Biomedical subjects

Mark Wood

Publications and source records attributed to Mark Wood.

10 recordsLinked to original sources

PubMed2006

Nonexcitatory, cardiac contractility modulation electrical impulses: feasibility study for advanced heart failure in patients with normal QRS duration.

BACKGROUND: Cardiac contractility modulation signals are associated with acutely improved hemodynamics, but chronic clinical impact is not defined. OBJECTIVES: The purpose of this randomized, double-blind, pilot study was to determine the feasibility of safely and effectively delivering cardiac contractility modulation signals in patients with heart failure. METHODS: Forty-nine subjects with ejection fraction <35%, normal QRS duration (105 +/- 15 ms), and New York Heart Association (NYHA) class III or IV heart failure despite medical therapy received a cardiac contractility modulation pulse generator. Patients were randomized to have their devices programmed to deliver cardiac contractility modulation signals (n = 25, treatment group) or to remain off (n = 24, control group) for 6 months. Evaluations included NYHA class, 6-minute walk, cardiopulmonary stress test, Minnesota Living with Heart Failure Questionnaire, and Holter monitoring. RESULTS: Although most baseline features were balanced between groups, ejection fraction (31.4% +/- 7.4% vs 24.9% +/- 6.5%, P = .003), end-diastolic dimension (52.1 +/- 21.4 mm vs 62.5 +/- 6.2 mm, P = .01), peak VO(2) (16.0 +/- 2.9 mL O(2)/kg/min vs 14.3 +/- 2.8 mL O(2)/kg/min, P = .02), and anaerobic threshold (12.3 +/- 2.5 mL O(2)/kg/min vs 10.6 +/- 2.4 mL O(2)/kg/min, P = .01) were worse in the treatment group than in the control group. Nevertheless, one death occurred in the control group, and more patients in the treatment group were free of hospitalization for any cause at 6 months (84% vs 62%). No change in ectopy was observed. Compared with baseline, 6-minute walk (13.4 m), peak VO(2) (0.2 mL O(2)/kg/min), and anaerobic threshold (0.8 mL O(2)/kg/min) increased more in the treatment group than in control. None of these differences were statistically significant (small sample size). NYHA and Minnesota Living with Heart Failure Questionnaire changed similarly in the two groups. CONCLUSION: Despite a sicker population in the treatment group, no specific safety concerns emerged with chronic cardiac contractility modulation signal administration. Further study is required to definitively define the safety and efficacy of cardiac contractility modulation signals.

Aged↗

PubMed2006

Dual-chamber versus single-chamber detection enhancements for implantable defibrillator rhythm diagnosis: the detect supraventricular tachycardia study.

BACKGROUND: Delivery of inappropriate shocks caused by misdetection of supraventricular tachycardia (SVT) remains a substantial complication of implanted cardioverter/defibrillator (ICD) therapy. Whether use of optimally programmed dual-chamber ICDs lowers this risk compared with that in single-chamber ICDs is not clear. METHODS AND RESULTS: Subjects with a clinical indication for ICD (n=400) at 27 participating centers received dual-chamber ICDs and were randomly assigned to strictly defined optimal single- or dual-chamber detection in a single-blind manner. Programming minimized ventricular pacing. The primary end point was the proportion of SVT episodes inappropriately detected from the time of programming until crossover or end of study. On a per-episode basis, 42% of the episodes in the single-chamber arm and 69% of the episodes in the dual-chamber arm were due to SVT. Mortality (3.5% in both groups) and early study withdrawal (14% single-chamber, 11% dual-chamber) were similar in both groups. The rate of inappropriate detection of SVT was 39.5% in the single-chamber detection arm compared with 30.9% in the dual-chamber arm. The odds of inappropriate detection were decreased by almost half with the use of the dual-chamber detection enhancements (odds ratio, 0.53; 95% confidence interval, 0.30 to 0.94; P=0.03). CONCLUSIONS: Dual-chamber ICDs, programmed to optimize detection enhancements and to minimize ventricular pacing, significantly decrease inappropriate detection.

Aged↗

PubMed2006

Analysis of tumor-associated stromal cells using SCID GFP transgenic mice: contribution of local and bone marrow-derived host cells.

The green fluorescence protein (GFP) from the UBI-GFP/BL6 transgenic line was bred into C57BL/6J-scid and C.B-17-scid mice for investigating host-tumor cell interactions. These mice express high levels of GFP under the control of the ubiquitin promoter in virtually all cells examined. In tumor tissue generated by implanting tumor cells in the GFP transgenic SCID mice, the tumor cells and tumor-associated murine host cells were clearly distinguished by GFP expression. A population of cells expressing the endothelial cell marker VEGFR-2/Flk-1, and the progenitor markers c-Kit and Sca-1, were incorporated into tumor tissue. The majority of the Flk-1-positive cells were hematopoietic-derived cells that coexpressed CD45. To investigate the contribution of bone marrow-derived cells to the formation of tumor vessels and stroma, tumor cells were implanted in nontransgenic SCID mice that received a bone marrow transplant from GFP-expressing SCID mice. Although GFP-positive cells were readily detected by histology in tumors taken from bone marrow transplanted animals, they were spatially isolated and lacked organization. In contrast, if tumors were implanted in nontransgenic SCID mice adjacent to a patch of transplanted GFP-expressing skin, these tumors recruited GFP-positive cells that organized into tumor vessels. The results demonstrate that hematopoietic-derived cells, including Flk-1+/CD45+ cells, readily colonized the tumor stroma but were minimally incorporated in the tumor vasculature. The majority of the tumor vessels were instead recruited from tissue adjacent to the tumor. The expression of Flk-1 on nonendothelial, tumor-associated host cells raises the possibility that VEGF antagonists, such as Avastin, could inhibit tumor growth by a mechanism involving hematopoietic-derived CD45+/Flk-1+ cells, in addition to direct suppression of endothelial cell function.

