Biomedical subjects

C R Smith

Publications and source records attributed to C R Smith.

At least 55 records · Page 3Linked to original sources

PubMed1999

Cardiac transplantation in a patient with protein S deficiency.

Cardiac transplantation was successfully performed in a patient with end-stage ischemic cardiomyopathy and hereditary protein S deficiency who had undergone two previous coronary artery bypass graft procedures. Routine intraoperative heparinization and reversal with protamine was undertaken, and the antifibrinolytic agent aprotinin was infused throughout the procedure without perioperative hemorrhage or thrombosis. Systemic anticoagulation with intravenous heparin was resumed on postoperative day 2, and the patient was then converted to Lovenex as outpatient anticoagulation to facilitate routine surveillance endomyocardial biopsies.

Anticoagulants↗

PubMed1999

A randomized double-blind study of the effect of triiodothyronine on cardiac function and morbidity after coronary bypass surgery.

BACKGROUND: Although triiodothyronine deficiency has been described after cardiopulmonary bypass, data supporting its use have been conflicting. A double-blind, randomized, placebo-controlled study was undertaken to further define the effect of triiodothyronine on hemodynamics and outcome after coronary artery bypass grafting. METHODS: A total of 170 patients undergoing elective coronary artery bypass grafting were enrolled and completed the study from November 1996 through March 1998. On removal of the aortic crossclamp, patients were randomized to receive either intravenous triiodothyronine (0.4 microgram/kg bolus plus 0.1 microgram/kg infusion administered over a 6-hour period, n = 81) or placebo (n = 89). Outcome variables included hemodynamic profile and inotropic drug/pressor requirements at several time points (mean +/- standard error of the mean), perioperative morbidity (arrhythmia/ischemia/infarction), and mortality. RESULTS: Despite similar baseline characteristics, patients randomized to triiodothyronine had a higher cardiac index and lower inotropic requirements after the operation. Subjects receiving triiodothyronine demonstrated a significantly lower incidence of postoperative myocardial ischemia (4% vs 18%, P =.007) and pacemaker dependence (14% vs 25%, P =.013). Seven patients in the placebo group required postoperative mechanical assistance (intra-aortic balloon pump, n = 4; left ventricular assist device, n = 3), compared with none in the triiodothyronine group (P =.01). There were 2 deaths in the placebo group and no deaths in the triiodothyronine group. CONCLUSIONS: Parenteral triiodothyronine given after crossclamp removal during elective coronary artery bypass grafting significantly improved postoperative ventricular function, reduced the need for treatment with inotropic agents and mechanical devices, and decreased the incidence of myocardial ischemia. The incidence of atrial fibrillation was slightly decreased, and the need for postoperative pacemaker support was reduced.

Aged↗

PubMed1999

Long-term survival after cardiac retransplantation: a twenty-year single-center experience.

OBJECTIVE: To identify risk factors for survival after cardiac retransplantation and compare the survival after retransplantation with that after primary cardiac transplantation. METHODS: A retrospective analysis of 952 patients undergoing cardiac transplantation for the treatment of end-stage heart disease at a single center between 1977 and October 1997. Of these, 43 patients (4.5%) underwent cardiac retransplantation for cardiac failure resulting from transplant-related coronary artery disease, rejection, and early graft failure. RESULTS: No significant difference in actuarial patient survival was found by Kaplan-Meier analysis at 1, 2, and 5 years between patients undergoing primary transplantation and those undergoing retransplantation 76%, 71%, and 60% versus 66%, 66%, and 51%, respectively (P =.2). Multivariable analysis identified a shorter interval between transplants and an initial diagnosis of ischemic cardiomyopathy as significant risk factors for death after retransplantation (P =.04 and.03, respectively). Since 1993, when our criteria for patient selection for retransplantation were revised on the basis of earlier experience to exclude patients with allograft dysfunction as a result of primary graft failure and those with intractable acute rejection occurring less than 6 months after transplantation, the survival has been significantly better (<1993 = 45%, 45%, and 33% versus >/=1993 = 94%, 94%, and 94% at 1, 2, and 4 years, respectively, P =.003). CONCLUSION: The long-term outcome of cardiac retransplantation is comparable with that of primary transplantation, especially in patients with transplant-related coronary artery disease. Patient characteristics and other preoperative variables should assist in the rational application of retransplantation to ensure optimal use of donor organs.

