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Biomedical subjects

C R Smith

Publications and source records attributed to C R Smith.

At least 73 records · Page 4Linked to original sources

Urethral replacement with vascularized tunica vaginalis: defining the optimal form of use.

PURPOSE: Residual urethral defects after failed hypospadias surgery present difficulties in reconstruction. In these situations, repair using vascularized tissue flaps remains ideal, yet challenging. In order to offer more surgical alternatives in these cases, the use of vascularized tunica vaginalis flaps as urethral replacements has recently been established in an animal model. We undertook the following studies to further define the role of tunica vaginalis in urethral reconstruction. MATERIALS AND METHODS: A vascularized flap of tunica vaginalis was used to replace an experimentally created 25-30 mm. gap in the anterior urethra of 26 rabbits, either as an onlay or tube flap. A control group consisting of 7 animals underwent only a segmental anterior urethral resection and primary re-anastomosis. RESULTS: Satisfactory urethral healing occurred in all control animals that survived the procedure. All 8 animals which had tunica vaginalis tube flap reconstruction underwent contracture of the neourethra probably secondary to the presence of striated cremasteric muscle elements brought with the tunica during mobilization. All 16 animals available for long term study in the onlay flap group had excellent flap viability and 100% urethral patency rates. The mesothelial lining of the tunica was seen to be replaced by a stratified epithelial lining similar to the urothelial lining of the native urethra. CONCLUSION: The tunica vaginalis is a viable alternative to other tissues presently used for urethral replacement and can be used successfully as a vascularized onlay flap.

Animals↗

Vestimentiferan on a whale fall.

Discovery of chemosynthetic communities associated with whale bones led to the hypothesis that whale falls may serve as stepping-stones for faunal dispersal between disjunct hydrothermal vents and cold seeps on the ocean floor (1). The initial observation was followed by a faunal inventory that revealed a diverse assemblage of microbes and invertebrates, supported by chemoautotrophic production, living in close proximity to whale remains (2, 3). To date, the conspicuous absence from whale falls of vestimentiferan tubeworms (a predominant constituent of eastern Pacific vent and seep habitats) has been a major objection to the stepping-stone hypothesis (4-5). We report the first evidence of a vestimentiferan tubeworm associated with a whale fall (Fig. 1). The tubeworm, Escarpia spicata, was identified by morphological criteria and DNA sequence data from a portion of the mitochondrial cytochrome oxidase C subunit I (COI) gene. Additionally, the bacterial endosymbiont in the tubeworm possessed a 16S rRNA gene that was similar to that of endosymbionts from vestimentiferans in sedimented cold-seep environments.

Animals↗

Determining when integrated delivery systems should belong to GPOs.

Membership in national group purchasing organizations (GPOs) is a proven way for healthcare organizations to access supply price discounts through collectively negotiated contracts. Yet, for various reasons, both suppliers and healthcare materials managers have expressed dissatisfaction with GPOs. Integrated delivery systems (IDSs), in particular, may find that negotiating with suppliers independently is a more cost-effective alternative. Whether an IDS should participate in group purchasing or negotiate with suppliers on its own depends on the following factors: whether the IDS would find it relatively simple to get its clinicians to standardize on certain key supplies; whether the IDS has sufficient staff to devote to contracting; whether the benefits offered by the GPO do not outweight the costs of membership; and whether all of the supplier products and services the GPO makes available also are available through second-tier suppliers eager to negotiate directly with the IDS.

Consumer Behavior↗

Role of cardiopulmonary bypass in single vessel coronary revascularization: implications for MID-CABG.

BACKGROUND: Minimally invasive direct coronary artery bypass grafting (MID-CABG) is being utilized for the treatment of coronary artery disease in selected patients. This innovative procedure has generated numerous technical issues relating to coronary revascularization, including whether to perform the revascularization with or without cardiopulmonary bypass (CPB). METHODS: We addressed this issue indirectly by analyzing the 1995 New York State CABG registry, comparing patients who had single vessel bypass without CPB (Non-CPB Group) to a similar cohort of patients who had CABG performed on CPB (CPB Group). The database showed stratification of patients selected for bypass grafting without CPB to a significantly higher risk group, as shown by increased age, higher incidence of reoperation, transmural MI, congestive heart failure, carotid/cerebrovascular disease, and peripheral vascular disease. RESULTS: Patients in the Non-CPB Group had a higher incidence of postoperative malignant ventricular arrhythmias and heart block requiring pacemaker insertion. Otherwise, the incidence of postoperative complications was similar between the two groups. CONCLUSIONS: There were no statistical differences in the hospital mortality or the length of hospitalization between the two groups. In conclusion, the data showed a definite trend toward doing higher risk cases off CPB. These cases had an acceptable early morbidity and mortality outcome. The results were comparable to a group of lower risk patients with single vessel CABG done on cardiopulmonary bypass. However, further follow-up are required to evaluate long-term outcomes and confirm the utility of this surgical option.