Animals↗

PubMed2006

Mucous membrane pemphigoid with fatal bronchial involvement in a seventeen-year-old girl.

PURPOSE: This study was designed to report a case of biopsy-proven mucous membrane pemphigoid with severe bronchial involvement in a young woman. METHODS: Case report of a 17-year-old girl who presented with worsening dyspnea, skin rash, and bilateral ocular injection, symblepharon, and fornix foreshortening. Conjunctival, skin, and bronchial biopsies were performed along with imaging and serological tests in an effort to establish a diagnosis for this unusual constellation of findings. The surprising occurrence of a cerebrovascular accident during her hospitalization also prompted a search for a concurrent coagulation disorder. RESULTS: Immunofluorescence studies of conjunctival, skin, and bronchial tissue specimens revealed deposition of multiple antibody classes at the basement membrane zone. The patient also possessed circulating basement membrane zone antibodies in her serum and a significant titer of antiphospholipid antibodies. She underwent dilation and stent placement for subglottic tracheal and left bronchial stenosis and was treated with immunosuppressive agents. After a favorable initial response, the patient experienced progressive bronchial stenosis and respiratory compromise, culminating in her death from bronchospasm and cardiopulmonary arrest. CONCLUSION: To our knowledge, this is the first report of mucous membrane pemphigoid involving the lower airways that was confirmed by immunofluorescence analysis. It highlights the potentially lethal, systemic nature of mucous membrane pemphigoid and underscores the need to question patients about symptoms of respiratory dysfunction.

Adolescent↗

PubMed2005

X-linked dominant growth suppression of transplanted tumors in C57BL/6J-scid mice.

Tumor susceptibility, angiogenesis, and immune response differ between mouse strains. We, therefore, examined the growth rates of tumor xenografts in three genetically isolated strains of severe combined immunodeficient mice (C.B-17, C57BL/6J, and C3H). Tumors grew at significantly reduced rates in the C57BL/6J-scid strain. Engrafting bone marrow from the C57BL/6J-scid strain onto C.B-17-scid mice did not transfer the slow-growing tumor phenotype to the recipient mice; this counters the supposition that the slow-growing tumor phenotype is caused by a greater immune response to the xenograft in the C57BL/6J-scid strain. To establish the inheritance pattern of the slow-growing tumor phenotype, we reciprocally crossed C.B-17-scid mice and C57BL/6J-scid mice. Tumor growth was suppressed in all of the F1 progeny except the male mice derived from the cross between C.B-17-scid female and C57BL/6J-scid male mice. The F1 male mice that received the X chromosome from the C.B-17 strain displayed a fast-growing tumor phenotype. These results confirm that there are significant strain differences in capacity to support the growth of tumor xenografts. In addition, these results reveal the existence of a dominant allele involved in host suppression of tumor growth on the X chromosome of C57BL/6J mice.

Alleles↗

PubMed2005

Comparison of intraosseous and infiltration injections for venous lidocaine blood concentrations and heart rate changes after injection of 2% lidocaine with 1:100,000 epinephrine.

The purpose of this prospective, randomized study was to compare the venous blood levels of lidocaine and heart rate changes after intraosseous and infiltration injections of 1.8 ml of 2% lidocaine with 1:100,000 epinephrine. Using a crossover design, 20 subjects randomly received an intraosseous and infiltration injection at two separate appointments. The heart rate was measured using a pulse oximeter. Venous blood samples were collected before the injections and at 2, 5, 10, 15, 20, 25, 30, 45, and 60 min after the injections. The blinded plasma samples were analyzed for lidocaine concentrations using high-performance liquid chromatography (HPLC). The intraosseous injection resulted in a statistically significant increase in heart rate, when compared to the infiltration injection, during solution deposition and for 2 min after the injection. The plasma levels of lidocaine were not statistically different for maxillary anterior intraosseous and infiltration injections when using 1.8 ml of 2% lidocaine with 1:100,000 epinephrine.

Adult↗

PubMed2005

Audit of trabeculectomy at a tertiary referral hospital in East Africa.