Actuarial Analysis↗

PubMed1999

(+)-p-([18F]fluorobenzyl)spirotrozamicol [(+)-[18F]spiro-FBT]: synthesis and biological evaluation of a high-affinity ligand for the vesicular acetylcholine transporter (VAChT).

(+)-1'-[4-Hydroxy-1-(4-fluorobenzyl)piperidin-3-yl]spiro[1H- indene-1,4'- piperidine] {(+)-Spiro-FBT}, a high-affinity vesicular acetylcholine transporter ligand, was labeled with fluorine-18, and evaluated in the rat and monkey. In the rat brain, (+)-[18F]Spiro-FBT accumulated preferentially in the striatum, hippocampus, and cortex, brains regions containing high-to-moderate densities of cholinergic terminals. However, due to rapid metabolism, no preferential accumulation of the radiotracer was observed in corresponding regions of the monkey brain. Consequently, rapid metabolism renders (+)-[18F]Spiro-FBT unsuitable for studying cholinergic function with positron emission tomography.

Acetylcholine↗

PubMed1999

Arginine vasopressin in the management of vasodilatory hypotension after cardiac transplantation.

Vasodilatory hypotension requiring the administration of catecholamine pressors may occur following cardiopulmonary bypass. We investigated the hemodynamic response to arginine vasopressin (AVP) in 20 patients who developed vasodilatory hypotension after cardiac transplantation. In this cohort, AVP infusion (0.1 U/min) significantly increased mean arterial pressure and decreased norepinephrine requirements, allowing rapid discontinuation of norepinephrine infusions in 7 patients. Judicious use of this novel agent in appropriately selected patients may minimize end-organ sequelae of hypotension and high-dose catecholamine therapy.

Arginine Vasopressin↗

PubMed1999

Polychlorinated biphenyls (PCBs) selectively disrupt serotonergic cell growth in the developing Spisula embryo.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that exert neurotoxic effects during embryonic development. The present study demonstrates that early embryonic exposure to a mixture of PCBs (Aroclor 1254) results in a decrease in serotonergic cell growth. Using a novel, marine invertebrate embryo model, Spisula solidissima, immunocytochemistry, and confocal microscopy techniques, a dose-dependent decrease in serotonergic cell number was quantified within 24 h of exposure. This effect was seen with doses as low as 1 ppm Aroclor 1254. These findings demonstrate that environmentally relevant doses of Aroclor 1254 impair development of the serotonergic nervous system.

Animals↗

PubMed1999

Classification system for complete edentulism. The American College of Prosthodontics.

The American College of Prosthodontists has developed a classification system for complete edentulism based on diagnostic findings. These guidelines may help practitioners determine appropriate treatments for their patients. Four categories are defined, ranging from Class I to Class IV, with Class I representing an uncomplicated clinical situation and a Class IV patient representing the most complex and higher-risk situation. Each class is differentiated by specific diagnostic criteria. This system is designed for use by dental professionals who are involved in the diagnosis of patients requiring treatment for complete edentulism. Potential benefits of the system include: 1) better patient care, 2) improved professional communication, 3) more appropriate insurance reimbursement, 4) a better screening tool to assist dental school admission clinics, and 5) standardized criteria for outcomes assessment.

Alveolar Bone Loss↗

PubMed1999

A profile of multiple sclerosis: the New York State Multiple Sclerosis Consortium.

We have obtained a current profile of multiple sclerosis York State through a centralized patient registry and standardized data collection instrument associated with the New York State Multiple Sclerosis Consortium of 12 MS centers located throughout the state. Data from the first 3019 patients with clinically definite MS revealed a clear relationship between MS disease type, duration of disease, and severity of physical disability. Patients with relapsing disease had disease durations approximately half as long as those with progressive forms of the disease (means approximately 6 years versus 11 years). The majority of patients with relapsing disease had Expanded Disability Status Scale (EDSS) scores of 4.0 or less (self-sustained, fully ambulatory), whereas the majority of patients with progressive disease types had EDSS scores of 6.0 or greater (at least unilateral assist for walking). These findings emphasize the importance of early intervention in patients with relapsing disease to slow or prevent the accumulation of physical disability associated with progressive types of disease. Progressive disease was associated with lack of full-time employment and being disabled before the age of 60 years. Patients with relapsing disease were more likely to be employed and have private forms of insurance, whereas patients with progressive types of disease were more likely to have government-supported insurance to cover medical expenses.

