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Biomedical subjects

C R Smith

Publications and source records attributed to C R Smith.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cardiac surgical patients exposed to heparin-bonded circuits develop less postoperative cerebral dysfunction than patients exposed to non-heparin-bonded circuits.

A prospective randomized trial was used to study the incidence of cerebral dysfunction in patients undergoing cardiopulmonary bypass (CPB) with heparin-bonded vs non-heparin-bonded circuits. Although the etiology of postoperative cerebral dysfunction is controversial, activation of the systemic inflammatory response may play a role. After institutional approval and informed written consent, 39 elective coronary artery bypass (CABG) patients were studied. A battery of neuropsychometric tests (NPMTs) was performed preoperatively, and 5 days and 6 weeks postoperatively. Significant change in NPMT performance was defined as a 25% or greater decrease in postoperative performance, compared to baseline. The number of abnormal tests per patient was calculated. Analysis using the Mann-Whitney rank test was performed for the first follow-up. Patients randomized to heparin-bonded circuits had fewer abnormal NPMTs (>1 abnormal test) on postoperative day 5 (58 vs 70%, n=19 and 20) than patients randomized to non-heparin-bonded circuits. Patients exposed to heparin-bonded circuits had fewer abnormal tests (>1 abnormal test) at 6 weeks (36 vs 63%, n=14 and 16). Results suggested that the attenuation of systemic inflammation by heparin-bonded CPB circuits may lower the incidence of cerebral injury in cardiac surgical patients.

Cardiopulmonary Bypass↗
PubMed2001

Assessment of left ventricular systolic function using contrast two-dimensional echocardiography with a high-frequency transducer in the awake murine model of myocardial infarction.

The estimation of global left ventricular function using M-mode echocardiography has technical limitations in the murine model of myocardial infarction (MI), but the recent improvements in 2-dimensional (2-D) echocardiography using a high-frequency transducer provide more accessible images. Furthermore, intravenous injection of contrast agent has the additional benefit of enhancing the endocardial border in the murine heart. The present study was designed to evaluate the value of 2-D echocardiography with intravenous injection of contrast agent in the assessment of global systolic function of the murine heart with MI. Two-dimensional and M-mode echocardiography without and with intravenous injection of contrast agent (Optison, 0.1-0.15 ml) were performed in 76 awake mice 2 days before and 2 days after left coronary artery ligation. Fractional shortening (FS) was calculated from the end-diastolic and end-systolic diameters on M-mode echocardiography, and fractional area change (FAC) from the end-diastolic and end-systolic areas on 2-D echocardiography. Both FS and FAC were compared with the areas of hypoperfusion observed in the pathological samples. The use of contrast agent improved the number of hearts that could be evaluated by both the M-mode and 2-D method (M-mode: non-contrast 87% vs contrast 99%, p<0.01; 2-D: non-contrast 26% vs contrast 89%, p<0.001). FAC from the 2-D method correlated better with the region of hypoperfusion in the pathological samples than did FS from the M-mode method (FAC: r=0.84 vs FS: r=0.51). In conclusion, FAC obtained from 2-D contrast echocardiography is useful for noninvasive assessment of global systolic function in infarcted murine hearts and can be used to serially assess systolic function in various models of the murine heart.

Albumins↗
PubMed2001

Tunica vaginalis for correcting penile chordee in a rabbit model: is there a difference in flap versus graft?

