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Biomedical subjects

S Allen

Publications and source records attributed to S Allen.

At least 55 records · Page 3Linked to original sources
PubMed2000

A multifilamented electrode in the middle cardiac vein reduces energy requirements for defibrillation in the pig.

OBJECTIVE: To compare the defibrillation efficacy of a novel lead system placed in the middle cardiac vein with a conventional non-thoracotomy lead system. METHODS: In eight pigs (weighing 35-71 kg), an electrode was advanced transvenously to the right ventricular apex (RV), with the proximal electrode in the superior caval vein (SCV). Middle cardiac vein (MCV) angiography was used to delineate the anatomy before a three electrode system (length 2 x 25 mm + 1 x 50 mm) was positioned in the vein. An active housing (AH) electrode was implanted in the left pectoral region. Ventricular fibrillation was induced and biphasic shocks were delivered by an external defibrillator. The defibrillation threshold was measured and the electrode configurations randomised to: RV-->AH, RV+MCV-->AH, MCV-->AH, and RV-->SCV+AH. RESULTS: For these configurations, mean (SD) defibrillation thresholds were 27.3 (9.6) J, 11.9 (2.9) J, 15.2 (4.3) J, and 21.8 (9.3) J, respectively. Both electrode configurations incorporating the MCV had defibrillation thresholds that were significantly less than those observed with the RV-->AH (p < 0.001) and RV-->SCV+AH (p < 0.05) configurations. Necropsy dissection showed that the MCV drained into the coronary sinus at a location close to its orifice (mean distance = 2.7 (2.2) mm). The MCV bifurcated into two main branches that drained the right and left ventricles, the left branch being the dominant vessel in the majority (6/7) of cases. CONCLUSIONS: Placement of specialised defibrillation electrodes within the middle cardiac vein provides more effective defibrillation than a conventional tight ventricular lead.

Analysis of Variance↗
PubMed2000

Characteristics of HLA class I and class II polymorphisms in Rwandan women.

OBJECTIVE: To define HLA class I and class II polymorphisms in Rwandans. METHODS: PCR-based HLA genotyping techniques were used to resolve variants of HLA-A, B, and C to their 2- or 4-digit allelic specificities, and those of DRB1 and DQB1 to their 4- or 5-digit alleles. RESULTS: Frequencies of 14 A, 8 C, and 14 B specificities and of 13 DRB1 and 8 DQB1 alleles were >/=0.02 in a group of 280 Rwandan women. These major HLA factors produced 6 haplotypes extending across the class I and class II regions: A*01-Cw*04-B* 4501-DRB1*1503-DQB1*0602 (A1-Cw4-B12- DR15 - DQ6), A * 01 - Cw * 04 - B * 4901 -DRB1 * 1302-DQB1*0604 (A1-Cw4-B21-DR13-DQ6), A*30 - Cw*04 - B*15 - DRB1*1101 - DQB1*0301 (A19-Cw4-B15-DR11-DQ7), A*68-Cw*07-B* 4901-DRB1*1302-DQB1*0604(A28-Cw7-B21- DR13 - DQ6), A*30 - Cw*07 - B*5703 - DRB1* 1303-DQB1*0301(A19 - Cw7 - B17 - DR13 - DQ7), and A*74-Cw*07-B*4901-DRB1*1302-DQB1* 0604 (A19-Cw7-B21-DR13-DQ6), respectively. Collectively, these extended haplotypes accounted for about 19% of the total. Other apparent class I-class II haplotypes (e.g., Cw*17-B*42-DRB1*0302-DQB1*0402, Cw*06- B*58-DRB1*1102-DQB1*0301, and Cw*03- B*15-DRB1*03011-DQB1*0201) did not extend to the telomeric HLA-A locus, and other 3-locus class I haplotypes (e.g., A*68-Cw*04-B*15, A*74-Cw*04-B*15, and A*23-Cw*07-B*4901) completely or partially failed to link with any specific class II alleles. DISCUSSION: Frequent recombinations appeared to occur between the three evolutionarily conserved HLA blocks carrying the class I and class II loci. The HLA class I profile seen in Rwandans was not directly comparable with those known in the literature, although the class II profile appeared to resemble those in several African populations. These data provide additional evidence for the extensive genetic diversity in Africans.

Alleles↗
PubMed2000

Treatment of spit tobacco users with transdermal nicotine system and mint snuff.