Adult↗

PubMed1999

Experimental and field evaluations of two acaracides for control of I. pacificus (Acari: Ixodidae) in northern California.

Use of acaricides for the control of Ixodes pacificus (Cooley & Kohls), the vector of Lyme borreliosis in the western United States, can be a beneficial component in a program to reduce the morbidity of Lyme borreliosis in California. Three commercially available acaricides, carbaryl, chlorpyrifos, and diazinon, were evaluated in laboratory bioassays for their effectiveness against I. pacificus adults. Based on bioassay results, chlorpyrifos and carbaryl were selected for field evaluations. Chlorpyrifos demonstrated the lowest LD50 in the laboratory and the best overall control in the field trials. Chlorpyrifos and carbaryl provided effective control with a residual effect on adult ticks up to 7 wk after a single treatment. A field application timed to coincide with the highest period of adult questing activity proved effective in the control of I. pacificus in a Sierran foothill habitat. Judicious use of either of the acaricides evaluated may help to reduce adult tick densities in a peridomestic environment and thereby reduce the risk of human exposure to Lyme borreliosis and other tick-borne agents.

Animals↗

PubMed1998

Evidence for unconscious memory processing during elective cardiac surgery.

BACKGROUND: Many anesthetic drugs have been shown to disrupt conscious recall (explicit memory) in volunteers. However, unconscious processing (implicit memory) of intraoperative auditory material may occur during general anesthesia and may provide an opportunity for intraoperative therapeutic intervention. In this study, we examined patients undergoing elective cardiac surgery for evidence of intraoperative implicit and explicit memory. METHODS AND RESULTS: Twenty-five subjects provided written informed consent and underwent general anesthesia and cardiopulmonary bypass for cardiac surgery. During the operation, patients were randomized to receive 1 of 2 different audiotapes of associated word pairs. Postoperatively, a blinded observer conducted a standardized interview to determine the extent of intraoperative implicit and explicit memory. With the use of free association, significant intraoperative implicit memory was found. In contrast, no patient had spontaneous or directed recall of intraoperative events, and we did not find evidence of intraoperative explicit memory with a recognition task. CONCLUSIONS: Patients undergoing general anesthesia for cardiac surgery were reliably able to reinforce associations between word pairs solely on the basis of their intraoperative presentation. This provides further evidence that patients are capable of processing intraoperative auditory information.

Adult↗

PubMed1998

Skeletal dysplasias with gracile bones: three new cases, including two offspring of a mother with a dwarfing condition.

We describe 3 new cases of a rare form of dwarfism (so-called "lethal skeletal dysplasia with gracile bones" or "osteocraniostenosis"), a condition characterized by thin, brittle bones and death in late gestation or early neonatal life. The first was a 37-week gestation female who died at delivery. She had facial anomalies and positional abnormalities of the hands and feet. The others were male stillborn sibs, who died in utero in the third trimester. Their mother had an undiagnosed dwarfing condition associated with body asymmetry, microcephaly, and unusual facial appearance. Both fetuses were documented by ultrasound to have short limbs and probable long bone fractures late in the second trimester. At autopsy, one fetus had no spleen and the other a hypoplastic spleen. Radiographically, all three cases had very thin diaphyses, diaphyseal fractures, and thin ribs and clavicles. In contrast to the first case who had a normally mineralized calvaria, the sibs had grossly deficient calvarial mineralization. Microscopically, endochondral ossification was qualitatively normal but quantitatively deficient in all three cases. The long bones, especially those of the sibs, lacked the well-defined outer cortex in the mid-shaft normally seen by the third trimester. This failure of organization into the cortex and medulla suggests a failure of bone remodelling. Given the variable presentation in these cases, "lethal skeletal dysplasia with gracile bones" is probably a heterogeneous disorder. The recurrence in one family suggests that the mother has somatic/germline mosaicism of a lethal gene, expressed clinically as growth failure and asymmetry.

