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Biomedical subjects

S Houser

Publications and source records attributed to S Houser.

At least 19 recordsLinked to original sources

Three catheter-based strategies for cardiac delivery of therapeutic gelatin microspheres.

Gelatin hydrogel microspheres (GHMs) have been reported as novel non-viral vectors for gene or protein delivery (GHM therapy). However, the components of an effective catheter-based delivery strategy for GHM therapy are unknown. We evaluated the effectiveness of three catheter-based strategies for cardiac GHM therapy: (1) antegrade injection (AI) via coronary arteries; (2) retrograde injection (RI) via coronary veins; and (3) direct myocardial injection (DI) via the coronary sinus. AI distributed microspheres homogeneously throughout the target area with 73+/-11% retention. RI scattered microspheres non-homogenously with 22+/-8% retention. DI distributed microspheres in the needle-advanced area with 47+/-14% retention. However, despite high efficiency, AI did not show biological effects of inducing angiogenesis from basic fibroblast growth factor bound to GHMs. Furthermore, focal micro-infarctions, owing to micro-embolism of aggregated GHMs into small coronary arterioles, were detected in the AI group. Conversely, only RI and DI groups displayed increased coronary flow reserve. DI groups also demonstrated increased capillary density. These results suggest that RI and DI are effective for cardiac GHM therapy, while AI appears inappropriate owing to the risk of focal infarctions.

Animals↗

Troponin T levels in baboons with pig heterotopic heart transplants.

Troponin T levels have been monitored in baboons (n = 8) undergoing pig heterotopic heart transplantation, and correlated with a decrease in graft contractions and graft survival. Pig heart graft survival was from 12 to 139 days (mean 45, median 33), and graft failure was associated with predominant thrombotic microangiopathy and ischemia, with focal hemorrhage, and edema. An increase in troponin T levels 5 to 6 days before graft failure correlated closely with diminished graft contractions. An increase in troponin T was a reliable indicator that graft dysfunction was occurring.

Animals↗

Camptothecin and Zeocin can increase p53 levels during all cell cycle stages.

The ability of DNA damage to stabilize p53 in all cell cycle stages has not been examined in actively growing cells. The chemotherapeutic drug camptothecin is a topoisomerase I poison. Zeocin is a member of the bleomycin/phleomycin family of antibiotics, known to bind DNA. Both increase the level of p53 albeit by different mechanisms. We have utilized centrifugal elutriation to separate exponentially growing ML-1 cells (containing wild-type p53) into cell cycle fractions and have subsequently treated these cells with the two drugs. We provide evidence that both drugs can mediate an increase in p53 protein levels independent of the cell cycle stage. The p53 induced by both drugs was able to bind to DNA; however, only the p53 induced by camptothecin was phosphorylated at serine-392. This is the first demonstration that camptothecin and Zeocin can differentially signal for increased levels of modified p53 during all stages of the cell cycle.

Antibiotics, Antineoplastic↗

Mixed hematopoietic chimerism induces long-term tolerance to cardiac allografts in miniature swine.

BACKGROUND: Tolerance to cardiac allografts has not been achieved in large animals using methods that are readily applicable to human recipients. We investigated the effects of mixed hematopoietic chimerism on cardiac allograft survival and chronic rejection in miniature swine METHODS: Recipients were T-cell depleted using a porcine CD3 immunotoxin, and each received either of two nonmyeloablative preparative regimens previously demonstrated to permit the establishment of stable mixed hematopoietic chimerism across MHC-matched, minor antigen-mismatched histocompatibility barriers. Five to 12 months after the chimerism was induced, hearts from the original cell donors were heterotopically transplanted into the stable mixed chimeras. RESULTS: Cardiac allografts transplanted into untreated recipients across similar minor antigen barriers were rejected within 44 days (within 21, 28, 35, 39, 44 days among individual study subjects). In contrast, hearts transplanted into the mixed chimeras were all accepted long term ( > 153, > 225, > 286, > 362 days) without immunosuppressive drugs and developed minimal vasculopathy. CONCLUSIONS: Mixed hematopoietic chimerism, established in miniature swine using clinically relevant, non-myeloablative conditioning regimens, permits long-term cardiac allograft survival without chronic immunosuppressive therapy, significant vasculopathy, or graft-versus-host disease.

Animals↗

Acoustic rhinometry and computed tomography scans for the diagnosis of nasal septal deviation, with clinical correlation.