The purpose of this study was to examine the effects of nicotine patch and mint snuff (a nonnicotine product) on craving, withdrawal symptoms, and treatment outcome. This study involved a 2 x 2 factorial design, with Active Nicotine Versus Placebo Patch as one of the factors and Mint Snuff Versus No Mint Snuff as the other factor. Spit tobacco users (N = 402, n = 100-101 in each condition) were randomly assigned to 1 of the 4 treatment conditions for a period of 10 weeks. Treatment outcome was measured up to 62 weeks. The results showed that the nicotine patch was effective in increasing short-term abstinence over the placebo patch and in reducing craving and withdrawal signs and symptoms from spit tobacco. Although mint snuff was not effective in enhancing treatment outcome, it reduced craving and withdrawal symptoms. No interaction effects were observed. At this time, the use of the nicotine patch and mint snuff should be primarily considered for the reduction of craving and withdrawal symptoms.

Administration, Cutaneous↗
PubMed1999

The influence of epitope availability on atomic-force microscope studies of antigen-antibody interactions.

The ability of the atomic-force microscope (AFM) to detect interaction forces between individual biological molecules has recently been demonstrated. In this study, force measurements have been obtained between AFM probes functionalized with the beta-subunit of human chorionic gonadotrophin (betahCG) and surfaces functionalized with anti-betahCG antibody. A comparison of the obtained results with previous anti-ferritin antibody-binding data identifies differences when the antigen molecule expresses only a single epitope (betahCG), rather than multiple epitopes (ferritin), for the monoclonal antibodies employed. Specifically, the probability of observing probe-sample adhesion is found to be higher when the antigen expresses multiple epitopes. However, the periodic force observed in the adhesive-force distribution, due to the rupture of single antigen-antibody interactions, is found to be larger and more clearly observed for the mono-epitopic system. Hence, these findings indicate the potential of the AFM to distinguish between multivalent and monovalent antibody-antigen interactions, and demonstrate the influence of the number of expressed epitopes upon such binding studies.

Adhesiveness↗
PubMed1999

Typing of Leishmania lipophosphoglycans by electrospray mass spectrometry.

A method has been developed to identify the repeating phosphosaccharide units of Leishmania lipophosphoglycans using electrospray mass-spectrometry (ES-MS). Cone voltage-induced fragmentation of intact lipophosphoglycan was found to be as effective as analysis of mild acid hydrolysates in identifying the degree of modification of the repeating units of lipophosphoglycans derived from Leishmania mexicana and Leishmania major. This finding was exploited in a 'rapid-analysis' method in which a crude organic extract of approximately 2 x 10(9) L. major promastigote cells was loaded onto a reverse-phase cartridge for immediate elution into the mass-spectrometer. Using this approach, it was possible to identify the repeating units by total ion scanning and scanning for parents of the m/z 79 (PO3-) fragment ion. This approach is suitable for quick-typing of lipophosphoglycan repeats and was shown to detect alterations in repeat side chains caused by: (1) culturing L. major promastigotes in the presence of L-fucose; and (2) in vitro metacyclogenesis of L. major promastigotes. It is anticipated that the method will be applicable to small samples of cultured field isolates or genetically-manipulated strains.

Animals↗
PubMed1999

HLA class I homozygosity accelerates disease progression in human immunodeficiency virus type 1 infection.

Polymorphic products of HLA class I genes restrict cytotoxic T lymphocyte responses to the constantly evolving spectrum of HIV-1 antigens. Accordingly, homozygosity at class I loci can reduce the repertoire for such HLA-dependent interactions, leading to accelerated disease progression. To test this hypothesis we studied subjects from two distinct HIV/AIDS cohorts: 140 Dutch homosexual men and 202 Rwandan heterosexual women followed up to 13 years from HIV-1 seroconversion. We performed intermediate- and selective high-resolution molecular typing at HLA class I (A, B, and C) and high-resolution typing at HLA class II DRB1 and DQB1. Homozygosity at the HLA-A or -B locus or both was found at increasingly high frequency among individuals with successively more rapid progression to late-stage HIV-1-related conditions. In the combined cohorts (n = 342) the odds ratio (OR) due to HLA-A or -B antigen homozygosity in rapid versus slow progressors was 3.8 (p = 0.003); for Dutch men alone the OR was 3.5 (p = 0.102), and for Rwandan women the OR was 4.1 (p = 0.009). In contrast, homozygous genotypes at either HLA-C, DRB1, or DQB1 alone, or DRB1-DQB1 haplotypes, did not exert any deleterious effect on HIV-1 disease progression. These findings suggest strongly that diversity in addition to sequence specificity at HLA-A and -B loci can influence the rate of disease progression following HIV-1 infection.