Adult↗

PubMed1998

Axonal injury and the neuropathology of shaken baby syndrome.

We examined an autopsy series of 14 children with shaken baby syndrome (SBS) who lacked skull fracture. Evidence of axonal injury was sought using immunohistochemical stains for neurofilament, 68-kDa neurofilament and beta-amyloid precursor protein (betaAPP). BetaAPP-positive axons were present in the cerebral white matter of all cases of SBS but were also present in 6 of 7 children dying of non-traumatic hypoxic ischemic encephalopathy (HIE). Swollen axons were present in 11 of 14 cases of SBS and in 6 of 7 cases of HIE. BetaAPP-positive axons were present in both groups in the midbrain and medulla. The cervical spinal cord in SBS contained betaAPP-positive axons in 7 of 11 cases; 5 of 7 contained swollen axons within the white matter tracts; in 2 immunoreactivity was localized to spinal nerve roots; in all 7 there was a predilection for staining at the glial head of the nerve root. Among cases of HIE, none showed abnormal axons or betaAPP-positive reactivity in the cervical cord white matter. We conclude that cerebral axonal injury is common in SBS, and may be due in part to hypoxic/ischemic injury. Cervical cord injury is also common, and cannot be attributed to HIE. These findings corroborate suggestions that flexion-extension injury about the cervical spinal column may be important in the pathogenesis of SBS.

Amyloid beta-Protein Precursor↗

PubMed1998

Randomized, double-blind trial of inhaled nitric oxide in LVAD recipients with pulmonary hypertension.

BACKGROUND: Pulmonary vascular resistance is often elevated in patients with congestive heart failure, and in those undergoing left ventricular assist device (LVAD) insertion, it may precipitate right ventricular failure and hemodynamic collapse. Because the effectiveness of inotropic and vasodilatory agents is limited by systemic effects, right ventricular assist devices are often required. Inhaled nitric oxide (NO) is an effective, specific pulmonary vasodilator that has been used successfully in the management of pulmonary hypertension. METHODS: Eleven of 23 patients undergoing LVAD insertion met criteria for elevated pulmonary vascular resistance on weaning from cardiopulmonary bypass (mean pulmonary artery pressure > 25 mm Hg and LVAD flow rate < 2.5 L x min[-1] x m[-2]) and were randomized to receive either inhaled NO at 20 ppm (n = 6) or nitrogen (n = 5). Patients not manifesting a clinical response after 15 minutes were given the alternative agent. RESULTS: Hemodynamics for the group at randomization were as follows: mean arterial pressure, 72 +/- 6 mm Hg; mean pulmonary artery pressure, 32 +/- 4 mm Hg; and LVAD flow, 2.0 +/- 0.3 L x min(-1) x m(-2). Patients receiving inhaled NO exhibited significant reductions in mean pulmonary artery pressure and increases in LVAD flow, whereas none of the patients receiving nitrogen showed hemodynamic improvement. Further, when the nitrogen group was subsequently given inhaled NO, significant hemodynamic improvements ensued. There were no significant changes in mean arterial pressure in either group. CONCLUSIONS: Inhaled NO induces significant reductions in mean pulmonary artery pressure and increases in LVAD flow in LVAD recipients with elevated pulmonary vascular resistance. We conclude that inhaled NO is a useful intraoperative adjunct in patients undergoing LVAD insertion in whom pulmonary hypertension limits device filling and output.

Administration, Inhalation↗

PubMed1998

Management of bleeding complications in redo cardiac operations.

