 livers.

Conclusion
In microsomes from human livers expressing the CYP3A5*1 allele and containing higher amounts of CYP3A5 protein, compared with those with the CYP3A5*3 allele and little CYP3A5, there was greater alfentanil metabolism, metabolite ratios more closely resembled those for expressed CYP3A5, and inhibitors with differing CYP3A4 and CYP3A5 selectivities had effects resembling those for expressed CYP3A5. Therefore, alfentanil is metabolized by human liver microsomal CYP3A5 in addition to CYP3A4, and pharmacogenetic variability in CYP3A5 expression significantly influences human liver alfentanil metabolism in vitro. Further investigation is warranted to assess whether the CYP3A5 polymorphism is a factor in the interindividual variability of alfentanil metabolism and clearance in vivo.
Facilitation of Serotonergic Activity and Amnesia in Rats Caused by Intravenous Anesthetics
Authors: Semba Kazunori , Adachi Naoto , Arai Tatsuru 
Published: February 2005

Background
Midazolam and propofol often provoke retrograde amnesia after recovery from anesthesia in humans. Because an increase in central serotonergic activity impairs learning and memory, the authors examined the relation between changes in the serotonergic activity caused by intravenous anesthetics and memory.

Methods
Changes in extracellular concentrations of monoamines and their metabolites were investigated in rat striatum by a microdialysis procedure, and the effects of intraperitoneal injections of midazolam (5 mg/kg), propofol (60 mg/kg), and pentobarbital (15 mg/kg) were then examined. To evaluate the behavioral alteration with these agents, the authors used a step-through passive avoidance test.

Results
Midazolam and propofol slightly increased the extracellular concentration of 5-hydroxytryptamine in the striatum, although pentobarbital did not produce any changes. Midazolam and propofol increased the extracellular concentration of 5-hydroxyindoleacetic acid, a metabolite of 5-hydroxytryptamine, with the peak values each 138% and 138% of that in saline-injected animals, respectively. However, pentobarbital decreased the 5-hydroxyindoleacetic acid concentration to 61% of that in the saline group. Administration of midazolam or propofol immediately after the completing the passive avoidance learning reduced step-through latencies after 24 h, although pentobarbital-injected animals maintained a consistent performance. The effects of midazolam and propofol on step-through latencies were completely antagonized by intracerebroventricular administration of spiroxatrine (5 microg), a 5-hydroxytryptamine 1A antagonist, 30 min before training.

Conclusions
Midazolam and propofol increased central serotonergic activity and provoked retrograde amnesia. Because amnesia was completely diminished by a 5-hydroxytryptamine antagonist, facilitation of the serotonergic system may be involved in retrograde amnesia caused by these agents.
Comparison of the Different Approaches to Saphenous Nerve Block
Authors: Benzon Honorio T. , Sharma Sanjay , Calimaran Arthur 
Published: February 2005

Background
The authors compared the efficacy of the different approaches to saphenous nerve block.

Methods
The following approaches to saphenous nerve block were compared in 10 volunteers: perifemoral, transsartorial, block at the medial femoral condyle, below-the-knee field block, and blockade at the level of the medial malleolus. Each volunteer underwent all five blocks, and the interval between blocks was 3-7 days. The sequence of injection was randomized by Latin square design. Sensory blockade at the medial aspects of the leg and foot and the strength of the anterior thigh muscles were noted.

Results
The transsartorial, perifemoral, and below-the-knee field block approaches were more effective than block at the medial femoral condyle in providing sensory anesthesia to the medial aspect of the leg. The transsartorial approach was more effective than block at the medial femoral condyle and below-the-knee field block in providing sensory anesthesia to the medial aspect of the foot. Compared with the perifemoral approach, the transsartorial approach did not cause weakness of the hip flexors and the knee extensors. In volunteers with partial numbness in the medial aspect of the foot, supplemental block of the medial dorsal cutaneous branch of the superficial peroneal nerve resulted in complete sensory blockade.