Aged↗

A prospective randomized trial of arginine vasopressin in the treatment of vasodilatory shock after left ventricular assist device placement.

BACKGROUND: Vasodilatory shock requiring catecholamine pressors occurs in some patients following cardiopulmonary bypass. Prompted by a clinical observation, we investigated the use of vasopressin as a treatment for this syndrome in a randomized, controlled trial. METHODS AND RESULTS: Patients undergoing placement of a left ventricular assist device (n=23) were evaluated for post-bypass vasodilatory shock requiring catecholamine pressors, and consecutive eligible subjects (n=10) were evenly randomized to blinded intravenous vasopressin or saline placebo. Vasopressin (0.1 U/min) increased mean arterial pressure (57+/-4 to 84+/-2 mm Hg, P<.001) and systemic vascular resistance (813+/-113 to 1188+/-87 dyne-s/cm5, P<.001), with decreased norepinephrine administration. There was no significant response to saline, but in three subjects who crossed over, blinded vasopressin increased mean arterial pressure (69+/-8 to 93+/-4 mm Hg) and systemic vascular resistance (898+/-88 to 1443+/-72 dyne-s/cm5) with decreased norepinephrine administration. Plasma vasopressin concentrations prior to randomization clustered in two groups: one (n=5) with concentrations inappropriately low for the degree of hypotension (8.4+/-2.1 pg/mL) and a second (n=3) with moderately elevated levels (33.7+/-1.6 pg/mL); vasopressin increased mean arterial pressure in the low vasopressin group from 57+/-4 to 85+/-2 mm Hg (P<.01) and in the high vasopressin group from 68+/-8 to 86+/-4 mm Hg. CONCLUSIONS: Vasopressin is an effective pressor in vasodilatory shock after cardiopulmonary bypass. An absolute vasopressin deficiency was observed in the majority of patients, but all subjects responded to vasopressin administration.

Arginine Vasopressin↗

Evidence for the microbial basis of a chemoautotrophic invertebrate community at a whale fall on the deep seafloor: bone-colonizing bacteria and invertebrate endosymbionts.

To explore the microbial basis for a remarkable macrofaunal community at the site of a whale skeleton on the seafloor of the Santa Catalina Basin, we obtained samples of whale bone, bone-colonizing invertebrates, microbial mats, and the dominant fauna in the adjacent sulfide-rich sediments during Alvin expeditions in 1988 and 1991. Invertebrate tissues were examined by transmission electron microscopy (TEM) and mats and bone-penetrating bacteria by epifluorescence microscopy (EM). Tissues from the dominant bivalve Vesicomya c.f. gigas, the mytilid mussel Idasola washingtonia, and selected gastropods and limpets were also assayed chemically for enzymes diagnostic of sulfur- and methane-based chemoautotrophy and for stable carbon isotopic composition. Results of all analyses were consistent with dominant sulfur-based endosymbioses in the clam and mussel (the first record of endosymbiosis in the genus Idasola) and the general absence of methane symbioses at the site, strengthening the analogy of the whale-skeleton faunal community to those known from distant Pacific hydrothermal vent sites. Examples of minor endosymbionts, either nitrifying or methanotrophic cells according to internal membrane structures by TEM, raised the possibility of a supplemental mode of nutrition to the clam, or means to remove ammonia in the gill tissue, in the event of significant changes in the chemical environment.

Animals↗

Assessment of transmyocardial perfusion in alligator hearts.

BACKGROUND: Techniques for achieving myocardial perfusion directly from the left ventricular chamber are currently under investigation. Although originally based on the anatomy of reptilian hearts, which are rich in transmural channels and reported to have a poorly developed coronary vasculature, the blood flow capacity of a transmyocardial blood supply has not been studied in these hearts. With the ultimate goal of providing insight into the potential for achieving transmyocardial perfusion in human hearts, we studied the relative contribution of transmyocardial and coronary perfusion in alligator hearts. METHODS AND RESULTS: After explanation from six American alligators, the left ventricle was instrumented, and coronary arteries were perfused with oxygenated physiological solution. Using microspheres to estimate regional myocardial perfusion in the beating hearts, we show that although the epicardium was well perfused by the coronary arteries (0.20 +/- 0.08 versus 0.07 +/- 0.01 mL.min-1.g-1 owing to flow from the ventricular chamber), a significant proportion of endocardial perfusion was from the ventricular chamber (0.21 +/- 0.07 mL.min-1.g-1 from the left ventricle versus 0.13 +/- 0.04 mL.min-1.g-1 from coronary arteries). CONCLUSIONS: A significant amount of direct transmyocardial perfusion is present in alligator hearts. The conditions that apparently permit this situation in reptilian hearts are reviewed, and their implications for aiding in the optimization of techniques for achieving transmyocardial flow in humans are discussed.