PURPOSE: We compared tunica vaginalis applied as a flap versus a graft for covering defects in the ventral tunica albuginea in a rabbit model. MATERIALS AND METHODS: We used 18 New Zealand White rabbits in the study. The urethra was mobilized off of the corpus cavernosum. A defect was created in the ventral aspect of the tunica albuginea by excising a 1 x 0.5 cm. rectangular area. The defect was covered by the testicular surface of tunica vaginalis as a vascularized flap in 9 animals and as a graft in 9. At 2, 6 and 12-week intervals 3 animals per group were sacrificed. Transverse sections of the penis at the repair site were stained with hematoxylin and eosin, and Masson's trichrome for microscopy. RESULTS: Autopsy revealed no contracture in any of the tunica vaginalis flaps. In contrast, the tunica vaginalis grafts had contracted by a mean of 22% (range 20% to 25%) at 2, 38% (range 30% to 44%) at 6 and 42% (range 38% to 48%) at 12 weeks. Microscopic examination of the tunica vaginalis flaps showed evidence of an intact blood supply and viable cremasteric muscle layer but no evidence of necrosis. Collagen remodeling and maturation was noted at 12 weeks. In tunica vaginalis grafts there was evidence of necrosis of all tunica vaginalis layers at 2 weeks with granulation tissue and active fibrosis at the periphery. At 6 and 12 weeks most necrotic tissue was replaced by fibrosis. Osseous metaplasia was identified in 1 graft at 12 weeks. CONCLUSIONS: The optimal use of tunica vaginalis for correction of chordee is as a flap rather than as a free graft. Grafts were associated with significant necrosis and contracture, of which neither was associated with flaps.

Animals↗
PubMed2000

Brief cyclosporine treatment prevents intrathymic (IT) tolerance induction and precipitates acute rejection in an IT rat cardiac allograft model.

BACKGROUND: Intrathymic (IT) alloantigen combined with administration of rabbit anti-rat anti-lymphocyte serum (ALS) intraperitoneally induces donor-specific tolerance to rat cardiac transplants. The purpose of this study was to examine the effect of a brief course (4 days) of cyclosporine (CsA) on the development of IT tolerance. METHODS: Buffalo (BUF) (RT1b) rats were given 25x10(6) fully MHC-mismatched Lewis (LEW) (RT1l) splenocytes by IT injection plus 1.0 ml of ALS intraperitoneally. Twenty-one days later, IT donor-specific LEW (group 1) or third-party (ACI, RT1a) (group 2) hearts were heterotopically transplanted to the abdominal aorta A third group of BUF (group 3) were given daily CsA (10 mg/kg) by oral gavage for 4 days before administration of IT LEW cells and ALS. Rejection as defined by the cessation of a palpable heartbeat was confirmed by histology. Cytokine profiles of allografts from all groups were then analyzed using a multi-probe RNase protection assay. RESULTS: Sixty-seven percent of IT/ALS-treated BUF recipients not pretreated with CsA accepted LEW heart grafts for greater than 90 days. However, 86% of animals treated with CsA for 4 days before IT injection and ALS rejected allografts at 10.7+/-3.2 days. Third-party allografts (ACI) were uniformly rejected (7.0+/-0.0 days). Histology confirmed cellular rejection in CsA-treated allografts and cytokine analysis detected increased interleukin (IL)-3, IL-5, and tumor necrosis factor-alpha when compared to increased IL-2 and interferon-gamma in rejecting untreated controls. CONCLUSIONS: CsA can prevent the induction of intrathymic alloantigen tolerance. These results support the development of a CsA-sensitive, but IL-2-independent, active regulatory mechanism after intrathymic exposure to donor-specific alloantigen and depletion of mature peripheral T cells.

Animals↗
PubMed2000

Cadaveric versus living donor kidney transplantation: a Medicare payment analysis.

BACKGROUND: We found previously that the clinical advantages of living donor (LD) renal transplantation lead to financial cost savings compared to either cadaveric donation (CAD) or dialysis. Here, we analyze the sources of the cost savings of LD versus CAD kidney transplantation. METHODS: We used United States Renal Data System data to merge United Network for Organ Sharing registry information with Medicare claims data for 1991-1996. Information was available for 42,868 CAD and 13,754 LD transplants. More than 5 million Medicare payment records were analyzed. We calculated the difference in average payments made by Medicare for CAD and LD for services provided during the first posttransplant year. RESULTS: Average total payments were $39,534 and $24,652 for CAD and LD, respectively (P<0.0001) during the first posttransplant year. The largest source of the difference in payments was in inpatient hospitals, representing $10,653.67 (P<0.0001). For patients who had Medicare as the primary payer, average transplant charges were significantly higher for CAD donation ($79,730 vs. $69,547, P<0.0001); average transplant payments demonstrated no statistical differences ($28,483 vs. $28,447, P = 0.858). Therefore, inferred profitability was significantly higher for LD. CONCLUSIONS: Medicare payments are remarkably lower for LD compared to CAD in every category. The single largest cost saving comes from inpatient hospital services. A portion of the savings from LD could be invested in programs to expand living kidney donation.