Conclusions
Sensory blockade in the medial aspects of the leg and foot is best achieved with the transsartorial approach. In some subjects, supplementary block of the medial dorsal cutaneous branch of the superficial peroneal nerve may have to be performed to assure complete numbness of the medial aspect of the foot.
Normal labor associated with changes in uterine heparan sulfate proteoglycan expression and localization
Authors: Hjelm Cluff Ann , Malmström Anders , Tingåker Berith , David Guido , Ekman‐Ordeberg Gunvor 
Published: February 2005

Hypothesis:  Proteoglycans are well‐known modulators of intercellular communication and signaling. Remodeling of the proteoglycans in the human uterus occurs throughout pregnancy, and during labor. We therefore hypothesize that heparan sulfate proteoglycans (HSPGs) play an important role in establishing normal labor. In this study HSPGs were characterized and localized in human uterine tissue.Methods:  Uterine biopsies were obtained from four nonpregnant women, four women during elective cesarean section and four during emergency cesarean section. The biopsies were extracted using 4 m guanidinium hydrochloride (GuHCL). HSPGs were then purified by repeated ion‐exchange chromatography on dehydroepiandrosterone (DEAE)‐cellulose after digestion with chondroitinase ABC and finally precipitated with Alcian blue. HSPGs were identified by agarose gel electrophoresis and Western blotting. Controlled degradation of the heparan sulfate (HS) side‐chains was performed using heparitinase or deglycosylation with trifluoromethanesulfonic acid (TFMS). The resulting core proteins were separated by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE) and visualized by Coomassie staining. HSPGs were localized in uterine tissue by immunohistochemistry.Results:  SDS–PAGE after deglycosylation indicated the presence of multiple distinct core proteins tentatively identified as syndecans 1–4 and glypican 1. Western blots confirmed the presence of these proteoglycans and also perlecan. Immunohistochemistry revealed that the HSPGs were localized mainly in the smooth muscle with few in the extracellular matrix (ECM). Syndecan 3, the dominant proteoglycan, showed the most pronounced changes during pregnancy and labor.Conclusion:  For the first time several heparan sulfate proteoglycans have been identified and localized in the human uterus and shown to vary in expression during pregnancy and labor. Syndecan 3 had the most outstanding features in this respect.
Reduction in hospitalized women with pelvic inflammatory disease in Oslo over the past decade
Authors: Sørbye Ingvil Krarup , Jerve Fridtjof , Staff Anne Cathrine 
Published: February 2005

Background.  A tuboovarian abscess (TOA) is a common complication of pelvic inflammatory disease (PID), occurring world‐wide in 15–30% of women with PID. The aim of the study was to identify changes during the last 10 years in the number of women hospitalized with PID in Oslo, as well as a change regarding the frequencies of the subdiagnoses salpingitis and tuboovarian abscess.Methods.  We performed a review of computerized diagnosis lists and manual check of the medical records of women hospitalized with PID in Oslo. The years 1990–92 and 2000–02 were included, resulting in information from two time periods 10 years apart. Cases were registered as salpingitis, oophoritis or tuboovarian abscess. Medical and demographic variables from the medical records of women diagnosed during 4 out of the 6 years were described in detail.Results.  We identified 523 women with the diagnosis of PID hospitalized during 1990–92 and 2000–02. There was a 35% reduction in hospitalized cases of salpingitis over the period of 10 years, but the number of cases of tuboovarian abscesses among women admitted for PID remained unchanged from 1990–92 to 2000‐02. We found low frequencies of Chlamydia trachomatis and Neisseria gonorrhoea infections, although documented bacteriological sampling was insufficient.Conclusions.  Fewer patients were hospitalized in Oslo for PID during the time period of 2000–02 compared with 10 years earlier, but a higher percentage of patients had developed TOA compared with the first time period (43% compared with 26%, p = 0.013), indicating a changing clinical panorama of PID.