Alligators and Crocodiles↗

Sigma 2 receptors as potential biomarkers of proliferation in breast cancer.

sigma 1 and sigma 2 receptors have been shown to exist in a number of rodent and human tumor cell lines. Although their expression is heterogeneous and their function is unknown, sigma receptors have been proposed as potential targets for diagnostic tumor-imaging agents. In this study, the density of sigma 2 receptors in proliferative (P) and quiescent (Q) cells of the mouse mammary adenocarcinoma, line 66, was examined. Scatchard analyses of sigma 2 receptors were performed on membrane preparations of 66 P cells from 3-day cultures and 66 Q cells from 7-, 10-, and 12-day cultures. The Scatchard studies revealed that 66 P cells had approximately 10 times more sigma 2 receptors/cell than the 66 Q cells from 10-day cultures. Although > 97% of the cells were quiescent after 7 days in culture, the maximum differential in the sigma 2 expression between 66 P and 66 Q cells was not attained until these cells had been in culture for 10 days. These data suggest that ligands labeled with positron-emitting or single photon-emitting radionuclides, which selectively bind sigma 2 receptors, have the potential to noninvasively assess the proliferative status of human breast tumors.

Animals↗

Imaging of cholinergic terminals using the radiotracer [18F](+)-4-fluorobenzyltrozamicol: in vitro binding studies and positron emission tomography studies in nonhuman primates.

The goal of the present set of studies was to characterize the in vitro binding properties and in vivo tissue kinetics for the vesicular acetylcholine transporter (VAcChT) radiotracer, [18F](+)-4-fluorobenzyltrozamicol ([18F](+)-FBT). In vitro binding studies were conducted in order to determine the affinity of the (+)- and (-)-stereoisomers of FBT for the VAcChT as well as sigma (sigma 1 and sigma 2) receptors. (+)-FBT was found to have a high affinity (Ki = 0.22 nM) for the VAcChT and lower affinities for sigma 1 (21.6 nM) and sigma 2 (35.9 nM) receptors, whereas (-)-FBT had similar affinities for the VAcChT and sigma 1 receptors (approximately 20 nM) and a lower affinity for sigma 2 (110 nM) receptors. PET imaging studies were conducted in rhesus monkeys (n = 3) with [18F](+)-FBT. [18F](+)-FBT was found to have a high accumulation and slow rate of washout from the basal ganglia, which is consistent with the labeling of cholinergic interneurons in this brain region. [18F](+)-FBT also displayed reversible binding kinetics during the 3 h time course of PET and produced radiolabeled metabolites that did not cross the blood-brain barrier. The results from the current in vitro and in vivo studies indicate that [18F](+)-FBT is a promising ligand for studying cholinergic terminal density, with PET, via the VAcChT.

Animals↗

Blood flow capacity via direct acute myocardial revascularization.

The concept of direct myocardial revascularization, achieving myocardial perfusion through means other than the normal coronary vasculature, has a long history with the most widely investigated technique being the Vineberg procedure; current interest centers around the encouraging preliminary clinical results obtained with transmyocardial laser revascularization. Despite significant previous research, the acute blood flow potential through the direct myocardial route remains unknown. Nontransmural laser channels were made in the distal LAD territory from the epicardial surface of 5 mongrel dogs to which an internal mammary artery was connected. A flow probe was placed on the distal most portion of the artery and an intercostal branch was cannulated for infusion of colored microspheres. Measurements were taken under baseline conditions and following LAD and epicardial collateral ligation. Under all conditions, blood flow pattern was of a to-and-fro nature. At baseline, there was an average 0.60 +/- 0.24 ml/min net flow into the myocardium which was all contained within 0.5 cm of the central channel with a final myocardial perfusion of 0.011 +/- 0.016 ml/min/g. Following induction of ischemia average flow increased to 1.41 +/- 0.51 ml/min which extended as far as 1 cm from the channel with a final myocardial perfusion of 0.22 +/- 0.19 ml/min/g. In conclusion, a limited amount of acute myocardial perfusion can be achieved by the present technique of direct myocardial revascularization and the amount of flow is highly dependent upon the amount of flow through the native circulation.