Cadaver↗
PubMed2000

Radio frequency transmyocardial revascularization enhances angiogenesis and causes myocardial denervation in canine model.

BACKGROUND AND OBJECTIVE: Transmyocardial revascularization (TMR) relieves angina and improves exercise tolerance in patients. Angiogenesis and myocardial denervation have been proposed as factors contributing to these benefits. To test whether radio frequency transmyocardial revascularization (RF-TMR) enhances angiogenesis and causes myocardial denervation. STUDY DESIGN/MATERIALS AND METHODS: RF-TMR channels were created in 12 dogs which survived up to 4 weeks. Bromodeoxyuridine was administered subcutaneously to mark proliferating cells as an assay of angiogenesis. Western blot analysis of tyrosine hydroxylase and blood pressure response to topical bradykinin were used as indices of myocardial denervation. RESULTS: RF-TMR increased local vascularity by an average of 50%, whereas the rate of vascular cell proliferation was tripled over that of the untreated region. Changes in mean arterial pressure with bradykinin and tyrosine hydroxylase content were significantly decreased in RF-TMR regions as compared with normal myocardium in the same hearts. CONCLUSION: RF-TMR enhances angiogenesis and causes myocardial denervation in canine myocardium as with laser TMR.

Animals↗
PubMed2000

Histologic evidence that basic fibroblast growth factor enhances the angiogenic effects of transmyocardial laser revascularization.

OBJECTIVES: To determine whether addition of basic fibroblast growth factor (bFGF), an angiogenic growth factor, enhances the angiogenic effects of transmyocardial laser revascularization (TMR). BACKGROUND: TMR is an investigational therapy for treating patients with medically refractory angina not amenable to traditional therapies. Histologic and blood flow studies in animals have suggested that TMR enhances angiogenesis above that normally seen in ischemic myocardium. We tested the hypothesis that bFGF administered into TMR channels further enhance the angiogenic effects of TMR. METHODS: Chronic ischemia was created in 3 groups of dogs using an ameroid constrictor on the proximal LAD. In the bFGF group (n = 5) non-transmyocardial channels were created in the LAD territory and bFGF, (100 ng/ml) dissolved in pluronic gel was injected into the each channel. In the TMR group (n = 7), transmyocardial channels were created without bFGF. A control group (n = 7) had ischemia without TMR of bFGF. 5-bromo-2'-deoxyuridine (BrdU) was administered to mark proliferating cells. After 8 weeks survival, colored microspheres were injected to assess the regional myocardial blood flow. RESULTS: TMR and TMR+bFGF increased total vascular density by approximately 40% over that observed in the control group. However, the number of large vessels (internal diameter > or = 50 microm) was doubled by the addition of bFGF, and this correlated with a 50% increase in the density of proliferating vascular cells and a tripling of the total estimated vascular cross sectional area. Blood flow to the LAD territory was increased by TMR compared to controls, with no further benefit observed in the bFGF group. CONCLUSIONS: On a histologic basis, basic fibroblast growth factor further enhances angiogenesis following TMR in ischemic myocardium mainly by increasing the size but not the total number of vessels.

Animals↗
PubMed2000

Multicenter review of preoperative risk factors for stroke after coronary artery bypass grafting.