AIM: To audit medium-term results of trabeculectomy at a tertiary referral unit in east Africa. METHODS: A retrospective review of the files of all patients who underwent trabeculectomy surgery at our hospital during the year 2001. RESULTS: One hundred fifty-seven patients were included. Mean age was 61 years (SD = 12). Thirty-one patients (20%) were women; 120 of 145 (83%) eyes had cup/disc ratios of 0.8 or greater preoperatively. Intraoperative 5-fluorouracil (5FU) was used in 57 cases (36%). Mean follow-up was 8 months (0-28, SD = 7). Mean intraocular pressures (IOP) was 25 mm Hg (6-70, SD = 10) preoperatively, 11 mm Hg (0-32, SD = 5) at 2 weeks postoperatively, and 13 mm Hg (0-42, SD = 6) at latest follow-up. One hundred fifteen patients (73%) had intraocular pressure of 15 mm Hg or less at latest follow-up and 141 (90%) had intraocular pressure of 21 mm Hg or less. Twenty (13%) had restarted antiglaucoma medication during the follow-up period. Thirty-seven of 148 (25%) lost 2 lines of Snellen acuity or equivalent between preoperative measurement and latest follow-up. Early postoperative complications (usually leaking bleb or shallow anterior chamber with hypotony) occurred in 18 patients (12%) and this was associated with postoperative loss of 2 or more lines of Snellen acuity (OR = 1.11 95% CI 1.02-1.22, P= 0.02). Patients having had 5FU had lower (t = 3.11, P= 0.02) mean intraocular pressure at 2-month follow-up (12 mm Hg, SD = 5) than those who did not receive it (16 mm Hg, SD = 6) but there was no significant difference at later follow-ups. Men (mean 14 mm Hg, SD = 6) had higher (t = 2.71, P= 0.01) intraocular pressures at latest follow-up than women (mean 11 mm Hg, SD = 3). CONCLUSIONS: The results of surgery compare well with other reported series. 5FU did not demonstrate significant benefit in terms of intraocular pressure lowering beyond 2 months postoperatively. Early postoperative hypotony should be avoided. The gender difference in intraocular pressure results has not previously been reported and deserves further investigation.

Adult↗

PubMed2005

Transvenous catheter cryoablation for treatment of atrial fibrillation: results of a feasibility study.

Pulmonary vein (PV) isolation using radiofrequency (RF) ablation can induce PV stenosis. Cryoablation may offer a safer alternative energy source for PV isolation. PV isolation with cryoablation was attempted in 31 patients with paroxysmal atrial fibrillation (AF). Event monitors were used to measure the AF episode burden. Serial spiral CT scans were obtained to monitor PV stenosis pre- and postcryoablation. Cryoablation was immediately successful for PV isolation in 29 of 31 patients (94%), with 5.9 +/- 1.2 months of follow-up. Additional RF ablation was performed for AF recurrences in seven patients. The remaining 22 patients with a single cryoablation procedure demonstrated a time-dependent, long-term reduction in the frequency of AF episodes. At 6 months of follow-up, 18 of 22 of cryo-treated only patients (82%) were free of symptomatic AF episodes, and antiarrhythmic drugs were discontinued in 12 of 22 patients. Serial spiral CT scans demonstrated no change in the cryo-treated PV ostial diameter. PV cryoablation was effective to control paroxysmal AF in most patients. Early recurrences of AF postcryoablation were common, though tended to resolve within 6 months postablation, consistent with a process of reverse atrial remodeling. Cryoablation of the PVs did not cause PV stenosis or other serious adverse events.

Adult↗

PubMedDate not supplied

Gender and its effect in cardiovascular pharmacotherapeutics: recent considerations.

Gender differences in drug pharmacokinetics and pharmacodynamics have been recognized for some time. This issue has generally been ignored in clinical practice, despite there being ample evidence to suggest that gender can influence multiple aspects of pharmacokinetics. Gastric acid secretion, gastrointestinal blood flow, proportions of muscular and adipose tissue, the amount of drug-binding proteins, gender-specific changes in the available amount of P450 isozymes, physiologic and hormonal changes during the menstrual cycle, and differences in renal blood flow are several factors that may have some bearing on sex-related differences in pharmacokinetics. Furthermore, female-specific issues such as pregnancy, menopause, oral contraceptive use, and menstruation may independently influence drug metabolism and serve as confounders to the interpretation of gender differences in drug handling or effect. While gender-related pharmacodynamic data are limited, evidence suggests that women are more prone to the development of torsade de pointes from proarrhythmic drugs such as quinidine or d-sotalol and have an increased cardiovascular risk with the use of digoxin. The specific risk:benefit ratio for individual cardiovascular medications should be more routinely considered in the context of gender.

Cardiotonic Agents↗

PubMedDate not supplied

Comparison of the degree of pulpal anesthesia achieved with the intraosseous injection and infiltration injection using 2% lidocaine with 1:100,000 epinephrine.

This prospective, randomized study compared the degree of pulpal anesthesia obtained from an intraosseous injection to an infiltration injection that used 2% lidocaine with 1:100,000 epinephrine. The success rate for the intraosseous injection was 98%; for the infiltration injection, the success rate was 85%. There was no significant difference between the two techniques. The mean time for the onset of pulpal anesthesia was significantly faster with the intraosseous injection and the infiltration injection resulted in a significantly longer duration of pulpal anesthesia.

Adult↗