OBJECTIVE: The aim in this study was to analyze the efficiency and reliability of acoustic rhinometry (AR) readings in recognition of nasal septal deviation. METHOD: We compared 24 patients' AR readings with their sinus CT scans. The patient data were analyzed by comparison with normative data, area, and percentage differences between the two sides. Additionally, the data further analyzed by receiver operating characteristic curve and Spearman correlation of CT and AR in determining nasal septal deviation. RESULTS: The sensitivity of AR in detecting anterior septal deviations was found to be 54%, with a specificity of 70%. A very highly significant correlation (P < or = 0.001) was found between minimal cross-sectional area (CSA) 1 values and CT results. DISCUSSION: In the interpretation of AR readings, comparison of each CSA value should be included, in addition to use of the total absolute CSA values. CONCLUSION: According to our findings the diagnosis of nasal septal deviation can be supported by AR readings.

Acoustics↗

Measuring self-efficacy in substance abuse intervention in obstetric practices.

BACKGROUND: This study presents findings on the effect of an office-based obstetrics training program (given the acronym OBIWOM) on substance use assessment, management, and referral self-efficacy among obstetricians and staff of private, community-based obstetric practices. METHODS: Participants were obstetricians and staff from 10 of 27 available community-based, private obstetric practices in the target areas, for a practice participation rate of 37%. This study used a delayed treatment design to compare self-efficacy between practice staff randomly assigned to an immediate or delayed intervention group. RESULTS: Self-efficacy increased significantly after intervention from baseline to first follow-up for the immediate group, while no change was shown for the delayed (control) group. The impact of the intervention on self-efficacy was replicated in the assessment construct only after the intervention for the delayed group. CONCLUSION: This research shows that education and training can effectively improve self-efficacy in obstetricians and their staff in the management of substance use and pregnancy.

Adult↗

Functional arteries grown in vitro.

A tissue engineering approach was developed to produce arbitrary lengths of vascular graft material from smooth muscle and endothelial cells that were derived from a biopsy of vascular tissue. Bovine vessels cultured under pulsatile conditions had rupture strengths greater than 2000 millimeters of mercury, suture retention strengths of up to 90 grams, and collagen contents of up to 50 percent. Cultured vessels also showed contractile responses to pharmacological agents and contained smooth muscle cells that displayed markers of differentiation such as calponin and myosin heavy chains. Tissue-engineered arteries were implanted in miniature swine, with patency documented up to 24 days by digital angiography.

Animals↗

Infrared spectroscopy of human tissue. V. Infrared spectroscopic studies of myeloid leukemia (ML-1) cells at different phases of the cell cycle.

Infrared spectra of myeloid leukemia (ML-1) cells are reported for cells derived from an asynchronous, exponentially growing culture, as well as for cells that were fractionated according to their stage within the cell division cycle. The observed results suggest that the cells' DNA is detectable by infrared spectroscopy mainly when the cell is in the S phase, during the replication of DNA. In the G1 and G2 phases, the DNA is so tightly packed in the nucleus that it appears opaque to infrared radiation. Consequently, the nucleic acid spectral contributions in the G1 and G2 phases would be mostly that of cytoplasmic RNA. These results suggest that infrared spectral changes observed earlier between normal and abnormal cells may have been due to different distributions of cells within the stages of the cell division cycle.

Cell Cycle↗

Quantitative determination of theophylline by an automated chemiluminescent immunoassay in serum and plasma: comparison to other methods of analysis.

A chemiluminescent immunoassay for theophylline in serum or plasma was developed for the Ciba Corning ACS: 180 automated analyzer. The assay has a limit of quantitation of 0.2 microgram/ml, with a range up to 40 micrograms/ml. The cross-reactivity to metabolites 1,3-dimethyluric acid 3-methylxanthine was 3.4% and 2.5%, respectively. Overall means of 101.0% and 97.8% were determined from dilution linearity and addition studies, respectively. When compared to a high-performance liquid chromatography (HPLC) method, a linear regression of ACS Theophylline = 0.996 (HPLC) + 0.35, r = 0.991, n = 93, was obtained. Similar results were obtained when the ACS assay was compared to other immunoassays. Precision (within-run and total coefficient of variation or CV) was < 6% in the therapeutic range (10-20 micrograms/ml). The performance data demonstrate that the ACS Theophylline assay provides an additional choice for the clinical measurement of the drug.

Chromatography, High Pressure Liquid↗

Intraoperative radiation therapy and Mohs micrographic surgery on an outpatient basis.