Bleeding remains a complication of certain complex surgical procedures, particularly those cardiac operations associated with long bypass times and profound hypothermia. Clinical and novel experimental strategies to reduce bleeding and the need for blood and blood-product transfusions are the focus of this review. Preoperative assessment of the patient will identify drug-induced, acquired, or inherited coagulation defects that may contribute to this problem. The main attention is directed to the perioperative period, and broad areas discussed include the preoperative use of erythropoietin to increase red blood cell mass, autologous donation either preoperatively or before bypass, autotransfusion/hemofiltration, and acceptance of relative anemia both during the operation and into the postoperative period. A further, often overlooked, management strategy in treating major coagulopathies is the consideration of the cost and half-lives of the coagulation factors in individual blood components. Prevention of bleeding has become possible both by manipulation of the control of coagulation and inflammatory processes and by the introduction of pharmacologic agents such as aprotinin. Aprotinin is widely used and has proven efficacy in the management of excess bleeding. It is a serine protease inhibitor and has several possible mechanisms of action, including inhibition of the plasma enzyme systems activated by contact with the foreign surface of the bypass circuit and preservation of platelet function. Safety issues include the possibility of hypersensitivity and anaphylactic reaction on a second exposure. Concerns that aprotinin may induce a prothrombotic or coagulant state have no basis in theory or any good evidence in the current literature. A recent study specifically sought to identify the presence of disseminated microvascular platelet-fibrin thrombi present at autopsy in patients who had received aprotinin therapy. The study concluded that diffuse platelet-fibrin thrombi were not a direct complication of aprotinin therapy. Finally, modern molecular biology has led to the recent development of an inhibitor for factor IXa that competitively replaced IXa in the intrinsic complex and blocked the conversion of factor X to factor Xa. This compound is under investigation in animal studies. These have so far shown efficacy in reducing blood loss after bypass in comparison with standard heparin anticoagulation.

Aprotinin↗

PubMed1998

Evidence of vascular growth associated with laser treatment of normal canine myocardium.

BACKGROUND: Transmyocardial laser revascularization is a new therapy for patients with refractory angina. Although clinical studies suggest that transmyocardial laser revascularization decreases angina and may improve regional blood flow, the underlying mechanisms are not elucidated. We hypothesized that one mechanism may relate to stimulation of vascular growth in laser-treated regions. METHODS: Transmyocardial laser revascularization channels were made with holmium:yttrium-aluminum garnet or carbon dioxide lasers in eight normal canine hearts; animals were sacrificed 2 to 3 weeks later and examined for vascular density and for evidence of smooth muscle proliferation. RESULTS: The original channels were infiltrated by granulation tissue with associated vascularity. Vascular growth was stimulated immediately surrounding the channel remnant as evidenced by an increase in the number of vessels (approximately twice that of the control region) and an increase in the number of vascular cells staining positive for markers of cellular proliferation. CONCLUSIONS: Transmyocardial laser revascularization leads to local vascular growth as early as 2 weeks after treatment. It remains to be determined whether this mechanism contributes to increased regional blood flow or to clinical benefits associated with this novel form of therapy.

Aluminum Silicates↗

PubMed1998

Management of vasodilatory shock after cardiac surgery: identification of predisposing factors and use of a novel pressor agent.

BACKGROUND: Cardiopulmonary bypass can be associated with vasodilatory hypotension requiring pressor support. We have previously found arginine vasopressin to be a remarkably effective pressor in a variety of vasodilatory shock states. We investigated the incidence and clinical predictors of vasodilatory shock in a general population of cardiac surgical patients and the effects of low-dose arginine vasopressin as treatment of this syndrome in patients with heart failure. METHODS: Patients undergoing cardiopulmonary bypass (n = 145) were studied prospectively. Preoperative ejection fraction, medications, and perioperative hemodynamics were recorded, and postbypass serum arginine vasopressin levels were measured. Vasodilatory shock was defined as a mean arterial pressure lower than 70 mm Hg, a cardiac index greater than 2.5 L/min/m2, and norepinephrine dependence. Predictors of vasodilatory shock were investigated by logistic regression analysis. The hemodynamic responses of patients who received arginine vasopressin infusions for vasodilatory shock after cardiopulmonary bypass for left ventricular assist device placement or heart transplantation were analyzed retrospectively. RESULTS: Eleven of 145 general cardiac surgery patients (8%) met criteria for postbypass vasodilatory shock. By multivariate analysis, an ejection fraction lower than 0.35 and angiotensin-converting enzyme inhibitor use were independent predictors of postbypass vasodilatory shock (relative risks of 9.1 and 11.9, respectively). Vasodilatory shock was associated with inappropriately low serum arginine vasopressin concentrations (12.0 +/- 6.6 pg/mL). Retrospective analysis found 40 patients with postbypass vasodilatory shock who received low-dose arginine vasopressin infusions, resulting in increased mean arterial pressure and decreased norepinephrine requirements. CONCLUSIONS: Low ejection fraction and angiotensin-converting enzyme inhibitor use are risk factors for postbypass vasodilatory shock, and this syndrome is associated with vasopressin deficiency. In patients exhibiting this syndrome after high-risk cardiac operations, replacement of arginine vasopressin increases blood pressure and reduces catecholamine pressor requirements.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Angiogenesis is enhanced in ischemic canine myocardium by transmyocardial laser revascularization.