Cohort Studies↗
PubMed1999

Antiphospholipid antibodies, proteins C and S, and coagulation changes in sickle cell disease.

The significance, interactions, and sources of coagulation abnormalities and their relationship to clinical severity and painful episodes in sickle cell disease are not clear. To evaluate this, we have examined various measures of coagulation in 37 patients with sickle cell disease (20 patients with HbSS disease and 17 patients with HbSC disease). Measurements have included isotypes of antiphospholipid antibodies (IgG, IgM, IgA) to specific phospholipids; proteins C (activity, total antigen) and S (activity, total and free antigen); measures of coagulation activation (prothrombin fragment 1.2, thrombin-antithrombin, fibrinopeptide A, d-dimers); indicators of clinical severity; and studies obtained during steady states and painful episodes. Results in HbSS disease showed that antiphospholipid antibodies were increased, with IgG phosphatidylserine showing the highest and most frequently increased levels (37% of patients). Protein C (activity) and protein S (activity, total, free antigen) were decreased (P<.01), and all measures of coagulation activation were increased (P<.001). In HbSC disease, antiphospholipid antibodies were normal, protein C (activity) and protein S (free antigen) were decreased (P<.001), and all measures of coagulation activation were increased (P<.02). A strong correlation was observed in HbSS disease between IgG-PS and d-dimers. Moderate correlations occurred between protein C activity and thrombin-antithrombin and fibrinopeptide A, between protein S activity and prothrombin fragment 1.2 and d-dimers, and between protein C and protein S activity. In HbSC disease, moderate and fewer correlations occurred. Significant differences between HbSS disease and HbSC disease were observed in aPLs, proteins C and S, and measures of coagulation activation. Measurements during steady states and during painful episodes were not significantly different. We conclude that the antiphospholipid antibody IgG-PS may contribute to coagulation activation in HbSS disease and that IgG-PS, protein C, and protein S relate to each other and jointly to measures of coagulation activation. The increased level of IgG-PS in HbSS disease most likely reflects exposure of the procoagulant phosphatidylserine on the surfaces of red cell-shed vesicles and sickle red cells, which would further affect coagulation activation. The significant differences in coagulation measures between HbSS disease and HbSC disease are consistent with differences in clinical severity between the diseases. The development of painful episodes does not appear to be related to the coagulation changes.

Adult↗
PubMed1999

A systematic evaluation of conventional and novel transvenous pathways for defibrillation.

INTRODUCTION: Conventional implantable cardioverter defibrillators employ endocardial (shock) electrodes with a lead located in the right ventricular apex (RV) and a "hot-can" electrode located subcutaneously in the left pectoral region. In the event of a high defibrillation threshold (DFT) a third electrode is frequently employed in the superior vena cava (SVC). We report the comparison of conventional and novel locations of additional electrodes with the RV/Can configuration, in a porcine model. METHOD: In 12 anesthetized pigs (30-45 kg), endocardial defibrillation electrodes were randomized to the following locations: RV/Can, RV/Can + SVC, RV/Can + main pulmonary artery (MPA) and RV/Can + left pulmonary artery wedge position (PAW), RV/Can + high inferior vena cava (HIVC), RV/Can + Low inferior vena cava (LIVC). Ventricular fibrillation (VF) was induced using 60 Hz alternating current. After 10 seconds VF a rectangular biphasic shock was delivered by the ARD9000 (Angeion Corp). The DFT was determined for each configuration using a modified four-reversal binary search. All configurations were compared using a repeated measures analysis of variance (ANOVA) statistical test and the five 3-electrode configurations were compared to the RV/Can position using a Dunnett test. RESULTS: Mean DFTs: RV = 21.5 +/- 4.8 J, SVC = 16.8 +/- 4.7 J (p < 0.05 vs. RV), HIVC = 21.1 +/- 4.7 J (p <. 0.05), LIVC = 19.1 +/- 5.7 J (p <. 0.05 vs. RV), MPA = 16.0 +/- 5.8 J (p < 0.01), PAW = 17.5 +/- 4.6 J (p < 0.05 vs. RV). CONCLUSIONS: Relative to the RV/can configuration the addition of a third electrode in the PA, PAW or SVC significantly reduces the DFT in the pig. The addition of an electrode to the IVC did not significantly reduce the DFT in our model.