BACKGROUND: Stroke complicates the postoperative course in 1% to 6% of patients undergoing coronary revascularization. There has been no large scale mandatory database reporting on the incidence of stroke after coronary revascularization. METHODS: A multicenter regional database from the Bureau of Health Care Research Information Services, New York State Department of Health, on 19,224 patients who underwent coronary revascularization in 31 hospitals within New York State during 1995 was analyzed to determine the risk factors for postoperative stroke. RESULTS: The incidence of postoperative stroke was 1.4% (n = 270). Hospital mortality for patients who had a stroke was 24.8%, compared with 2.0% for the rest of the patient population. Postoperative stroke increased the hospital length of stay threefold (27.9+/-1.9 versus 9.1+/-0.9 days, p<0.0001). Multivariable logistic regression identified the following variables to be significantly associated with a postoperative stroke: calcified aorta (p<0.0001; odds ratio [OR], 3.013), prior stroke (p = 0.0003; OR, 1.909), age (p<0.0001; OR, 1.522 per 10 years), carotid arterial disease (p = 0.002; OR, 1.590), duration of cardiopulmonary bypass (p = 0.0004; OR, 1.27 per 60 minutes), renal failure (p = 0.0062; OR, 2.032), peripheral vascular disease (p = 0.0157; OR, 1.62), cigarette smoking (p = 0.0197; OR, 1.621), and diabetes mellitus (p = 0.0158; OR, 1.373). CONCLUSIONS: Postoperative stroke increases mortality and length of stay after coronary revascularization. Several risk factors can be identified, and some of these factors are potentially amenable to intervention, either before or during coronary revascularization, and should also influence patient selection.

Adult↗
PubMed2000

Airway epithelial cell damage mediated by antigen-specific T cells: implications in lung allograft rejection.

The aim of this study is to assess the mechanisms associated with airway epithelial cell (AEC) injury, which may have implications in lung allograft rejection. Three AEC lines, KDI-650, Beas-2B and A549 were analyzed. Effect of cytokines on the expression of Fas, HLA class I, and HLA class II were assessed by flow cytometry. AEC-specific T cells were generated in vitro and assessed for lysis by (51)Cr release assay. HLA class I and Fas were expressed on all AEC lines. Beas-2B and A549 expressed low levels of class II compared with KDI-650, which lack this expression. Expression of HLA class II was augmented on KDI-650 and Beas-2B by IFN-gamma treatment. AEC-specific T cells generated in vitro were predominantly CD8(+) and lysed relevant AEC targets. Anti-HLA class I monoclonal antibodies inhibited the lysis of AEC by specific T cells while anti-Fas and anti-HLA class II monoclonal antibodies did not have any effect on the T cell induced lysis of AECs. AECs cultured with supernatant derived from T-cell cultures induced the expression of Fas, HLA class I, as well as HLA class II. These results suggest AEC damage is mediated by AEC-specific T cells primarily by the conventional HLA class I/peptide complex and TCR interaction. Further, the factors released by these T cells also induce the expression of Fas, as well as HLA class I and class II, which may have implications on the outcome of the immune response against AECs.

Antibodies, Monoclonal↗
PubMed2000

Purification and characterization of cytosolic pyruvate kinase from Brassica napus (rapeseed) suspension cell cultures: implications for the integration of glycolysis with nitrogen assimilation.