BACKGROUND: Intraoperative radiation therapy (IORT) is used to deliver therapeutic doses of radiation to a surgically exposed tumor or tumor bed while minimizing the radiation dose to adjacent normal tissue. It is traditionally given with the patient under general anesthesia. OBJECTIVE: To report a case of a recurrent squamous cell carcinoma treated with Mohs micrographic surgery and IORT on an outpatient basis. METHODS: Mohs surgery was used to clear the tumor in all fields except for the area of the spinal accessory nerve, which was preserved. IORT was then delivered to the area of nerve with possible residual tumor. RESULTS: The patient remains clinically tumor free 42 months posttreatment. There were no complications. CONCLUSION: Intraoperative radiation therapy can be effectively used in the outpatient setting as an adjunctive therapy after Mohs micrographic surgery.

Ambulatory Surgical Procedures↗

Predictors of perioperative morbidity and mortality in repeat valve replacement: a seven-year experience.

Forty-nine consecutive repeat cardiac valve replacements in 46 patients were reviewed to define in-hospital morbidity, mortality, and determinants of risk. The overall operative mortality rate was 10.2%; it was 9% for the first reoperation and 25% for the second (four patients). The mortality rate was 12% at the mitral position (25 patients), 11% at the aortic position (18 patients), and 0% for repeat double valve replacement (four patients). Univariate and multivariate stepwise logistic regression models show that age over 70 years and the use of an intraaortic balloon pump preoperatively predict operative mortality, and age over 70, preoperative care in the coronary care unit, endocarditis, and the presence of an intraaortic balloon pump are determinants of perioperative morbidity in patients undergoing repeat valve replacement. Based on these data, close follow-up of patients with initial valve replacement is encouraged so that reoperation to correct prosthetic malfunction or periprosthetic leak can be done before hemodynamic collapse occurs. Furthermore, since age was the most significant factor affecting mortality (P < .01) and since most of the deaths (80%) in this study occurred in patients with torn bioprosthetic leaflets, the use of bioprostheses for initial valve replacement in patients under 70 years of age is discouraged.

Adult↗

Cyclocreatine inhibits neutrophil accumulation in the myocardium of a canine model of coronary artery occlusion and reperfusion.

This study tests the hypothesis that the administration of cyclocreatine before ischemia inhibits the release of neutrophil chemotactic factors from myocardial tissues and subsequently reduces neutrophil accumulation into ischemic areas. Adult mongrel dogs underwent left anterior descending coronary artery occlusion for 1 h, followed by a 2-h reperfusion. Cyclocreatine-treated dogs (n = 6) were injected intravenously with cyclocreatine solution (600 mg/kg) 1 h before the experiment and during ligation of the coronary artery. Control dogs (n = 6) were injected with saline. Neutrophil chemotactic activity was measured in plasma samples using standard modified Boyden chambers. In controls dogs, significantly elevated levels of chemotactic activity were recovered in blood samples taken during reperfusion (i.e., 2.8-3.5-fold; P < .0001) as compared to base-line activity recovered before occlusion. Preliminary biochemical characterizations revealed that the recovered chemotactic factors (via checkerboard analysis) are proteins of high molecular weight (greater than 100 kDa). Biopsy samples of control hearts showed an accumulation of a large number of neutrophils in the ischemic portions. Cyclocreatine-treated dogs, on the contrary, showed low levels of chemotactic activity during reperfusion, which correlated with the absence of neutrophils in ischemic areas. These results indicate the capability of cyclocreatine to inhibit the release of neutrophil chemotactic factors from ischemic myocardium, which subsequently prevented neutrophil accumulation.

Amino Acid Sequence↗

Norepinephrine-induced cardiac hypertrophy of the cat heart.

Norepinephrine administration causes progressive hypertrophy of the mammalian heart as measured by myocardial mass. The purpose of this study was to determine the growth response of the myocardial tissue components as well as the myocardial cell itself to norepinephrine. Young, adult cats were given low doses of norepinephrine in dextrose or dextrose alone twice daily for 15 days. On day 16, there were no changes in the animals body weight, right ventricular systolic pressure, right ventricular end-diastolic pressure, heart rate, cardiac index, or blood pressure. However, the right ventricle/body weight, the left ventricle/body weight and the total heart weight/body weight were increased significantly in the norepinephrine treated animals. The increase was on the order of 40%. The cardiac muscle cell was also significantly increased in size and both the right and left ventricular cardiac muscle cells exhibited a dramatic increase in size as measured by cross sectional area. Upon stereological examination it was found that the amount of hypertrophy as seen in the cardiac muscle cells was paralleled by the hypertrophy seen in the other tissue components of the myocardium. The volume density of the muscle cells, the interstitial components, as well as the blood vessel compartment were identical in the control and in the norepinephrine-treated groups. In conclusion, this study demonstrates that the response of the myocardium to norepinephrine is similar to that seen in response to a volume overload rather than that seen in response to pressure overload.