OBJECTIVES: This study sought to test whether transmyocardial laser revascularization (TMLR) stimulates angiogenesis in an animal model of chronic ischemia. BACKGROUND: TMLR relieves angina and may also improve blood flow in patients who are not candidates for traditional therapies. The mechanisms of these benefits are not fully defined. METHODS: Ischemia was created in 14 dogs by proximal left anterior descending coronary ameroid constrictors. TMLR was performed in the anterior wall (approximately 1 channel/cm2) of seven dogs; the remaining dogs served as the ischemic control group. Myocardial blood flow was measured (colored microspheres) at rest and during chemical stress (adenosine) in the acute setting and after 2 months. RESULTS: TMLR did not influence blood flow in the acute setting. After 2 months, resting blood flow increased comparably in the anterior wall in both groups to approximately 80% of normal. However, the TMLR-treated dogs demonstrated an approximately 40% increase in blood flow capacity during stress in the ischemic territory compared with untreated dogs (left anterior descending coronary artery/left circumflex coronary artery flow 0.53+/-0.16 in the control group vs. 0.73+/-0.08 in TMLR animals, p < 0.05). Vascular proliferation, assessed by bromodeoxyuridine incorporation and proliferating cell nuclear antigen positivity in endothelial and smooth muscle cells was about four times greater in the TMLR group than in the control group (p < 0.001). The density of vessels with at least one smooth muscle cell layer was approximately 1.4 times greater in the myocardium surrounding the TMLR channel remnants than in control ischemic tissue (p < 0.001). CONCLUSIONS: In this canine model of chronic ischemia, TMLR significantly enhances angiogenesis as evidenced by the increased number of vessels lined with smooth muscle cells, markedly increased vascular proliferation and increased blood flow capacity during stress.

Angioplasty, Balloon, Laser-Assisted↗

PubMed1998

Cost-effectiveness of coronary artery bypass surgery in octogenarians.

OBJECTIVE: The objective of this retrospective cohort study was to determine whether coronary artery bypass graft (CABG) surgery is effective and cost-effective relative to medical management of coronary artery disease (CAD) in the elderly. SUMMARY BACKGROUND DATA: The aging of the U.S population and the improvements in surgical techniques have resulted in increasing numbers of elderly patients who undergo this surgery. The three randomized, controlled trials (RCTs) that established the efficacy of CABG surgery completed patient enrollment from 19 to 24 years ago excluded patients older than 65 years. Although information regarding outcomes of CABG in this population is mainly available in case series, a major lacuna exists with respect to information on quality of life and cost effectiveness of surgery as compared with medical management. METHODS: The authors retrospectively formed surgical and medically managed cohorts of octogenarians with significant multivessel CAD. More than 600 medical records of patients older than 80 years who underwent angiography at our institution were reviewed to identify 48 patients who were considered reasonable surgical candidates but had not undergone surgery. This cohort was compared with 176 patients who underwent surgery. RESULTS: The cost per quality-adjusted life year saved was $10,424. At 3 years, survival in the surgical group was 80% as compared with 64% in the entire medical cohort and 50% in a smaller subset of the medical cohort. Quality of life in patients who underwent surgery was measurably better than that of the medical cohort with utility index scores, as measured by the EuroQoL, (a seven-item quality of life questionnaire) of 0.84, 0.61, and 0.74, respectively. CONCLUSIONS: Performing CABG surgery in octogenarians is highly cost-effective. The quality of life of the elderly who elect to undergo CABG surgery is greater than that of their cohorts and equal to that of an average 55-year-old person in the general population.

Age Factors↗