Animals↗
PubMed1999

Allelic variants of human beta-chemokine receptor 5 (CCR5) promoter: evolutionary relationships and predictable associations with HIV-1 disease progression.

Variability in the natural history of HIV-1 infection has been repeatedly associated with genetic variants in the beta-chemokine receptor 5 (CCR5) locus. While CCR5 coding sequences have demonstrated relatively limited variation, sequences of its promoter appear polymorphic in all major populations. Our studies revealed five major CCR5 promoter alleles with distributions that differed widely among the four distinct ethnic groups from Kigali, Rwanda and Bronx, New York. In particular, promoter allele P*0103 (G59029-T59353-T59356-A59402-C59653) was largely restricted to black subjects. The promoter allele P*0202 (A59029-C59353-C59356-A59402-T59653) was tightly linked to the slightly less frequent CCR2b-641, a variant of the CCR2b gene, which is about 12.7 kbp upstream from the promoter region. Another closely related promoter allele P*0201 (A59029-C59353-C59356-A59402-C59653) exclusively carried the far less common CCR5-delta 32, a 32-bp deletion in the CCR5 coding sequence 2 kbp downstream from the promoter. The homozygous P*0201/*0201 genotype can be predicted as a risk factor for more rapid disease progression. Among human, chimpanzee, pig-tailed macaque, and sooty mangabey promoter allelic sequences, the apparent ancestral lineage of the promoter sequence (G59029-T59353-C59356-A59402-C59653 = human P*0102) was highly conserved across the primate species analyzed here while P*0201 and P*0202 arose more recently than the other three major alleles. Further effort to establish the mechanism by which CCR chemokine receptor polymorphisms govern the initiation and pathogenesis of primate lentivirus infection apparently requires fully detailed genotypic characterization of the affected populations.

Alleles↗
PubMed1999

Performance on WISC-III and WAIS-R NI vocabulary subtests assessed with event-related brain potentials: an innovative method of assessment.

Assessment of intellectual functions is essential for rehabilitative interventions with traumatic brain injury and stroke patients. However, many of these patients are difficult or impossible to assess because of aphasia and physical disabilities that prevent their performance on traditionally administered tests of mental functioning. We present normative evidence obtained from healthy individuals for the efficacy of a new method of assessing such patients using standardized and validated tests formatted for computer presentation and using direct measures of brain activity (event-related brain potentials, ERP) as the measurable response instead of verbal or motor behavior.

Aphasia↗
PubMed1999

Improved efficacy of anodal biphasic defibrillation shocks following a failed defibrillation attempt.

Although it is generally assumed that defibrillation becomes more difficult when the duration of VF is prolonged, after a failed defibrillation attempt, there is little information on the defibrillation efficacy of multiple shocks delivered at the same energy. The purpose of this study was to systematically examine the efficacy of a second shock delivered at the same or reversed polarity after a failed first shock. Defibrillation was attempted after 10 seconds of VF in 12 pigs (30-56 kg) using biphasic waveforms and a nonthoracotomy lead system. Shock energy was held constant for the first and second shocks at 50%-90% of the DFT. The second shock was delivered 10 seconds after a failed first shock. First and second shock polarity (first phase) was randomized to (+, +), (+, -), (-, -), (-, +). The incidence of successful defibrillation (for all polarities) was 12.3% for first and 49.1% for second shocks (P < 0.0001). Anodal first shocks had a 17.2% incidence of success as opposed to a 7.4% incidence of success with cathodal first shocks (P = 0.001). Anodal second shocks had a 55.5% incidence of success compared to a 42.7% incidence of success with cathodal second shocks (P = 0.008). There was no significant benefit from polarity reversal after a failed first shock (P = 0.29). In conclusion, less energy is required for successful defibrillation by a second shock after a failed first. The optimal configuration for first and second shocks is with the RV as anode. Polarity reversal of a second shock after a failed first does not affect the probability of second shock success.

Animals↗
PubMed1999

Catheter mounted coaxially moveable ablation electrode for the creation of linear transmural endocardial lesions.