Animals↗

Hypertrophy without contractile dysfunction after reversal of pressure overload in the cat.

To determine whether a causal relationship exists between the myocardial hypertrophy and the deficits in myosin ATPase activity and contractile function that have been associated with chronic, experimental pressure overload, we studied contractile function, myosin ATPase, and isomyosin pattern in a model of severe pressure overload in which the pressure overload was surgically relieved but hypertrophy persisted. Severe hypertrophy, contractile dysfunction, and pump failure were produced in the cat right ventricle by tight pulmonary arterial banding. In two groups of cats banded for 2- and 7-wk periods, right ventricular mass doubled, and contractile function was severely depressed compared with controls. In another group of cats subjected to severe right ventricular pressure overload for 4 wk, pressure overload was reversed by removal of the pulmonary arterial band. After a 4-wk recovery period for this group, right ventricular mass remained markedly increased, but contractile function had returned to normal. Changes in neither isomyosin composition nor myosin ATPase activity were found regardless of contractile function. Thus, following reversal of a right ventricular pressure overload severe enough to cause pump failure and a twofold increase in right ventricular mass, muscle contractile function can return to normal even when severe hypertrophy persists. Furthermore, changes in myosin isozyme composition or ATPase activity do not explain the changes in contractile function.

Adenosine Triphosphatases↗

Management of fusiform ascending aortic aneurysms.

Thirteen patients had elective surgical treatment of fusiform ascending aortic aneurysms at Strong Memorial and Rochester General Hospitals from 1970 to 1978. There were 8 men and 5 women ranging in age from 51 to 78 years (mean, 61 years). Nine patients underwent composite tube graft and aortic valve replacement, 3 had aortic valve replacement plus supracoronary tube grafts, and 1 had aortic valve replacement plus aneurysmorrhaphy. Coronary reimplantation alone or combined with saphenous vein bypasses was fashioned in 10 patients. Potassium cardioplegia was considered a useful adjunct in 6 patients. Two early deaths accounted for an operative mortality of 15.4%. There were 3 late deaths. Eight patients are alive and well 2 to 109 months after operation.

Aged↗

Rhabdomyoma of the heart: a diagnostic and therapeutic challenge.

The sector scan was decisive in establishing the diagnosis of multiple rhabdomyomas of the heart in a newborn infant. Successful resection of the tumors was performed with profound hypothermia and limited cardiopulmonary bypass. Nine months later, the infant died of the complications of tuberous sclerosis. This case report documents the diagnostic accuracy of the sector scan and the potential benefit of aggressive surgical management of this condition.

Diagnosis, Differential↗

Analysis of frequency of pulmonary atelectasis in patients undergoing pectoralis major musculocutaneous flap reconstruction.

The incidence of pulmonary atelectasis following head and neck surgery is not well reported. This study retrospectively evaluated the incidence of pulmonary atelectasis in 161 head and neck cancer patients, with 152 being evaluable. There were 90 patients evaluated following pectoralis musculocutaneous flap reconstruction with their effective flap size and 71 nonflap patients as a control group. Clinical findings were correlated to radiographic scores. Of pectoralis musculocutaneous flap patients screened for preexisting pulmonary disease (PEPD), nine of 45 (20%) demonstrated pulmonary atelectasis in the first 24 hours compared with 10 of 39 or 25.6% nonflap controls. Major pulmonary atelectasis was not found in the pectoralis musculocutaneous flap patients by scoring criteria, and in only one of 39 (2.6%) nonflap patients. In flaps larger than 40 cm2, the incidence was eight of 37 (21.6%), with no major pulmonary atelectasis noted. Only one of nine (11.1%) patients with radiographic pulmonary atelectasis exhibited clinical symptoms (three of 10 or 30% control). In patients with PEPD and pectoralis musculocutaneous flaps, 22 of 45 (48.9%) had evidence of pulmonary atelectasis in contrast to 13 of 32 or 40.6% controls. There were two of 45 (4.4%) who had major pulmonary atelectasis with zero of 32 in the nonflap group. For flaps larger than 40 cm2, the incidence was 19 of 39 (48.7%) with two of 39 (5.1%) scored as major pulmonary atelectasis. The clinical correlation for this group and the major pulmonary atelectasis group was each approximately 50% compared to 15.4% for nonflap patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Comorbidity↗