Animals↗

Physiology, histology, and 2-week morphology of acute transmyocardial channels made with a CO2 laser.

BACKGROUND: Transmyocardial revascularization with a CO2 laser appears to improve symptoms in patients with refractory angina. However, it remains controversial as to whether blood flow through the channels is the mechanism of benefit, especially in the acute setting. METHODS AND RESULTS: Three protocols were used to test whether blood flows through transmyocardial CO2 laser revascularization channels. First, channels were made in excised, cross-perfused dog hearts (n = 5) using a CO2 laser (The Heart Laser; PLC Systems Inc, Milford, MA; 40 J/pulse) followed by ligation of the proximal left anterior descending coronary artery. Colored microspheres injected into the left ventricular chamber failed to detect any significant transmyocardial blood flow. In the second protocol (n = 4), laser channels were created in the left anterior descending artery territory, the left anterior descending artery was ligated, and the hearts were excised after 24 hours. Triphenyltetrazolium chloride staining revealed that no viable myocardium was detected around the laser channels in the ischemic myocardium. Finally, channels examined 2 weeks after creation in normal (n = 6) or ischemic (n = 4) myocardium did not maintain their original caliber but were invaded by granulation tissue, which included a large amount of smaller vascular spaces and vessels of various sizes. CONCLUSIONS: Transmyocardial laser revascularization channels made with this CO2 laser did not provide acute myocardial perfusion or preserve myocardial viability in the face of acute ischemia. Channel morphology changes dramatically within the first 2 weeks. To the degree that these findings pertain to human myocardium, the results suggest that transmyocardial blood flow may not be the mechanism of benefit of this procedure, particularly in the acute setting.

Animals↗

Histologic analysis of transmyocardial channels: comparison of CO2 and holmium:YAG lasers.

BACKGROUND: Transmyocardial laser revascularization using different lasers is being tested in the treatment of refractory angina. We conducted comparative analysis of the acute and chronic myocardial effects of these different lasers. METHODS: Transmyocardial channels were made in normal dog hearts with either a holmium:yttrium-aluminum garnet or a CO2 laser. Channels were examined histologically 6 to 24 hours, 2 to 3 weeks, and 6 weeks after creation. RESULTS: Regardless of the laser source, the channels were occluded by thrombus within 6 to 24 hours. Subsequently, organization and neovascularization of the channel region occurred. Thermoacoustic damage was initially greater with the holmium:yttrium-aluminum garnet laser, but the channel appearances were indistinguishable from those made with the CO2 laser by 6 weeks. CONCLUSIONS: Histologically, the myocardial effects of the CO2 and holmium:yttrium-aluminum garnet lasers are similar and differ predominantly in the amount of acute thermoacoustic injury. Channels are rapidly occluded by thrombus and are replaced by neovascularized collagen. This suggests that the physiologic effects of these two lasers may be similar and that mechanisms other than blood flow through chronic patent channels should be considered as contributing to the clinical benefits observed with this procedure.

Animals↗

Use of positron emission tomography to study the dynamics of psychostimulant-induced dopamine release.

Microdialysis studies have shown that psychostimulants act through a common neurochemical mechanism of elevating synaptic dopamine content in the mesocorticolimbic dopaminergic system. However, little information is available regarding the dynamics of the interaction between the elevated synaptic dopamine levels induced by a psychostimulant and postsynaptic dopamine receptors. The goal of the current investigation was to determine if positron emission tomography (PET) studies using the dopamine D2-selective radioligand [18F]4'-fluoroclebopride ([18F]FCP) could be used to measure synaptic dopamine levels. Rhesus monkeys were used because our previous studies revealed that [18F]FCP has a low test/retest variability in this species. Under control conditions, [18F]FCP had a high uptake and slow rate of washout from the basal ganglia, a region of brain that expresses a high density of D2 receptors, reaching kinetic equilibrium at approximately 40 min. Challenge studies, each separated by at least 1 month, were conducted by administering an intravenous dose of (-)cocaine, d-amphetamine, methylphenidate, or d-methamphetamine (1.0 mg/kg) at 40 min post-IV injection of a no-carrier-added dose of [18F]FCP. In each case, the psychostimulant caused an increase in the rate of washout of [18F]FCP from the basal ganglia. Methamphetamine and amphetamine had more pronounced effects on the washout kinetics of [18F]FCP relative to cocaine and methylphenidate, a result that is consistent with the ability of each drug to elevate synaptic dopamine levels. Our results indicate that challenge studies with [18F]FCP may be a useful technique for studying the dynamics of the interaction between psychostimulant-induced increases in synaptic dopamine and postsynaptic D2 receptors.