INTRODUCTION: Use of a novel ablation catheter for the creation of linear transmural endocardial lesions, which uses a coaxially moving ablation electrode mounted on the terminal portion of a catheter shaft and able to move axially for a distance of up to 4 cm, is reported. METHODS AND RESULTS: The coaxially moving ablation electrode is moved by a sliding mechanism in the catheter handle. The distal portion of the catheter shaft is steerable. Bipolar or unipolar electrograms can be recorded from electrodes on the catheter tip and the coaxially moving ablation. Radiofrequency (RF) current is delivered to the coaxially moving ablation electrode with thermocouple temperature control. This ablation catheter was evaluated in five (30 to 65 kg) anesthetized pigs and introduced via the venous/arterial systems into the right and left atrium (1 lesion) (using the retrograde aortic approach). The catheter was maneuvered to bring the slide range into apposition with atrial endocardium. The coaxially moving ablation electrode was deployed to the terminal portion of the catheter's slide range and then withdrawn in 2-mm steps. RF current was delivered to the coaxially moving ablation electrode at each point (maximum temperature 70 degrees C). Postmortem examination of eight endocardial linear lesions (2.2 to 4.1 cm length) was made 1 to 3 hours after creation. Histopathologic examination confirmed transmural myocyte necrosis along the length of the lesion, that included the trabeculated right atrium. CONCLUSION: We conclude that a catheter using a moveable electrode creates continuous linear transmural lesions and could find clinical application in the therapy of a variety of reentry tachycardia mechanisms.

Animals↗
PubMed1999

Dehydroepiandrosterone replacement in aging humans.

Because so much medical and media attention has been drawn to the alleged benefits of dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS), it is important to evaluate the effects of replacement therapy objectively using double blind, cross-over, randomized research methodology. In this 9-month study, healthy older men (n = 39) received replacement dose DHEA. Lean body mass, blood hematology, chemistry and endocrine values, as well as urological and psychological data were measured. Data showed some mild and temporary, but significant, changes during oral use of 100 mg DHEA for 3 months compared with placebo taken for 3 months. Body composition did not change during the 6 months of treatment, nor did any urological parameters. Concomitant with the endocrine changes, some small but, significant, variations in blood values (blood urea nitrogen, creatinine, uric acid, alanine transaminase, cholesterol, high density lipoprotein, and potassium) were found. After cessation of DHEA and placebo, followed by 3 months of no treatment, all values previously found to be altered returned to entry baseline. Well publicized effects of the drug reported by others, such as a sense of well-being or improved sexual function, were not found in this study.

Activities of Daily Living↗
PubMed1999

Mechanisms of GDF-5 action during skeletal development.

Mutations in GDF-5, a member of the TGF-beta superfamily, result in the autosomal recessive syndromes brachypod (bp) in mice and Hunter-Thompson and Grebe-type chondrodysplasias in humans. These syndromes are all characterised by the shortening of the appendicular skeleton and loss or abnormal development of some joints. To investigate how GDF-5 controls skeletogenesis, we overexpressed GDF-5 during chick limb development using the retrovirus, RCASBP. This resulted in up to a 37.5% increase in length of the skeletal elements, which was predominantly due to an increase in the number of chondrocytes. By injecting virus at different stages of development, we show that GDF-5 can increase both the size of the early cartilage condensation and the later developing skeletal element. Using in vitro micromass cultures as a model system to study the early steps of chondrogenesis, we show that GDF-5 increases chondrogenesis in a dose-dependent manner. We did not detect changes in proliferation. However, cell suspension cultures showed that GDF-5 might act at these stages by increasing cell adhesion, a critical determinant of early chondrogenesis. In contrast, pulse labelling experiments of GDF-5-infected limbs showed that at later stages of skeletal development GDF-5 can increase proliferation of chondrocytes. Thus, here we show two mechanisms of how GDF-5 may control different stages of skeletogenesis. Finally, our data show that levels of GDF-5 expression/activity are important in controlling the size of skeletal elements and provides a possible explanation for the variation in the severity of skeletal defects resulting from mutations in GDF-5.

Amino Acid Sequence↗
PubMed1999

A new cardiothoracic centre: 'how to do it?'.

All cardiac surgical patients, emergency and routine, from the South West peninsula of England had to travel long distances until 19 months ago, a stressful if not dangerous situation. This paper describes the planning, commissioning and start-up of a brand new cardiac surgical facility. The lessons learnt may help similar projects as provision of specialist health care decentralizes.

Cardiac Care Facilities↗