Cytosolic pyruvate kinase (PKc) from Brassica napus suspension cells was purified 201-fold to electrophoretic homogeneity and a final specific activity of 51 micromol phosphoenolpyruvate utilized per min per mg protein. SDS/PAGE and gel filtration analyses of the final preparation indicated that this PKc is a 220-kDa homotetramer composed of 56-kDa subunits. The enzyme was relatively heat-stable and displayed a broad pH optimum of pH 6.8. PKc activity was absolutely dependent upon the simultaneous presence of a bivalent and univalent cation, with Mg2+ and K+ fulfilling this requirement. Hyperbolic saturation kinetics were observed for phosphoenolpyruvate, ADP, Mg2+ and K+ (apparent Km values = 0.12, 0.075, 0.21 and 0.48 mM, respectively). Although the enzyme utilized UDP, CDP and IDP as alternative nucleotides, ADP was the preferred substrate. L-Glutamate, oxalate, and the flavonoids rutin and quercetin were the most effective inhibitors (I50 values = 4, 0.3, 0.07, and 0.10 mM, respectively). L-Aspartate functioned as an activator (Ka = 0.31 mM) by causing a 40% increase in Vmax while completely reversing the inhibition of PKc by L-glutamate. Reciprocal control by L-aspartate and L-glutamate is specific for these amino acids and provides a rationale for the in vivo activation of PKc that occurs during periods of enhanced NH +4-assimilation. Allosteric features of B. napus PKc are compared with those of B. napus phosphoenolpyruvate carboxylase. A model is presented that highlights the pivotal role of L-aspartate and L-glutamate in the coordinate regulation of these key phosphoenolpyruvate utilizing cytosolic enzymes.

Adenosine Diphosphate↗
PubMed2000

Impact of current management practices on early and late death in more than 500 consecutive cardiac transplant recipients.

OBJECTIVE: To study risk factors for early and late death after heart transplantation in the current era. SUMMARY BACKGROUND DATA: The current cardiac transplant population differs from earlier periods in that an increasing number of sicker patients, such as those with ventricular assist device (LVAD) support, prior cardiac allotransplantation, and pulmonary hypertension, are undergoing transplantation. In addition, sensitized patients constitute a greater proportion of the transplanted population. Emphasis has been placed on therapies to prevent early graft loss, such as the use of nitric oxide and improved immunosuppression, in addition to newer therapies. METHODS: Five hundred thirty-six patients undergoing heart transplantation between 1993 and 1999 at a single center were evaluated (464 adults and 72 children; 109 had received prior LVAD support and 24 underwent retransplantation). The mean patient age at transplantation was 44.9 years. Logistic regression and Cox proportional hazard models were used to evaluate the following risk factors on survival: donor and recipient demographics, ischemic time, LVAD, retransplantation, pretransplant pulmonary vascular resistance, and immunologic variables (ABO, HLA matching, and pretransplant anti-HLA antibodies). RESULTS: The rate of early death (less than 30 days) was 8.5% in adults and 8.8% in children. The actuarial survival rate of the 536 patients was 83%, 77%, and 71% at 1, 3, and 5 years, respectively, by Kaplan Meier analysis. Risk factors adversely affecting survival included the year of transplant, donor age, and donor-recipient gender mismatching. Neither early nor late death was influenced by elevated pulmonary vascular resistance, sensitization, prior LVAD support, or prior cardiac allotransplantation. CONCLUSIONS: Previously identified risk factors did not adversely affect short- or long-term survival of heart transplant recipients in the current era. The steady improvement in survival during this period argues that advances in transplantation have offset the increasing acuity of transplant recipients.

Adolescent↗
PubMed2000

Impact of recombinant baculovirus field applications on a nontarget heliothine parasitoid, Microplitis croceipes (Hymenoptera: Braconidae).

The kill times of two viruses infectious to the heliothine pest complex indigenous to Texas cotton have been significantly reduced by expressing a scorpion toxin gene. Autographa californica nucleopolyhedrovirus (NPV) and Helicoverpa zea NPV express the toxin only in permissive lepidopteran hosts. The toxin, however, could indirectly harm members of upper trophic levels that feed upon and parasitize infected larvae producing the toxin. In this study, the effects of recombinant and wild-type viruses on Microplitis croceipes (Cresson) were studied in cotton using Heliothis virescens (F.) (Lepidoptera: Noctuidae) as hosts. Two recombinant viruses, their two wild-type progenitor viruses, and untreated cotton served as the five treatments of study. Larvae were previously parasitized 2 and 4 d before being confined for 72 h to cotton terminals treated with field rates of virus or left untreated. The sexes of adult M. croceipes that emerged from the recovered H. virescens larvae were determined and their head capsule widths were measured. Polymerase chain reaction (PCR) searched their extracts for virus DNA. There were no differences in percentage emergence and sex ratios of parasitoids among recombinant, wild-type, and control treatments. Significantly more wasps emerged from the 4-d cohort, but these wasps were significantly smaller than wasps from the 2-d cohort regardless of treatment. Finally, PCR found only 15-25% of the recovered H. virescens larvae and none of the emergent M. croceipes had detectable levels of viral DNA. Recombinant and wild-type viruses had a similar, minimal impact on emergent wasps, and the probability of virus dispersal via parasitoids is low in the system tested.