Animals↗

Late pulmonary venous complications after lung transplantation.

Although abnormalities of the pulmonary venous anastomosis in the early postoperative period after lung transplantation have been reported from several centers, late complications related to the pulmonary venous anastomosis have not been described. In the present study, we describe the clinical and transesophageal echocardiographic findings of pulmonary vein anastomotic complications in two patients at 1.9 and 2.3 years after lung transplantation. Both pulmonary venous abnormalities, stenosis in the first instance and thrombosis in the second instance, impaired venous outflow on the affected side causing unilateral edema and pleural effusion. Pulmonary venous abnormalities late after lung transplantation can mimic allograft rejection, opportunistic infection, or heart failure and are best diagnosed by transesophageal echocardiography.

Anastomosis, Surgical↗

Angiogenesis: a possible mechanism underlying the clinical benefits of transmyocardial laser revascularization.

While clinical reports indicate that significant relief of angina is achieved with transmyocardial laser revascularization (TMLR), the mechanisms of benefit are still a matter of considerable controversy. Studies in our laboratory, as well as in the laboratories of other investigators, have challenged the classic hypothesis that benefits are derived from blood flow through chronically patent channels. While several alternatives have been proposed, our work has focused on investigating the possibility that TMLR stimulates vascular growth in the region around the TMLR channels. We have performed studies looking at histologic markers of vascular growth (including vessel counting and cellular proliferation assays) in order to test this hypothesis, the results of which are reviewed. In brief, we find that TMLR markedly enhances myocardial vascular growth above what is seen normally in ischemic myocardium. We hypothesize that the underlying mechanism relates to liberation of growth factors by inflammatory cells, which are recruited in response to the laser induced myocardial injury. Clarification of whether this mechanism contributes to observed clinical benefits is of fundamental importance, since such understanding may suggest means of enhancing the process.

Animals↗

Cockroach: the omnivorous scavenger. Potential misinterpretation of postmortem injuries.

Interpretation of postmortem injuries, including their differentiation from those produced antemortem, may be difficult even for experienced forensic pathologists. A variety of animals or insects residing in the death environment may alter the appearance of the deceased. Dictyoptera blattaria (the cockroach) is common in the residential setting. Three cases of sudden and unexpected infant death are presented in which postmortem injuries inflicted by cockroaches initially raised concern of nonaccidental injury. The true nature of the lesions was not recognized by the people at the death scene and, in one case, observation of neck injuries raised suspicion of possible strangulation. In another, the lesions were thought to be burns of different ages. Cockroaches are omnivorous scavengers that devour keratin. They will bite human flesh in both the living and dead with resultant injury. Recognition of cockroach bites will help in the evaluation of injuries discovered during child death investigations.

Animals↗

Amoxycillin as an alternative to dihydrostreptomycin sulphate for treating cattle infected with Leptospira borgpetersenii serovar hardjo.

OBJECTIVE: To assess the effect of amoxycillin treatment on urinary excretion of leptospires from cattle infected with Leptospira borgpetersenii serovar hardjo. DESIGN: A chemotherapy trial with controls. PROCEDURE: Fourteen heifers serologically negative to L hardjo were inoculated with L hardjo via the conjunctival route and assessed for evidence of infection by serological, fluorescent antibody and microbiological tests. Two injections (48 h apart) of amoxycillin at a dose of 15 mg/kg were administered intramuscularly to seven heifers 6.5 weeks after infection; the remaining heifers acted as untreated controls. Later, these seven control group heifers were treated with a single dose of amoxycillin (15 mg/kg). Samples of urine were collected before and after amoxycillin treatments; kidneys were collected at slaughter, and examined by fluorescent antibody test and microbiological culture. RESULTS: Leptospires were isolated from the urine of 11 of 14 heifers inoculated with L hardjo. After treatment of six of these with two injections of amoxycillin, leptospires were not isolated. Of the controls, four of the five initially leptospiruric heifers continued to shed leptospires; after a single injection of amoxycillin, no leptospires were detected in the kidneys of these four. CONCLUSION: Amoxycillin may be an acceptable alternative to dihydrostreptomycin sulphate for the treatment of cattle infected with L hardjo.

Amoxicillin↗