Animals↗
PubMed2000

Ground penetrating radar surveys to locate 1918 Spanish flu victims in permafrost.

The "Spanish Flu" killed over 40 million people worldwide in 1918. Archival records helped us identify seven men who died of influenza in 1918 and were interred in Longyearbyen, Svalbard, Norway, 1,300 km from the North Pole. Ground Penetrating Radar (GPR) was used successfully, in a high-resolution field survey mode, to locate a large excavation with seven coffins, near the existing seven grave markers. The GPR indicated that the ground was disturbed to 2 m depth and was frozen below 1 m. Subsequent excavation showed that: a) the GPR located the position of the graves accurately, b) the coffins were buried less than 1 m deep, and c) that the frozen ground was 1.2 m deep where the coffins were located. The GPR assisted in planning the exhumation, safely and economically, under the high degree of containment required. Virologic and bacteriologic investigations on recovered tissues may give us an opportunity to isolate and identify the micro-organisms involved in the 1918 influenza and expand our knowledge on the pathogenesis of influenza.

Burial↗
PubMed2000

Influence of lung injury on early postoperative survival after lung transplantation.

OBJECTIVES: To identify the various risk factors for early (90 day) mortality after lung transplantation and to evaluate the relationship between lung injury and postoperative survival. METHODS: 152 recipients of single (100) or bilateral (52) lung allografts were evaluated for the presence of postoperative lung injury assessed by a composite four-component lung injury score. Preoperative variables, postoperative course, and mortality were reviewed retrospectively. RESULTS: There was a high risk of death during the first 90 d after transplantation, followed by a decline in risk during the remainder of the first postoperative year. By univariate analysis, lung injury score (p = 0.0001), chest radiograph score (p = 0.0001), and hypoxemia (PaO2/FIO2) ratio (p = 0.0002) were the most statistically significant risk factors for 90-day mortality. Other parameters such as length of intensive care stay (p = 0.0175), length of intubation (p = 0.0212), and preoperative diagnosis of pulmonary fibrosis (p = 0.0123) were also significant risk factors for 90-day mortality. By multivariable analysis, only lung injury score (p = 0.0001) was a statistically significant risk factor for 90-day mortality. The risk of 90-day mortality increased by a factor of 4.4 for each 1 point increment in lung injury score. However, none of the analyzed preoperative or postoperative variables were able to statistically predict lung injury score. CONCLUSIONS: Postoperative lung injury is the most important risk factor for early postoperative mortality after lung transplantation.

Adult↗
PubMed1999

Aprotinin in deep hypothermic circulatory arrest.

Early experience with aprotinin in deep hypothermic circulatory arrest (DHCA) raised alarm about hazards associated with its use. Based on what little is known about possible mechanistic interactions between hypothermia, stasis, and aprotinin, there is no evidence that aprotinin becomes unusually hazardous in DHCA. Excessive mortality and complication rates have only been reported in clinical series in which the adequacy of heparinization is questionable. Benefits associated with use of aprotinin in DHCA have been inconsistently demonstrated. The only prospective, randomized series showed significant reduction in blood loss and transfusion requirements. Use of aprotinin in DHCA should be based on the same considerations applied in other cardiothoracic procedures.

Aprotinin↗